Role of Prefrontal Persistent Activity in Working Memory

PubMed Central

Riley, Mitchell R.; Constantinidis, Christos

2016-01-01

The prefrontal cortex is activated during working memory, as evidenced by fMRI results in human studies and neurophysiological recordings in animal models. Persistent activity during the delay period of working memory tasks, after the offset of stimuli that subjects are required to remember, has traditionally been thought of as the neural correlate of working memory. In the last few years several findings have cast doubt on the role of this activity. By some accounts, activity in other brain areas, such as the primary visual and posterior parietal cortex, is a better predictor of information maintained in visual working memory and working memory performance; dynamic patterns of activity may convey information without requiring persistent activity at all; and prefrontal neurons may be ill-suited to represent non-spatial information about the features and identity of remembered stimuli. Alternative interpretations about the role of the prefrontal cortex have thus been suggested, such as that it provides a top-down control of information represented in other brain areas, rather than maintaining a working memory trace itself. Here we review evidence for and against the role of prefrontal persistent activity, with a focus on visual neurophysiology. We show that persistent activity predicts behavioral parameters precisely in working memory tasks. We illustrate that prefrontal cortex represents features of stimuli other than their spatial location, and that this information is largely absent from early cortical areas during working memory. We examine memory models not dependent on persistent activity, and conclude that each of those models could mediate only a limited range of memory-dependent behaviors. We review activity decoded from brain areas other than the prefrontal cortex during working memory and demonstrate that these areas alone cannot mediate working memory maintenance, particularly in the presence of distractors. We finally discuss the discrepancy between BOLD activation and spiking activity findings, and point out that fMRI methods do not currently have the spatial resolution necessary to decode information within the prefrontal cortex, which is likely organized at the micrometer scale. Therefore, we make the case that prefrontal persistent activity is both necessary and sufficient for the maintenance of information in working memory. PMID:26778980

Prefrontal Reactivity to Social Signals of Threat as a Predictor of Treatment Response in Anxious Youth

PubMed Central

Kujawa, Autumn; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

2016-01-01

Neuroimaging has shown promise as a tool to predict likelihood of treatment response in adult anxiety disorders, with potential implications for clinical decision-making. Despite the relatively high prevalence and emergence of anxiety disorders in youth, very little work has evaluated neural predictors of response to treatment. The goal of the current study was to examine brain function during emotional face processing as a predictor of response to treatment in children and adolescents (age 7–19 years; N=41) with generalized, social, and/or separation anxiety disorder. Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), participants completed an emotional faces matching task during functional magnetic resonance imaging (fMRI). Whole brain responses to threatening (ie, angry and fearful) and happy faces were examined as predictors of change in anxiety severity following treatment. Greater activation in inferior and superior frontal gyri, including dorsolateral prefrontal cortex and ventrolateral prefrontal cortex, as well as precentral/postcentral gyri during processing of threatening faces predicted greater response to CBT and SSRI treatment. For processing of happy faces, activation in postcentral gyrus was a significant predictor of treatment response. Post-hoc analyses indicated that effects were not significantly moderated by type of treatment. Findings suggest that greater activation in prefrontal regions involved in appraising and regulating responses to social signals of threat predict better response to SSRI and CBT treatment in anxious youth and that neuroimaging may be a useful tool for predicting how youth will respond to treatment. PMID:26708107

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

PubMed

Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

Neural Mechanisms of Grief Regulation

PubMed Central

Freed, Peter J.; Yanagihara, Ted K.; Hirsch, Joy; Mann, J. John

2009-01-01

Background: The death of an attachment figure triggers intrusive thoughts of the deceased, sadness, and yearning for reunion. Recovery requires reduction of symptoms. We hypothesized that symptoms might correlate with a capacity to regulate attention toward reminders of the deceased, and activity in, and functional connectivity between, prefrontal regulatory regions and the amygdala. Methods: Twenty recently bereaved subjects rated intrusive thoughts of the deceased versus a capacity to avoid thoughts (grief style). Reaction time was measured while subjects completed an Emotional Stroop (ES) task contrasting deceased-related with control words during functional magnetic resonance imaging (fMRI). Subjects subsequently visualized the death of the deceased and rated induced emotions. Results: Subjects demonstrated attentional bias toward deceased-related words. Bias magnitude correlated with amygdala, insula, dorsolateral prefrontal cortex (DLPFC) activity. Amygdala activity predicted induced sadness intensity. A double dissociation between grief style and both prefrontal and amygdala subregion activity was found. Intrusiveness correlated with activation of ventral amygdala and rostral anterior cingulate (rACC); avoidance correlated with deactivation of dorsal amygdala and DLPFC. A double dissociation between regulatory region and task-dependent functional connectivity (FC) was found. High DLPFC-amygdala FC correlated with reduced attentional bias, while low rACC-amygdala FC predicted sadness intensity. Conclusions: Results are consistent with a model in which activity in and functional connectivity between the amygdala and prefrontal regulatory regions indexes differences in mourners' regulation of attention and sadness during pangs of grief, and may be used to distinguish between clinically relevant differences in grief style. PMID:19249748

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

PubMed

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

2017-02-01

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

Prefrontal Brain Activity Predicts Temporally Extended Decision-Making Behavior

ERIC Educational Resources Information Center

Yarkoni, Tal; Braver, Todd S.; Gray, Jeremy R.; Green, Leonard

2005-01-01

Although functional neuroimaging studies of human decision-making processes are increasingly common, most of the research in this area has relied on passive tasks that generate little individual variability. Relatively little attention has been paid to the ability of brain activity to predict overt behavior. Using functional magnetic resonance…

Prefrontal Hemodynamic Changes Associated with Subjective Sense of Occlusal Discomfort

PubMed Central

Kobayashi, Goh; Hayama, Rika; Ikuta, Ryuhei; Onozouka, Minoru; Wake, Hiroyuki; Shimada, Atsushi; Shibuya, Tomoaki; Tamaki, Katsushi

2015-01-01

We used functional near-infrared spectroscopy to measure prefrontal brain activity accompanying the physical sensation of oral discomfort that arose when healthy young-adult volunteers performed a grinding motion with mild occlusal elevation (96 μm). We simultaneously evaluated various forms of occlusal discomfort using the visual analogue scale (VAS) and hemodynamic responses to identify the specific prefrontal activity that occurs with increased occlusal discomfort. The Oxy-Hb responses of selected channels in the bilateral frontopolar and dorsolateral prefrontal cortices increased in participants who reported increased severity of occlusal discomfort, while they decreased in those who reported no change or decreased occlusal discomfort during grinding. Moreover, the cumulative values of Oxy-Hb response in some of these channels were statistically significant predictive factors for the VAS scores. A generalized linear model analysis of Oxy-Hb signals in a group of participants who reported increased discomfort further indicated significant cerebral activation in the right frontopolar and dorsolateral prefrontal cortices that overlapped with the results of correlation analyses. Our results suggest that the increased hemodynamic responses in the prefrontal area reflect the top-down control of attention and/or self-regulation against the uncomfortable somatosensory input, which could be a possible marker to detect the subjective sense of occlusal discomfort. PMID:26090407

Medial prefrontal cortex supports source memory accuracy for self-referenced items

PubMed Central

Leshikar, Eric D.; Duarte, Audrey

2013-01-01

Previous behavioral work suggests that processing information in relation to the self enhances subsequent item recognition. Neuroimaging evidence further suggests that regions along the cortical midline, particularly those of the medial prefrontal cortex, underlie this benefit. There has been little work to date, however, on the effects of self-referential encoding on source memory accuracy or whether the medial prefrontal cortex might contribute to source memory for self-referenced materials. In the current study, we used fMRI to measure neural activity while participants studied and subsequently retrieved pictures of common objects superimposed on one of two background scenes (sources) under either self-reference or self-external encoding instructions. Both item recognition and source recognition were better for objects encoded self-referentially than self-externally. Neural activity predictive of source accuracy was observed in the medial prefrontal cortex (BA 10) at the time of study for self-referentially but not self-externally encoded objects. The results of this experiment suggest that processing information in relation to the self leads to a mnemonic benefit for source level features, and that activity in the medial prefrontal cortex contributes to this source memory benefit. This evidence expands the purported role that the medial prefrontal cortex plays in self-referencing. PMID:21936739

Idiosyncratic Patterns of Representational Similarity in Prefrontal Cortex Predict Attentional Performance.

PubMed

Lee, Jeongmi; Geng, Joy J

2017-02-01

The efficiency of finding an object in a crowded environment depends largely on the similarity of nontargets to the search target. Models of attention theorize that the similarity is determined by representations stored within an "attentional template" held in working memory. However, the degree to which the contents of the attentional template are individually unique and where those idiosyncratic representations are encoded in the brain are unknown. We investigated this problem using representational similarity analysis of human fMRI data to measure the common and idiosyncratic representations of famous face morphs during an identity categorization task; data from the categorization task were then used to predict performance on a separate identity search task. We hypothesized that the idiosyncratic categorical representations of the continuous face morphs would predict their distractability when searching for each target identity. The results identified that patterns of activation in the lateral prefrontal cortex (LPFC) as well as in face-selective areas in the ventral temporal cortex were highly correlated with the patterns of behavioral categorization of face morphs and search performance that were common across subjects. However, the individually unique components of the categorization behavior were reliably decoded only in right LPFC. Moreover, the neural pattern in right LPFC successfully predicted idiosyncratic variability in search performance, such that reaction times were longer when distractors had a higher probability of being categorized as the target identity. These results suggest that the prefrontal cortex encodes individually unique components of categorical representations that are also present in attentional templates for target search. Everyone's perception of the world is uniquely shaped by personal experiences and preferences. Using functional MRI, we show that individual differences in the categorization of face morphs between two identities could be decoded from the prefrontal cortex and the ventral temporal cortex. Moreover, the individually unique representations in prefrontal cortex predicted idiosyncratic variability in attentional performance when looking for each identity in the "crowd" of another morphed face in a separate search task. Our results reveal that the representation of task-related information in prefrontal cortex is individually unique and preserved across categorization and search performance. This demonstrates the possibility of predicting individual behaviors across tasks with patterns of brain activity. Copyright © 2017 the authors 0270-6474/17/371257-12$15.00/0.

Prefrontal cortex modulates posterior alpha oscillations during top-down guided visual perception

PubMed Central

Helfrich, Randolph F.; Huang, Melody; Wilson, Guy; Knight, Robert T.

2017-01-01

Conscious visual perception is proposed to arise from the selective synchronization of functionally specialized but widely distributed cortical areas. It has been suggested that different frequency bands index distinct canonical computations. Here, we probed visual perception on a fine-grained temporal scale to study the oscillatory dynamics supporting prefrontal-dependent sensory processing. We tested whether a predictive context that was embedded in a rapid visual stream modulated the perception of a subsequent near-threshold target. The rapid stream was presented either rhythmically at 10 Hz, to entrain parietooccipital alpha oscillations, or arrhythmically. We identified a 2- to 4-Hz delta signature that modulated posterior alpha activity and behavior during predictive trials. Importantly, delta-mediated top-down control diminished the behavioral effects of bottom-up alpha entrainment. Simultaneous source-reconstructed EEG and cross-frequency directionality analyses revealed that this delta activity originated from prefrontal areas and modulated posterior alpha power. Taken together, this study presents converging behavioral and electrophysiological evidence for frontal delta-mediated top-down control of posterior alpha activity, selectively facilitating visual perception. PMID:28808023

Prefrontal EEG alpha asymmetry changes while observing disaster happening to other people: cardiac correlates and prediction of emotional impact.

PubMed

Papousek, Ilona; Weiss, Elisabeth M; Schulter, Günter; Fink, Andreas; Reiser, Eva M; Lackner, Helmut K

2014-12-01

Changes of EEG alpha asymmetry in terms of increased right versus left sided activity in prefrontal cortex are considered to index activation of the withdrawal/avoidance motivational system. The present study aimed to add evidence of the validity of individual differences in the EEG alpha asymmetry response and their relevance regarding the impact of emotional events. The magnitude of the EEG alpha asymmetry response while watching a film consisting of scenes of real injury and death correlated with components of transient cardiac responses to sudden horrifying events happening to persons in the film which index withdrawal/avoidance motivation and heightened attention and perceptual intake. Additionally, it predicted greater mood deterioration following the film and film-related intrusive memories and avoidance over the following week. The study provides further evidence for prefrontal EEG alpha asymmetry changes in response to relevant stimuli reflecting an individual's sensitivity to negative social-emotional cues encountered in everyday life. Copyright © 2014 Elsevier B.V. All rights reserved.

Frontolimbic Neural Circuit Changes in Emotional Processing and Inhibitory Control Associated With Clinical Improvement Following Transference-Focused Psychotherapy in Borderline Personality Disorder

PubMed Central

Perez, David L.; Vago, David R.; Pan, Hong; Root, James; Tuescher, Oliver; Fuchs, Benjamin H.; Leung, Lorene; Epstein, Jane; Cain, Nicole M.; Clarkin, John F.; Lenzenweger, Mark F.; Kernberg, Otto F.; Levy, Kenneth N.; Silbersweig, David A.; Stern, Emily

2015-01-01

Aim Borderline personality disorder (BPD) is characterized by self-regulation deficits, including impulsivity and affective lability. Transference-Focused Psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms across multiple cognitive-emotional domains in BPD. This pilot study aims to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP. Methods BPD subjects (N=10) were scanned pre- and post-TFP treatment using a within-subjects design. A disorder-specific emotional-linguistic go/no-go fMRI paradigm was used to probe the interaction between negative emotional processing and inhibitory control. Results Analyses demonstrated significant treatment-related effects with relative increased dorsal prefrontal (dorsal anterior cingulate, dorsolateral prefrontal, and frontopolar cortices) activation, and relative decreased ventrolateral prefrontal cortex and hippocampal activation following treatment. Clinical improvement in constraint correlated positively with relative increased left dorsal anterior cingulate cortex activation. Clinical improvement in affective lability correlated positively with left posterior-medial orbitofrontal cortex/ventral striatum activation, and negatively with right amygdala/parahippocampal activation. Post-treatment improvements in constraint were predicted by pre-treatment right dorsal anterior cingulate cortex hypoactivation, and pre-treatment left posterior-medial orbitofrontal cortex/ventral striatum hypoactivation predicted improvements in affective lability. Conclusions These preliminary findings demonstrate potential TFP-associated alterations in frontolimbic circuitry and begin to identify neural mechanisms associated with a psychodynamically-oriented psychotherapy. PMID:26289141

Prefrontal and parietal activity is modulated by the rule complexity of inductive reasoning and can be predicted by a cognitive model.

PubMed

Jia, Xiuqin; Liang, Peipeng; Shi, Lin; Wang, Defeng; Li, Kuncheng

2015-01-01

In neuroimaging studies, increased task complexity can lead to increased activation in task-specific regions or to activation of additional regions. How the brain adapts to increased rule complexity during inductive reasoning remains unclear. In the current study, three types of problems were created: simple rule induction (i.e., SI, with rule complexity of 1), complex rule induction (i.e., CI, with rule complexity of 2), and perceptual control. Our findings revealed that increased activations accompany increased rule complexity in the right dorsal lateral prefrontal cortex (DLPFC) and medial posterior parietal cortex (precuneus). A cognitive model predicted both the behavioral and brain imaging results. The current findings suggest that neural activity in frontal and parietal regions is modulated by rule complexity, which may shed light on the neural mechanisms of inductive reasoning. Copyright © 2014. Published by Elsevier Ltd.

Persistent neuronal activity in human prefrontal cortex links perception and action

PubMed Central

Haller, Matar; Case, John; Crone, Nathan E.; Chang, Edward F.; King-Stephens, David; Laxer, Kenneth D.; Weber, Peter B.; Parvizi, Josef; Knight, Robert T.; Shestyuk, Avgusta Y.

2017-01-01

How do humans flexibly respond to changing environmental demands on a sub-second temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behavior, yet the core mechanisms that translate sensory information into behavior remain undefined. Utilizing direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity, indexed by the broadband gamma signal, while sixteen participants performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centered in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behavior.

How the brain predicts people's behavior in relation to rules and desires. Evidence of a medio-prefrontal dissociation.

PubMed

Corradi-Dell'Acqua, Corrado; Turri, Francesco; Kaufmann, Laurence; Clément, Fabrice; Schwartz, Sophie

2015-09-01

Forming and updating impressions about others is critical in everyday life and engages portions of the dorsomedial prefrontal cortex (dMPFC), the posterior cingulate cortex (PCC) and the amygdala. Some of these activations are attributed to "mentalizing" functions necessary to represent people's mental states, such as beliefs or desires. Evolutionary psychology and developmental studies, however, suggest that interpersonal inferences can also be obtained through the aid of deontic heuristics, which dictate what must (or must not) be done in given circumstances. We used fMRI and asked 18 participants to predict whether unknown characters would follow their desires or obey external rules. Participants had no means, at the beginning, to make accurate predictions, but slowly learned (throughout the experiment) each character's behavioral profile. We isolated brain regions whose activity changed during the experiment, as a neural signature of impression updating: whereas dMPFC was progressively more involved in predicting characters' behavior in relation to their desires, the medial orbitofrontal cortex and the amygdala were progressively more recruited in predicting rule-based behavior. Our data provide evidence of a neural dissociation between deontic inference and theory-of-mind (ToM), and support a differentiation of orbital and dorsal prefrontal cortex in terms of low- and high-level social cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory.

PubMed

Fazio, Leonardo; Pergola, Giulio; Papalino, Marco; Di Carlo, Pasquale; Monda, Anna; Gelao, Barbara; Amoroso, Nicola; Tangaro, Sabina; Rampino, Antonio; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2018-05-22

Dopamine D 1 receptor (D 1 R) signaling shapes prefrontal cortex (PFC) activity during working memory (WM). Previous reports found higher WM performance associated with alleles linked to greater expression of the gene coding for D 1 Rs ( DRD1 ). However, there is no evidence on the relationship between genetic modulation of DRD1 expression in PFC and patterns of prefrontal activity during WM. Furthermore, previous studies have not considered that D 1 Rs are part of a coregulated molecular environment, which may contribute to D 1 R-related prefrontal WM processing. Thus, we hypothesized a reciprocal link between a coregulated (i.e., coexpressed) molecular network including DRD1 and PFC activity. To explore this relationship, we used three independent postmortem prefrontal mRNA datasets (total n = 404) to characterize a coexpression network including DRD1 Then, we indexed network coexpression using a measure (polygenic coexpression index- DRD1 -PCI) combining the effect of single nucleotide polymorphisms (SNPs) on coexpression. Finally, we associated the DRD1 -PCI with WM performance and related brain activity in independent samples of healthy participants (total n = 371). We identified and replicated a coexpression network including DRD1 , whose coexpression was correlated with DRD1 -PCI. We also found that DRD1 -PCI was associated with lower PFC activity and higher WM performance. Behavioral and imaging results were replicated in independent samples. These findings suggest that genetically predicted expression of DRD1 and of its coexpression partners stratifies healthy individuals in terms of WM performance and related prefrontal activity. They also highlight genes and SNPs potentially relevant to pharmacological trials aimed to test cognitive enhancers modulating DRD1 signaling.

Multi-voxel patterns of visual category representation during episodic encoding are predictive of subsequent memory

PubMed Central

Kuhl, Brice A.; Rissman, Jesse; Wagner, Anthony D.

2012-01-01

Successful encoding of episodic memories is thought to depend on contributions from prefrontal and temporal lobe structures. Neural processes that contribute to successful encoding have been extensively explored through univariate analyses of neuroimaging data that compare mean activity levels elicited during the encoding of events that are subsequently remembered vs. those subsequently forgotten. Here, we applied pattern classification to fMRI data to assess the degree to which distributed patterns of activity within prefrontal and temporal lobe structures elicited during the encoding of word-image pairs were diagnostic of the visual category (Face or Scene) of the encoded image. We then assessed whether representation of category information was predictive of subsequent memory. Classification analyses indicated that temporal lobe structures contained information robustly diagnostic of visual category. Information in prefrontal cortex was less diagnostic of visual category, but was nonetheless associated with highly reliable classifier-based evidence for category representation. Critically, trials associated with greater classifier-based estimates of category representation in temporal and prefrontal regions were associated with a higher probability of subsequent remembering. Finally, consideration of trial-by-trial variance in classifier-based measures of category representation revealed positive correlations between prefrontal and temporal lobe representations, with the strength of these correlations varying as a function of the category of image being encoded. Together, these results indicate that multi-voxel representations of encoded information can provide unique insights into how visual experiences are transformed into episodic memories. PMID:21925190

A functional imaging investigation of moral deliberation and moral intuition

PubMed Central

Harenski, Carla L.; Antonenko, Olga; Shane, Matthew S.; Kiehl, Kent A.

2014-01-01

Prior functional imaging studies of moral processing have utilized ‘explicit’ moral tasks that involve moral deliberation (e.g., reading statements such as ‘he shot the victim’ and rating the moral appropriateness of the behavior) or ‘implicit’ moral tasks that involve moral intuition (e.g., reading similar statements and memorizing them for a test but not rating their moral appropriateness). Although the neural mechanisms underlying moral deliberation and moral intuition may differ, these have not been directly compared. Studies using explicit moral tasks have reported increased activity in several regions, most consistently the medial prefrontal cortex and temporo-parietal junction. In the few studies that have utilized implicit moral tasks, medial prefrontal activity has been less consistent, suggesting the medial prefrontal cortex is more critical for moral deliberation than moral intuition. Thus, we hypothesized that medial prefrontal activity would be increased during an explicit, but not an implicit, moral task. Participants (n = 28) were scanned using fMRI while viewing 50 unpleasant pictures, half of which depicted moral violations. Half of the participants rated pictures on moral violation severity (explicit task) while the other half indicated whether pictures occurred indoors or outdoors (implicit task). As predicted, participants performing the explicit, but not the implicit, task showed increased ventromedial prefrontal activity while viewing moral pictures. Both groups showed increased temporo-parietal junction activity while viewing moral pictures. These results suggest that the ventromedial prefrontal cortex may contribute more to moral deliberation than moral intuition, whereas the temporo-parietal junction may contribute more to moral intuition than moral deliberation. PMID:19878727

PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation.

PubMed

Fonzo, Gregory A; Goodkind, Madeleine S; Oathes, Desmond J; Zaiko, Yevgeniya V; Harvey, Meredith; Peng, Kathy K; Weiss, M Elizabeth; Thompson, Allison L; Zack, Sanno E; Lindley, Steven E; Arnow, Bruce A; Jo, Booil; Gross, James J; Rothbaum, Barbara O; Etkin, Amit

2017-12-01

Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms. At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.

Fine-grained temporal coding of visually-similar categories in the ventral visual pathway and prefrontal cortex

PubMed Central

Xu, Yang; D'Lauro, Christopher; Pyles, John A.; Kass, Robert E.; Tarr, Michael J.

2013-01-01

Humans are remarkably proficient at categorizing visually-similar objects. To better understand the cortical basis of this categorization process, we used magnetoencephalography (MEG) to record neural activity while participants learned–with feedback–to discriminate two highly-similar, novel visual categories. We hypothesized that although prefrontal regions would mediate early category learning, this role would diminish with increasing category familiarity and that regions within the ventral visual pathway would come to play a more prominent role in encoding category-relevant information as learning progressed. Early in learning we observed some degree of categorical discriminability and predictability in both prefrontal cortex and the ventral visual pathway. Predictability improved significantly above chance in the ventral visual pathway over the course of learning with the left inferior temporal and fusiform gyri showing the greatest improvement in predictability between 150 and 250 ms (M200) during category learning. In contrast, there was no comparable increase in discriminability in prefrontal cortex with the only significant post-learning effect being a decrease in predictability in the inferior frontal gyrus between 250 and 350 ms (M300). Thus, the ventral visual pathway appears to encode learned visual categories over the long term. At the same time these results add to our understanding of the cortical origins of previously reported signature temporal components associated with perceptual learning. PMID:24146656

Altered prefrontal brain activity in persons at risk for Alzheimer's disease: an fMRI study.

PubMed

Elgh, Eva; Larsson, Anne; Eriksson, Sture; Nyberg, Lars

2003-06-01

Early diagnosis of Alzheimer's disease (AD) is critical for adequate treatment and care. Recently it has been shown that functional magnetic resonance imaging (fMRI) can be important in preclinical detection of AD. The purpose of this study was to examine possible differences in memory-related brain activation between persons with high versus low risk for AD. This was achieved by combining a validated neurocognitive screening battery (the 7-minutes test) with memory assessment and fMRI. One hundred two healthy community-living persons with subjective memory complaints were recruited through advertisement and tested with the 7-minutes test. Based on their test performance they were classified as having either high (n = 8) or low risk (n = 94) for AD. Six high-risk individuals and six age-, sex-, and education-matched low-risk individuals were investigated with fMRI while engaged in episodic memory tasks. The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences (p < .05 corrected). During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. Patterns of prefrontal brain activity related to episodic memory differ between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.

Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents

PubMed Central

Büchel, Christian; Peters, Jan; Banaschewski, Tobias; Bokde, Arun L. W.; Bromberg, Uli; Conrod, Patricia J.; Flor, Herta; Papadopoulos, Dimitri; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paillère-Martinot, Marie-Laure; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Poustka, Luise; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Gallinat, Juergen; Schumann, Gunter; Knutson, Brian; Arroyo, Mercedes; Artiges, Eric; Aydin, Semiha; Bach, Christine; Barbot, Alexis; Barker, Gareth; Bruehl, Ruediger; Cattrell, Anna; Constant, Patrick; Crombag, Hans; Czech, Katharina; Dalley, Jeffrey; Decideur, Benjamin; Desrivieres, Sylvane; Fadai, Tahmine; Fauth-Buhler, Mira; Feng, Jianfeng; Filippi, Irinia; Frouin, Vincent; Fuchs, Birgit; Gemmeke, Isabel; Genauck, Alexander; Hanratty, Eanna; Heinrichs, Bert; Heym, Nadja; Hubner, Thomas; Ihlenfeld, Albrecht; Ing, Alex; Ireland, James; Jia, Tianye; Jones, Jennifer; Jurk, Sarah; Kaviani, Mehri; Klaassen, Arno; Kruschwitz, Johann; Lalanne, Christophe; Lanzerath, Dirk; Lathrop, Mark; Lawrence, Claire; Lemaitre, Hervé; Macare, Christine; Mallik, Catherine; Mar, Adam; Martinez-Medina, Lourdes; Mennigen, Eva; de Carvahlo, Fabiana Mesquita; Mignon, Xavier; Millenet, Sabina; Miranda, Ruben; Müller, Kathrin; Nymberg, Charlotte; Parchetka, Caroline; Pena-Oliver, Yolanda; Pentilla, Jani; Poline, Jean-Baptiste; Quinlan, Erin Burke; Rapp, Michael; Ripke, Stephan; Ripley, Tamzin; Robert, Gabriel; Rogers, John; Romanowski, Alexander; Ruggeri, Barbara; Schmäl, Christine; Schmidt, Dirk; Schneider, Sophia; Schubert, Florian; Schwartz, Yannick; Sommer, Wolfgang; Spanagel, Rainer; Speiser, Claudia; Spranger, Tade; Stedman, Alicia; Stephens, Dai; Strache, Nicole; Ströhle, Andreas; Struve, Maren; Subramaniam, Naresh; Theobald, David; Vetter, Nora; Vulser, Helene; Weiss, Katharina; Whelan, Robert; Williams, Steve; Xu, Bing; Yacubian, Juliana; Yu, Tao; Ziesch, Veronika

2017-01-01

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use. PMID:28221370

The Behavioral and Neural Mechanisms Underlying the Tracking of Expertise

PubMed Central

Boorman, Erie D.; O’Doherty, John P.; Adolphs, Ralph; Rangel, Antonio

2013-01-01

Summary Evaluating the abilities of others is fundamental for successful economic and social behavior. We investigated the computational and neurobiological basis of ability tracking by designing an fMRI task that required participants to use and update estimates of both people and algorithms’ expertise through observation of their predictions. Behaviorally, we find a model-based algorithm characterized subject predictions better than several alternative models. Notably, when the agent’s prediction was concordant rather than discordant with the subject’s own likely prediction, participants credited people more than algorithms for correct predictions and penalized them less for incorrect predictions. Neurally, many components of the mentalizing network—medial prefrontal cortex, anterior cingulate gyrus, temporoparietal junction, and precuneus—represented or updated expertise beliefs about both people and algorithms. Moreover, activity in lateral orbitofrontal and medial prefrontal cortex reflected behavioral differences in learning about people and algorithms. These findings provide basic insights into the neural basis of social learning. PMID:24360551

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

PubMed

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

2012-01-29

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

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

PubMed Central

Ruocco, Anthony C.; Rodrigo, Achala H.; McMain, Shelley F.; Page-Gould, Elizabeth; Ayaz, Hasan; Links, Paul S.

2016-01-01

Self-harm is a potentially lethal symptom of borderline personality disorder (BPD) that often improves with dialectical behavior therapy (DBT). While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, 29 actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex (PFC) during impulse control prior to beginning DBT and after 7 months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex (DLPFC) prior to beginning treatment, and they showed the greatest increases in activity within this region after 7 months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial PFC and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right DLPFC even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the PFC underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT. PMID:27242484

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

PubMed

Ruocco, Anthony C; Rodrigo, Achala H; McMain, Shelley F; Page-Gould, Elizabeth; Ayaz, Hasan; Links, Paul S

2016-01-01

Self-harm is a potentially lethal symptom of borderline personality disorder (BPD) that often improves with dialectical behavior therapy (DBT). While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, 29 actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex (PFC) during impulse control prior to beginning DBT and after 7 months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex (DLPFC) prior to beginning treatment, and they showed the greatest increases in activity within this region after 7 months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial PFC and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right DLPFC even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the PFC underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT.

The role of replay and theta sequences in mediating hippocampal-prefrontal interactions for memory and cognition.

PubMed

Zielinski, Mark C; Tang, Wenbo; Jadhav, Shantanu P

2017-12-18

Sequential activity is seen in the hippocampus during multiple network patterns, prominently as replay activity during both awake and sleep sharp-wave ripples (SWRs), and as theta sequences during active exploration. Although various mnemonic and cognitive functions have been ascribed to these hippocampal sequences, evidence for these proposed functions remains primarily phenomenological. Here, we briefly review current knowledge about replay events and theta sequences in spatial memory tasks. We reason that in order to gain a mechanistic and causal understanding of how these patterns influence memory and cognitive processing, it is important to consider how these sequences influence activity in other regions, and in particular, the prefrontal cortex, which is crucial for memory-guided behavior. For spatial memory tasks, we posit that hippocampal-prefrontal interactions mediated by replay and theta sequences play complementary and overlapping roles at different stages in learning, supporting memory encoding and retrieval, deliberative decision making, planning, and guiding future actions. This framework offers testable predictions for future physiology and closed-loop feedback inactivation experiments for specifically targeting hippocampal sequences as well as coordinated prefrontal activity in different network states, with the potential to reveal their causal roles in memory-guided behavior. © 2017 Wiley Periodicals, Inc.

Imitation and observational learning of hand actions: prefrontal involvement and connectivity.

PubMed

Higuchi, S; Holle, H; Roberts, N; Eickhoff, S B; Vogt, S

2012-01-16

The first aim of this event-related fMRI study was to identify the neural circuits involved in imitation learning. We used a rapid imitation task where participants directly imitated pictures of guitar chords. The results provide clear evidence for the involvement of dorsolateral prefrontal cortex, as well as the fronto-parietal mirror circuit (FPMC) during action imitation when the requirements for working memory are low. Connectivity analyses further indicated a robust connectivity between left prefrontal cortex and the components of the FPMC bilaterally. We conclude that a mechanism of automatic perception-action matching alone is insufficient to account for imitation learning. Rather, the motor representation of an observed, complex action, as provided by the FPMC, only serves as the 'raw material' for higher-order supervisory and monitoring operations associated with the prefrontal cortex. The second aim of this study was to assess whether these neural circuits are also recruited during observational practice (OP, without motor execution), or only during physical practice (PP). Whereas prefrontal cortex was not consistently activated in action observation across all participants, prefrontal activation intensities did predict the behavioural practice effects, thus indicating a crucial role of prefrontal cortex also in OP. In addition, whilst OP and PP produced similar activation intensities in the FPMC when assessed during action observation, during imitative execution, the practice-related activation decreases were significantly more pronounced for PP than for OP. This dissociation indicates a lack of execution-related resources in observationally practised actions. More specifically, we found neural efficiency effects in the right motor cingulate-basal ganglia circuit and the FPMC that were only observed after PP but not after OP. Finally, we confirmed that practice generally induced activation decreases in the FPMC during both action observation and imitation sessions and outline a framework explaining the discrepant findings in the literature. Copyright © 2011 Elsevier Inc. All rights reserved.

Homeostatic Regulation of Memory Systems and Adaptive Decisions

PubMed Central

Mizumori, Sheri JY; Jo, Yong Sang

2013-01-01

While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The “multiple memory systems of the brain” have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:23929788

Homeostatic regulation of memory systems and adaptive decisions.

PubMed

Mizumori, Sheri J Y; Jo, Yong Sang

2013-11-01

While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The "multiple memory systems of the brain" have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed

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

2015-03-04

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

Decoding the Formation of New Semantics: MVPA Investigation of Rapid Neocortical Plasticity during Associative Encoding through Fast Mapping.

PubMed

Atir-Sharon, Tali; Gilboa, Asaf; Hazan, Hananel; Koilis, Ester; Manevitz, Larry M

2015-01-01

Neocortical structures typically only support slow acquisition of declarative memory; however, learning through fast mapping may facilitate rapid learning-induced cortical plasticity and hippocampal-independent integration of novel associations into existing semantic networks. During fast mapping the meaning of new words and concepts is inferred, and durable novel associations are incidentally formed, a process thought to support early childhood's exuberant learning. The anterior temporal lobe, a cortical semantic memory hub, may critically support such learning. We investigated encoding of semantic associations through fast mapping using fMRI and multivoxel pattern analysis. Subsequent memory performance following fast mapping was more efficiently predicted using anterior temporal lobe than hippocampal voxels, while standard explicit encoding was best predicted by hippocampal activity. Searchlight algorithms revealed additional activity patterns that predicted successful fast mapping semantic learning located in lateral occipitotemporal and parietotemporal neocortex and ventrolateral prefrontal cortex. By contrast, successful explicit encoding could be classified by activity in medial and dorsolateral prefrontal and parahippocampal cortices. We propose that fast mapping promotes incidental rapid integration of new associations into existing neocortical semantic networks by activating related, nonoverlapping conceptual knowledge. In healthy adults, this is better captured by unique anterior and lateral temporal lobe activity patterns, while hippocampal involvement is less predictive of this kind of learning.

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

PubMed

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

2011-01-01

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

Functional neuroimaging of psychotherapeutic processes in anxiety and depression: from mechanisms to predictions.

PubMed

Lueken, Ulrike; Hahn, Tim

2016-01-01

The review provides an update of functional neuroimaging studies that identify neural processes underlying psychotherapy and predict outcomes following psychotherapeutic treatment in anxiety and depressive disorders. Following current developments in this field, studies were classified as 'mechanistic' or 'predictor' studies (i.e., informing neurobiological models about putative mechanisms versus aiming to provide predictive information). Mechanistic evidence points toward a dual-process model of psychotherapy in anxiety disorders with abnormally increased limbic activation being decreased, while prefrontal activity is increased. Partly overlapping findings are reported for depression, albeit with a stronger focus on prefrontal activation following treatment. No studies directly comparing neural pathways of psychotherapy between anxiety and depression were detected. Consensus is accumulating for an overarching role of the anterior cingulate cortex in modulating treatment response across disorders. When aiming to quantify clinical utility, the need for single-subject predictions is increasingly recognized and predictions based on machine learning approaches show high translational potential. Present findings encourage the search for predictors providing clinically meaningful information for single patients. However, independent validation as a crucial prerequisite for clinical use is still needed. Identifying nonresponders a priori creates the need for alternative treatment options that can be developed based on an improved understanding of those neural mechanisms underlying effective interventions.

Longitudinal development of prefrontal function during early childhood.

PubMed

Moriguchi, Yusuke; Hiraki, Kazuo

2011-04-01

This is a longitudinal study on development of prefrontal function in young children. Prefrontal areas have been observed to develop dramatically during early childhood. To elucidate this development, we gave children cognitive shifting tasks related to prefrontal function at 3 years of age (Time 1) and 4 years of age (Time 2). We then monitored developmental changes in behavioral performance and examined prefrontal activation using near infrared spectroscopy. We found that children showed better behavioral performance and significantly stronger inferior prefrontal activation at Time 2 than they did at Time 1. Moreover, we demonstrated individual differences in prefrontal activation for the same behavioral tasks. Children who performed better in tasks at Time 1 showed significant activation of the right inferior prefrontal regions at Time 1 and significant activation of the bilateral inferior prefrontal regions at Time 2. Children who showed poorer performance at Time 1 exhibited no significant inferior prefrontal activation at Time 1 but significant left inferior prefrontal activation at Time 2. These results indicate the importance of the longitudinal method to address the link between cognitive and neural development. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-08-30

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

A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity

PubMed Central

Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

2016-01-01

The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition. PMID:27203563

Recognition memory of newly learned faces.

PubMed

Ishai, Alumit; Yago, Elena

2006-12-11

We used event-related fMRI to study recognition memory of newly learned faces. Caucasian subjects memorized unfamiliar, neutral and happy South Korean faces and 4 days later performed a memory retrieval task in the MR scanner. We predicted that previously seen faces would be recognized faster and more accurately and would elicit stronger neural activation than novel faces. Consistent with our hypothesis, novel faces were recognized more slowly and less accurately than previously seen faces. We found activation in a distributed cortical network that included face-responsive regions in the visual cortex, parietal and prefrontal regions, and the hippocampus. Within all regions, correctly recognized, previously seen faces evoked stronger activation than novel faces. Additionally, in parietal and prefrontal cortices, stronger activation was observed during correct than incorrect trials. Finally, in the hippocampus, false alarms to happy faces elicited stronger responses than false alarms to neutral faces. Our findings suggest that face recognition memory is mediated by stimulus-specific representations stored in extrastriate regions; parietal and prefrontal regions where old and new items are classified; and the hippocampus where veridical memory traces are recovered.

Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding

PubMed Central

Guise, Kevin G.; Shapiro, Matthew L.

2017-01-01

Summary 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. PMID:28343868

Response to learned threat: An FMRI study in adolescent and adult anxiety.

PubMed

Britton, Jennifer C; Grillon, Christian; Lissek, Shmuel; Norcross, Maxine A; Szuhany, Kristin L; Chen, Gang; Ernst, Monique; Nelson, Eric E; Leibenluft, Ellen; Shechner, Tomer; Pine, Daniel S

2013-10-01

Poor threat-safety discrimination reflects prefrontal cortex dysfunction in adult anxiety disorders. While adolescent anxiety disorders are impairing and predict high risk for adult anxiety disorders, the neural correlates of threat-safety discrimination have not been investigated in this population. The authors compared prefrontal cortex function in anxious and healthy adolescents and adults following conditioning and extinction, processes requiring threat-safety learning. Anxious and healthy adolescents and adults (N=114) completed fear conditioning and extinction in the clinic. The conditioned stimuli (CS+) were neutral faces, paired with an aversive scream. Physiological and subjective data were acquired. Three weeks later, 82 participants viewed the CS+ and morphed images resembling the CS+ in an MRI scanner. During scanning, participants made difficult threat-safety discriminations while appraising threat and explicit memory of the CS+. During conditioning and extinction, the anxious groups reported more fear than the healthy groups, but the anxious adolescent and adult groups did not differ on physiological measures. During imaging, both anxious adolescents and adults exhibited lower activation in the subgenual anterior cingulate cortex than their healthy counterparts, specifically when appraising threat. Compared with their age-matched counterpart groups, anxious adults exhibited reduced activation in the ventromedial prefrontal cortex when appraising threat, whereas anxious adolescents exhibited a U-shaped pattern of activation, with greater activation in response to the most extreme CS+ and CS-. Two regions of the prefrontal cortex are involved in anxiety disorders. Reduced subgenual anterior cingulate cortex engagement is a shared feature in adult and adolescent anxiety disorders, but ventromedial prefrontal cortex dysfunction is age-specific. The unique U-shaped pattern of activation in the ventromedial prefrontal cortex in many anxious adolescents may reflect heightened sensitivity to threat and safety conditions. How variations in the pattern relate to later risk for adult illness remains to be determined.

The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

PubMed

Silton, Rebecca Levin; Heller, Wendy; Towers, David N; Engels, Anna S; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2010-04-15

A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model. Copyright 2009 Elsevier Inc. All rights reserved.

Response of dorsomedial prefrontal cortex predicts altruistic behavior

PubMed Central

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

2012-01-01

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

Predicting Clinical Outcome Using Brain Activation Associated with Set-Shifting and Central Coherence Skills in Anorexia Nervosa

PubMed Central

Garrett, Amy; Lock, James; Datta, Nandini; Beenhaker, Judy; Kesler, Shelli R.; Reiss, Allan L.

2014-01-01

Background Patients with Anorexia Nervosa (AN) have neuropsychological deficits in set shifting (SS) and central coherence (CC) consistent with an inflexible thinking style and overly detailed processing style, respectively. This study investigates brain activation during SS and CC tasks in patients with AN and tests whether this activation is a biomarker that predicts response to treatment. Methods : FMRI data were collected from 21 females with AN while performing a SS task (the Wisconsin Card Sort) and a CC task (embedded figures), and used to predict outcome following 16 weeks of treatment (either 16 weeks of cognitive behavioral therapy or 8 weeks cognitive remediation training followed by 8 weeks of cognitive behavioral therapy). Results Significant activation during the SS task included bilateral dorsolateral and ventrolateral prefrontal cortex and left anterior middle frontal gyrus. Higher scores on the neuropsychological test of SS (measured outside the scanner at baseline) were correlated with greater DLPFC and VLPFC activation. Improvements in SS following treatment were significantly predicted by a combination of low VLPFC and high anterior middle frontal activation (R squared = .68, p=.001). For the CC task, the visual and parietal areas were activated, but were not significantly correlated with neuropsychological measures of CC and did not predict outcome. Conclusion Cognitive flexibility requires the support of several prefrontal cortex resources. As previous studies suggest that the VLPFC is important for selecting responses, patients who demonstrate that deficit may benefit the most from cognitive therapy with or without cognitive remediation training. The ability to sustain inhibition of an unwanted response, subserved by the anterior middle frontal gyrus, is a cognitive feature that predicts favorable outcome to cognitive treatment. CC deficits may not be an effective predictor of clinical outcome. PMID:25027478

The Neural Basis of Event Simulation: An fMRI Study

PubMed Central

Yomogida, Yukihito; Sugiura, Motoaki; Akimoto, Yoritaka; Miyauchi, Carlos Makoto; Kawashima, Ryuta

2014-01-01

Event simulation (ES) is the situational inference process in which perceived event features such as objects, agents, and actions are associated in the brain to represent the whole situation. ES provides a common basis for various cognitive processes, such as perceptual prediction, situational understanding/prediction, and social cognition (such as mentalizing/trait inference). Here, functional magnetic resonance imaging was used to elucidate the neural substrates underlying important subdivisions within ES. First, the study investigated whether ES depends on different neural substrates when it is conducted explicitly and implicitly. Second, the existence of neural substrates specific to the future-prediction component of ES was assessed. Subjects were shown contextually related object pictures implying a situation and performed several picture–word-matching tasks. By varying task goals, subjects were made to infer the implied situation implicitly/explicitly or predict the future consequence of that situation. The results indicate that, whereas implicit ES activated the lateral prefrontal cortex and medial/lateral parietal cortex, explicit ES activated the medial prefrontal cortex, posterior cingulate cortex, and medial/lateral temporal cortex. Additionally, the left temporoparietal junction plays an important role in the future-prediction component of ES. These findings enrich our understanding of the neural substrates of the implicit/explicit/predictive aspects of ES-related cognitive processes. PMID:24789353

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

PubMed

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

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

The Predictive Brain State: Asynchrony in Disorders of Attention?

PubMed Central

Ghajar, Jamshid; Ivry, Richard B.

2015-01-01

It is postulated that a key function of attention in goal-oriented behavior is to reduce performance variability by generating anticipatory neural activity that can be synchronized with expected sensory information. A network encompassing the prefrontal cortex, parietal lobe, and cerebellum may be critical in the maintenance and timing of such predictive neural activity. Dysfunction of this temporal process may constitute a fundamental defect in attention, causing working memory problems, distractibility, and decreased awareness. PMID:19074688

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

PubMed

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-07-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function

PubMed Central

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L.; Rajah, M. Natasha

2016-01-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. PMID:25882039

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

PubMed Central

Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

2016-01-01

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

Greater Working Memory Load Results in Greater Medial Temporal Activity at Retrieval

PubMed Central

Quiroz, Yakeel T.; Hasselmo, Michael E.; Stern, Chantal E.

2009-01-01

Most functional magnetic resonance imaging (fMRI) studies examining working memory (WM) load have focused on the prefrontal cortex (PFC) and have demonstrated increased prefrontal activity with increased load. Here we examined WM load effects in the medial temporal lobe (MTL) using an fMRI Sternberg task with novel complex visual scenes. Trials consisted of 3 sequential events: 1) sample presentation (encoding), 2) delay period (maintenance), and 3) probe period (retrieval). During sample encoding, subjects saw either 2 or 4 pictures consecutively. During retrieval, subjects indicated whether the probe picture matched one of the sample pictures. Results revealed that activity in the left anterior hippocampal formation, bilateral retrosplenial area, and left amygdala was greater at retrieval for trials with larger memory load, whereas activity in the PFC was greater at encoding for trials with larger memory load. There was no load effect during the delay. When encoding, maintenance, and retrieval periods were compared with fixation, activity was present in the hippocampal body/tail and fusiform gyrus bilaterally during encoding and retrieval, but not maintenance. Bilateral dorsolateral prefrontal activity was present during maintenance, but not during encoding or retrieval. The results support models of WM predicting that activity in the MTL should be modulated by WM load. PMID:19224975

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study.

PubMed

Cano, Marta; Cardoner, Narcís; Urretavizcaya, Mikel; Martínez-Zalacaín, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodríguez, Oren; Camprodon, Joan; de Arriba-Arnau, Aida; Hernández-Ribas, Rosa; Pujol, Jesús; Soriano-Mas, Carles; Menchón, José M

2016-01-01

Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

Boonstra, Tjeerd W.; Loo, Colleen K.; Martin, Donel

2017-01-01

Prefrontal cortex activity has been associated with changes to heart rate variability (HRV) via mediation of the cortico-subcortical pathways that regulate the parasympathetic and sympathetic branches of the autonomic nervous system. Changes in HRV due to altered prefrontal cortex functioning can be predicted using the neurovisceral integration model, which suggests that prefrontal hyperactivity increases parasympathetic tone and decreases contributions from the sympathetic nervous system. Working memory (WM) tasks and transcranial direct current stimulation (tDCS) have been used independently to modulate brain activity demonstrating changes to HRV in agreement with the model. We investigated the combined effects of prefrontal tDCS and a WM task on HRV. Bifrontal tDCS was administered for 15 minutes at 2mA to 20 participants in a sham controlled, single-blind study using parallel groups. A WM task was completed by participants at three time points; pre-, during-, and post-tDCS, with resting state data collected at similar times. Frequency-domain HRV was computed for high frequency (HF; 0.15–0.4Hz) and low frequency (LF; 0.04–0.15Hz) power reflecting parasympathetic and sympathetic branch activity, respectively. Response time on the WM task, but not accuracy, improved from baseline to during-tDCS and post-tDCS with sham, but not active, stimulation. HF-HRV was significantly increased in the active tDCS group compared to sham, lasting beyond cessation of stimulation. Additionally, HF-HRV showed a task-related reduction in power during performance on the WM task. Changes in LF-HRV were moderately inversely correlated (r > 0.4) with changes in WM accuracy during and following tDCS compared to baseline levels. Stimulation of the prefrontal cortex resulted in changes to the parasympathetic branch of the nervous system in agreement with a linearly additive interpretation of effects. Sympathetic activity was not directly altered by tDCS, but was correlated with changes in WM performance. This suggests that the parasympathetic and sympathetic branches respond differentially due to similar, but distinct neural pathways. Given the ease of HRV data collection, studies of prefrontal tDCS would benefit from collection of this data as it provides unique insight into tDCS effects resulting from propagation through brain networks. PMID:28771509

Brain signatures of moral sensitivity in adolescents with early social deprivation.

PubMed

Escobar, María Josefina; Huepe, David; Decety, Jean; Sedeño, Lucas; Messow, Marie Kristin; Baez, Sandra; Rivera-Rei, Álvaro; Canales-Johnson, Andrés; Morales, Juan Pablo; Gómez, David Maximiliano; Schröeder, Johannes; Manes, Facundo; López, Vladimir; Ibánez, Agustín

2014-06-19

The present study examined neural responses associated with moral sensitivity in adolescents with a background of early social deprivation. Using high-density electroencephalography (hdEEG), brain activity was measured during an intentional inference task, which assesses rapid moral decision-making regarding intentional or unintentional harm to people and objects. We compared the responses to this task in a socially deprived group (DG) with that of a control group (CG). The event-related potentials (ERPs) results showed atypical early and late frontal cortical markers associated with attribution of intentionality during moral decision-making in DG (especially regarding intentional harm to people). The source space of the hdEEG showed reduced activity for DG compared with CG in the right prefrontal cortex, bilaterally in the ventromedial prefrontal cortex (vmPFC), and right insula. Moreover, the reduced response in vmPFC for DG was predicted by higher rates of externalizing problems. These findings demonstrate the importance of the social environment in early moral development, supporting a prefrontal maturation model of social deprivation.

Concepts in context: Processing mental state concepts with internal or external focus involves different neural systems

PubMed Central

Oosterwijk, Suzanne; Mackey, Scott; Wilson-Mendenhall, Christine; Winkielman, Piotr; Paulus, Martin P.

2015-01-01

According to embodied cognition theories concepts are contextually-situated and grounded in neural systems that produce experiential states. This view predicts that processing mental state concepts recruits neural regions associated with different aspects of experience depending on the context in which people understand a concept. This neuroimaging study tested this prediction using a set of sentences that described emotional (e.g., fear, joy) and non-emotional (e.g., thinking, hunger) mental states with internal focus (i.e. focusing on bodily sensations and introspection) or external focus (i.e. focusing on expression and action). Consistent with our predictions, data suggested that the inferior frontal gyrus, a region associated with action representation, was engaged more by external than internal sentences. By contrast, the ventromedial prefrontal cortex, a region associated with the generation of internal states, was engaged more by internal emotion sentences than external sentence categories. Similar patterns emerged when we examined the relationship between neural activity and independent ratings of sentence focus. Furthermore, ratings of emotion were associated with activation in the medial prefrontal cortex, whereas ratings of activity were associated with activation in the inferior frontal gyrus. These results suggest that mental state concepts are represented in a dynamic way, using context-relevant interoceptive and sensorimotor resources. PMID:25748274

Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

PubMed Central

Tully, Laura M.; Lincoln, Sarah Hope; Hooker, Christine I.

2014-01-01

LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia. PMID:25379415

Preparatory neural activity predicts performance on a conflict task.

PubMed

Stern, Emily R; Wager, Tor D; Egner, Tobias; Hirsch, Joy; Mangels, Jennifer A

2007-10-24

Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.

Global connectivity of prefrontal cortex predicts cognitive control and intelligence

PubMed Central

Cole, Michael W.; Yarkoni, Tal; Repovs, Grega; Anticevic, Alan; Braver, Todd S.

2012-01-01

Control of thought and behavior is fundamental to human intelligence. Evidence suggests a fronto-parietal brain network implements such cognitive control across diverse contexts. We identify a mechanism – global connectivity – by which components of this network might coordinate control of other networks. A lateral prefrontal cortex (LPFC) region’s activity was found to predict performance in a high control demand working memory task, and also to exhibit high global connectivity. Critically, global connectivity in this LPFC region, involving connections both within and outside the fronto-parietal network, showed a highly selective relationship with individual differences in fluid intelligence. These findings suggest LPFC is a global hub with a brain-wide influence that facilitates the ability to implement control processes central to human intelligence. PMID:22745498

The relationship of resting cerebral blood flow and brain activation during a social cognition task in adolescents with chronic moderate to severe traumatic brain injury: a preliminary investigation.

PubMed

Newsome, Mary R; Scheibel, Randall S; Chu, Zili; Hunter, Jill V; Li, Xiaoqi; Wilde, Elisabeth A; Lu, Hanzhang; Wang, Zhiyue J; Lin, Xiaodi; Steinberg, Joel L; Vasquez, Ana C; Cook, Lori; Levin, Harvey S

2012-05-01

Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI. Published by Elsevier Ltd.

Prefrontal over-activation during walking in people with mobility deficits: Interpretation and functional implications.

PubMed

Hawkins, Kelly A; Fox, Emily J; Daly, Janis J; Rose, Dorian K; Christou, Evangelos A; McGuirk, Theresa E; Otzel, Dana M; Butera, Katie A; Chatterjee, Sudeshna A; Clark, David J

2018-06-01

Control of walking by the central nervous system includes contributions from executive control mechanisms, such as attention and motor planning resources. Executive control of walking can be estimated objectively by recording prefrontal cortical activity using functional near infrared spectroscopy (fNIRS). The primary objective of this study was to investigate group differences in prefrontal/executive control of walking among young adults, older adults, and adults post-stroke. Also assessed was the extent to which walking-related prefrontal activity fits existing cognitive frameworks of prefrontal over-activation. Participants included 24 adults post-stroke with moderate to severe walking deficits, 15 older adults with mild gait deficits, and 9 young healthy adults. Executive control of walking was quantified as oxygenated hemoglobin concentration in the prefrontal cortex measured by fNIRS. Three walking tasks were assessed: typical walking, walking over obstacles, and walking while performing a verbal fluency task. Walking performance was assessed by walking speed. There was a significant effect of group for prefrontal activity (p < 0.001) during typical and obstacles walking tasks, with young adults exhibiting the lowest level of prefrontal activity, followed by older adults, and then adults post-stroke. In young adults the prefrontal activity during typical walking was much lower than for the verbal fluency dual-task, suggesting substantial remaining prefrontal resources during typical walking. However, in older and post-stroke adults these remaining resources were significantly less (p < 0.01). Cumulatively, these results are consistent with prefrontal over-activation in the older and stroke groups, which was accompanied by a steeper drop in walking speed as task complexity increased to include obstacles (p < 0.05). There is a heightened use of prefrontal/executive control resources in older adults and post-stroke adults during walking. The level of prefrontal resource utilization, particularly during complex walking tasks like obstacle crossing, may approach the ceiling of available resources for people who have walking deficits. Prior cognitive research has revealed that prefrontal over-activation combined with limited prefrontal resources can lead to poor cognitive performance. The present study suggests a similar situation influences walking performance. Future research should further investigate the extent to which prefrontal over-activation during walking is linked to adverse mobility outcomes. Published by Elsevier B.V.

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

PubMed

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

2016-01-01

Perhaps the most widely studied effect to emerge from the combination of neuroimaging and human genetics is the association of the COMT-Val(108/158)Met polymorphism with prefrontal activity during working memory. COMT-Val is a putative risk factor in schizophrenia, which is characterized by disordered prefrontal function. Work in healthy populations has sought to characterize mechanisms by which the valine (Val) allele may lead to disadvantaged prefrontal cognition. Lower activity in methionine (Met) carriers has been interpreted as advantageous neural efficiency. Notably, however, studies reporting COMT effects on neural efficiency have generally not reported working memory performance effects. Those studies have employed relatively low/easy working memory loads. Higher loads are known to elicit individual differences in working memory performance that are not visible at lower loads. If COMT-Met confers greater neural efficiency when working memory is easy, a reasonable prediction is that Met carriers will be better able to cope with increasing demand for neural resources when working memory becomes difficult. To our knowledge, this prediction has thus far gone untested. Here, we tested performance on three working memory tasks. Performance on each task was measured at multiple levels of load/difficulty, including loads more demanding than those used in prior studies. We found no genotype-by-load interactions or main effects of COMT genotype on accuracy or reaction time. Indeed, even testing for performance differences at each load of each task failed to find a single significant effect of COMT genotype. Thus, even if COMT genotype has the effects on prefrontal efficiency that prior work has suggested, such effects may not directly impact high-load working memory ability. The present findings accord with previous evidence that behavioral effects of COMT are small or nonexistent and, more broadly, with a growing consensus that substantial effects on phenotype will not emerge from candidate gene studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

In search of integrative processes: basic psychological need satisfaction predicts medial prefrontal activation during decisional conflict.

PubMed

Di Domenico, Stefano I; Fournier, Marc A; Ayaz, Hasan; Ruocco, Anthony C

2013-08-01

Research has shown that people's abilities to develop and act from a coherent sense of self are facilitated by satisfaction of the basic psychological needs for competence, relatedness, and autonomy. The present study utilized functional near infrared spectroscopy (fNIRS) to examine the effect of need satisfaction on activity in the medial prefrontal cortex (MPFC), a key region in processing information about the self. Participants completed a decision-making task (e.g., Which occupation would you prefer, dancer or chemist?) in which they made a series of forced choices according to their personal preferences. The degree of decisional conflict (i.e., choice difficulty) between the available response options was manipulated on the basis of participants' unique preference ratings for the target stimuli, which were obtained prior to scanning. Need satisfaction predicted elevated MPFC activity during high-conflict relative to low-conflict situations, suggesting that one way need satisfaction may promote self-coherence is by enhancing the utilization of self-knowledge in the resolution of decisional conflicts. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity.

PubMed

Berkers, Ruud M W J; Klumpers, Floris; Fernández, Guillén

2016-10-01

Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories. Copyright © 2016 Elsevier Inc. All rights reserved.

Differences in reward processing between putative cell types in primate prefrontal cortex

PubMed Central

Fan, Hongwei; Wang, Rubin; Sakagami, Masamichi

2017-01-01

Single-unit studies in monkeys have demonstrated that neurons in the prefrontal cortex predict the reward type, reward amount or reward availability associated with a stimulus. To examine contributions of pyramidal cells and interneurons in reward processing, single-unit activity was extracellularly recorded in prefrontal cortices of four monkeys performing a reward prediction task. Based on their shapes of spike waveforms, prefrontal neurons were classified into broad-spike and narrow-spike units that represented putative pyramidal cells and interneurons, respectively. We mainly observed that narrow-spike neurons showed higher firing rates but less bursty discharges than did broad-spike neurons. Both narrow-spike and broad-spike cells selectively responded to the stimulus, reward and their interaction, and the proportions of each type of selective neurons were similar between the two cell classes. Moreover, the two types of cells displayed equal reliability of reward or stimulus discrimination. Furthermore, we found that broad-spike and narrow-spike cells showed distinct mechanisms for encoding reward or stimulus information. Broad-spike neurons raised their firing rate relative to the baseline rate to represent the preferred reward or stimulus information, whereas narrow-spike neurons inhibited their firing rate lower than the baseline rate to encode the non-preferred reward or stimulus information. Our results suggest that narrow-spike and broad-spike cells were equally involved in reward and stimulus processing in the prefrontal cortex. They utilized a binary strategy to complementarily represent reward or stimulus information, which was consistent with the task structure in which the monkeys were required to remember two reward conditions and two visual stimuli. PMID:29261734

Differences in reward processing between putative cell types in primate prefrontal cortex.

PubMed

Fan, Hongwei; Pan, Xiaochuan; Wang, Rubin; Sakagami, Masamichi

2017-01-01

Single-unit studies in monkeys have demonstrated that neurons in the prefrontal cortex predict the reward type, reward amount or reward availability associated with a stimulus. To examine contributions of pyramidal cells and interneurons in reward processing, single-unit activity was extracellularly recorded in prefrontal cortices of four monkeys performing a reward prediction task. Based on their shapes of spike waveforms, prefrontal neurons were classified into broad-spike and narrow-spike units that represented putative pyramidal cells and interneurons, respectively. We mainly observed that narrow-spike neurons showed higher firing rates but less bursty discharges than did broad-spike neurons. Both narrow-spike and broad-spike cells selectively responded to the stimulus, reward and their interaction, and the proportions of each type of selective neurons were similar between the two cell classes. Moreover, the two types of cells displayed equal reliability of reward or stimulus discrimination. Furthermore, we found that broad-spike and narrow-spike cells showed distinct mechanisms for encoding reward or stimulus information. Broad-spike neurons raised their firing rate relative to the baseline rate to represent the preferred reward or stimulus information, whereas narrow-spike neurons inhibited their firing rate lower than the baseline rate to encode the non-preferred reward or stimulus information. Our results suggest that narrow-spike and broad-spike cells were equally involved in reward and stimulus processing in the prefrontal cortex. They utilized a binary strategy to complementarily represent reward or stimulus information, which was consistent with the task structure in which the monkeys were required to remember two reward conditions and two visual stimuli.

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.

Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder.

PubMed

Chang, Kiki; Garrett, Amy; Kelley, Ryan; Howe, Meghan; Sanders, Erica Marie; Acquaye, Tenah; Bararpour, Layla; Li, Sherrie; Singh, Manpreet; Jo, Booil; Hallmayer, Joachim; Reiss, Allan

2017-11-01

Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD. We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene. While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex CONCLUSIONS: Similar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD. Copyright © 2017. Published by Elsevier B.V.

Saccade-related activity in the prefrontal cortex: its role in eye movement control and cognitive functions

PubMed Central

Funahashi, Shintaro

2014-01-01

Prefrontal neurons exhibit saccade-related activity and pre-saccadic memory-related activity often encodes the directions of forthcoming eye movements, in line with demonstrated prefrontal contribution to flexible control of voluntary eye movements. However, many prefrontal neurons exhibit post-saccadic activity that is initiated well after the initiation of eye movement. Although post-saccadic activity has been observed in the frontal eye field, this activity is thought to be a corollary discharge from oculomotor centers, because this activity shows no directional tuning and is observed whenever the monkeys perform eye movements regardless of goal-directed or not. However, prefrontal post-saccadic activities exhibit directional tunings similar as pre-saccadic activities and show context dependency, such that post-saccadic activity is observed only when monkeys perform goal-directed saccades. Context-dependency of prefrontal post-saccadic activity suggests that this activity is not a result of corollary signals from oculomotor centers, but contributes to other functions of the prefrontal cortex. One function might be the termination of memory-related activity after a behavioral response is done. This is supported by the observation that the termination of memory-related activity coincides with the initiation of post-saccadic activity in population analyses of prefrontal activities. The termination of memory-related activity at the end of the trial ensures that the subjects can prepare to receive new and updated information. Another function might be the monitoring of behavioral performance, since the termination of memory-related activity by post-saccadic activity could be associated with informing the correctness of the response and the termination of the trial. However, further studies are needed to examine the characteristics of saccade-related activities in the prefrontal cortex and their functions in eye movement control and a variety of cognitive functions. PMID:25071482

Theta synchronizes the activity of medial prefrontal neurons during learning

PubMed Central

Paz, Rony; Bauer, Elizabeth P.; Paré, Denis

2008-01-01

Memory consolidation is thought to involve the gradual transfer of transient hippocampal-dependent traces to distributed neocortical sites via the rhinal cortices. Recently, medial prefrontal (mPFC) neurons were shown to facilitate this process when their activity becomes synchronized. However, the mechanisms underlying this enhanced synchrony remain unclear. Because the hippocampus projects to the mPFC, we tested whether theta oscillations contribute to synchronize mPFC neurons during learning. Thus, we obtained field (LFP) and unit recordings from multiple mPFC sites during the acquisition of a trace-conditioning task, where a visual conditioned stimulus (CS) predicted reward delivery. In quiet waking, the activity of mPFC neurons was modulated by theta oscillations. During conditioning, CS presentation caused an increase in mPFC theta power that augmented as the CS gained predictive value for reward delivery. This increased theta power coincided with a transient theta phase locking at distributed mPFC sites, an effect that was also manifest in the timing of mPFC unit activity. Overall, these results show that theta oscillations contribute to synchronize neuronal activity at distributed mPFC sites, suggesting that the hippocampus, by generating a stronger theta source during learning, can synchronize mPFC activity, in turn facilitating rhinal transfer of its activity to the neocortex. PMID:18612069

Can neural activation in dorsolateral prefrontal cortex predict responsiveness to information? An application to egg production systems and campaign advertising.

PubMed

McFadden, Brandon R; Lusk, Jayson L; Crespi, John M; Cherry, J Bradley C; Martin, Laura E; Aupperle, Robin L; Bruce, Amanda S

2015-01-01

Consumers prefer to pay low prices and increase animal welfare; however consumers are typically forced to make tradeoffs between price and animal welfare. Campaign advertising (i.e., advertising used during the 2008 vote on Proposition 2 in California) may affect how consumers make tradeoffs between price and animal welfare. Neuroimaging data was used to determine the effects of brain activation in dorsolateral prefrontal cortex (dlPFC) on choices making a tradeoff between price and animal welfare and responsiveness to campaign advertising. Results indicated that activation in the dlPFC was greater when making choices that forced a tradeoff between price and animal welfare, compared to choices that varied only by price or animal welfare. Furthermore, greater activation differences in right dlPFC between choices that forced a tradeoff and choices that did not, indicated greater responsiveness to campaign advertising.

Can Neural Activation in Dorsolateral Prefrontal Cortex Predict Responsiveness to Information? An Application to Egg Production Systems and Campaign Advertising

PubMed Central

McFadden, Brandon R.; Lusk, Jayson L.; Crespi, John M.; Cherry, J. Bradley C.; Martin, Laura E.; Aupperle, Robin L.; Bruce, Amanda S.

2015-01-01

Consumers prefer to pay low prices and increase animal welfare; however consumers are typically forced to make tradeoffs between price and animal welfare. Campaign advertising (i.e., advertising used during the 2008 vote on Proposition 2 in California) may affect how consumers make tradeoffs between price and animal welfare. Neuroimaging data was used to determine the effects of brain activation in dorsolateral prefrontal cortex (dlPFC) on choices making a tradeoff between price and animal welfare and responsiveness to campaign advertising. Results indicated that activation in the dlPFC was greater when making choices that forced a tradeoff between price and animal welfare, compared to choices that varied only by price or animal welfare. Furthermore, greater activation differences in right dlPFC between choices that forced a tradeoff and choices that did not, indicated greater responsiveness to campaign advertising. PMID:26018592

Deficits in process-specific prefrontal and hippocampal activations contribute to adult age differences in episodic memory interference.

PubMed

Fandakova, Yana; Lindenberger, Ulman; Shing, Yee Lee

2014-07-01

The ability to distinguish currently relevant from familiar but irrelevant memories is important in everyday life. We used functional magnetic resonance imaging to examine the neural correlates of age differences in the ability to withstand interference from similar past events. Younger and older adults worked on a continuous recognition task consisting of 3 consecutive runs. Each run was composed of the same set of word pairs, and participants were instructed to recognize word pair repetitions within runs. The monitoring demands associated with rejecting familiar, but currently irrelevant information were assumed to increase over consecutive runs. Over runs, older, but not younger adults showed decline in memory performance, whereas younger, but not older adults showed increasing engagement of anterior prefrontal cortex. Individual differences in cortical thickness and task-related activation of anterior prefrontal areas predicted performance differences within and across age groups. Compared with younger adults, older adults also showed a reduced hippocampal response to novel associations of familiar stimuli. We conclude that monitoring deficits due to impaired involvement of prefrontal regions and reduced hippocampal responses to associative novelty contribute to aging-related deficits in disambiguating the contextual information of familiar events. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neural networks involved in artistic creativity.

PubMed

Kowatari, Yasuyuki; Lee, Seung Hee; Yamamura, Hiromi; Nagamori, Yusuke; Levy, Pierre; Yamane, Shigeru; Yamamoto, Miyuki

2009-05-01

Creativity has been proposed to be either the result of solely right hemisphere processes or of interhemispheric interactions. Little information is available, however, concerning the neuronal foundations of creativity. In this study, we introduced a new artistic task, designing a new tool (a pen), which let us quantitatively evaluate creativity by three indices of originality. These scores were analyzed in combination with brain activities measured by functional magnetic resonance imaging (fMRI). The results were compared between subjects who had been formally trained in design (experts) and novice subjects. In the experts, creativity was quantitatively correlated with the degree of dominance of the right prefrontal cortex over that of the left, but not with that of the right or left prefrontal cortex alone. In contrast, in novice subjects, only a negative correlation with creativity was observed in the bilateral inferior parietal cortex. We introduced structure equation modeling to analyze the interactions among these four brain areas and originality indices. The results predicted that training exerts a direct effect on the left parietal cortex. Additionally, as a result of the indirect effects, the activity of the right prefrontal cortex was facilitated, and the left prefrontal and right parietal cortices were suppressed. Our results supported the hypothesis that training increases creativity via reorganized intercortical interactions. (c) 2008 Wiley-Liss, Inc.

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis.

PubMed

Yamamoto, Dorothy J; Woo, Choong-Wan; Wager, Tor D; Regner, Michael F; Tanabe, Jody

2015-04-01

Alterations in frontal and striatal function are hypothesized to underlie risky decision making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. RDLPFC activity mediated less risky decision making while VST mediated more risky decision making across drug users and controls. These results suggest a dual pathway underlying decision making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis*

PubMed Central

Yamamoto, Dorothy J.; Woo, Choong-Wan; Wager, Tor D.; Regner, Michael F.; Tanabe, Jody

2015-01-01

Background Alterations in frontal and striatal function are hypothesized to underlie risky decision-making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Method Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Results Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. controls. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. Conclusion RDLPFC activity mediated less risky decision-making while VST mediated more risky decision-making across drug users and controls. These results suggest a dual pathway underlying decision-making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. PMID:25736619

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

Enhanced pain expectation in migraine: EEG-based evidence for impaired prefrontal function.

PubMed

Lev, Rina; Granovsky, Yelena; Yarnitsky, David

2013-01-01

Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9 μV) and unchanged ones in MOAs (1.1 μV) but not in controls (decrease of 5 μV). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5 μV and 4.4 μV, respectively) compared with controls (decrease of 0.2 μV). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P < .05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P < .05) and concern of upcoming migraine attacks (P < .05) in MWAs, and with frequency of migraine attacks in MOAs (P < .05). Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks. © 2012 American Headache Society.

Neural Correlates of Graphic Cigarette Warning Labels Predict Smoking Cessation Relapse

PubMed Central

Owens, Max M.; MacKillop, James; Gray, Joshua C.; Hawkshead, Brittany E.; Murphy, Cara M.; Sweet, Lawrence H.

2017-01-01

Exposure to graphic warning labels (GWLs) on cigarette packaging has been found to produce heightened activity in brain regions central to emotional processing and higher-order cognitive processes. The current study extends this literature by using functional magnetic resonance imaging (fMRI) to investigate neural activation in response to GWLs and use it to predict relapse in an evidence-based smoking cessation treatment program. Participants were 48 treatment-seeking nicotine-dependent smokers who completed an fMRI paradigm in which they were exposed to GWLs, text-only warning labels (TOLs), and matched control stimuli. Subsequently, they enrolled in smoking cessation treatment and their smoking behavior was monitored. Activation in bilateral amygdala, right dorsolateral prefrontal cortex, right inferior frontal gyrus, left medial temporal gyrus, bilateral occipital lobe, and bilateral fusiform gyrus was greater during GWLs than TOLs. Neural response in the ventromedial prefrontal cortex (vmPFC) during exposure to GWLs (relative to a visual control image) predicted relapse during treatment beyond baseline demographic and dependence severity, but response in the amygdala to GWLs did not. These findings suggest that neurocognitive processes in the vmPFC may be critical to understanding how GWL’s induce behavior change and may be useful as a predictor of smoking cessation treatment prognosis. PMID:28236714

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

PubMed

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L; Rajah, M Natasha

2016-06-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Preschool Anxiety Disorders Predict Different Patterns of Amygdala-Prefrontal Connectivity at School-Age

PubMed Central

Carpenter, Kimberly L. H.; Angold, Adrian; Chen, Nan-Kuei; Copeland, William E.; Gaur, Pooja; Pelphrey, Kevin; Song, Allen W.; Egger, Helen L.

2015-01-01

Objective In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. Methods Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. Results A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. Conclusions Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders. PMID:25625285

Association between severe dorsolateral prefrontal dysfunction during random number generation and earlier onset in schizophrenia.

PubMed

Koike, Shinsuke; Takizawa, Ryu; Nishimura, Yukika; Marumo, Kohei; Kinou, Masaru; Kawakubo, Yuki; Rogers, Mark A; Kasai, Kiyoto

2011-08-01

Schizophrenia involves impairment in attention, working memory and executive processes associated with prefrontal cortical function, an essential contributor of social functioning. Age at onset is a major factor for predicting social outcome in schizophrenia. In clinical settings, we need an objective assessment tool for evaluating prefrontal function and social outcome. Participants included 22 right-handed patients with schizophrenia and 40 gender- and age-matched healthy controls. We used a 52-channel near-infrared spectroscopy (NIRS) instrument to measure oxygenated haemoglobin ([oxy-Hb]) changes over the prefrontal cortex during a random number generation (RNG) task. In healthy controls, we found significant [oxy-Hb] increase in the bilateral dorsolateral (DLPFC; BA9 and BA46) and ventrolateral prefrontal cortex (VLPFC; BA44, 45 and 47). The patients with schizophrenia showed significantly smaller activation than the healthy controls in the same approximate regions. In the patient group, a smaller [oxy-Hb] increase in the right DLPFC region (BA9) was significantly correlated with earlier age at onset. NIRS can detect prefrontal cortical dysfunction associated with an executive task, which was coupled with earlier age at onset in schizophrenia. Multichannel NIRS, a non-invasive and user-friendly instrument, may be useful in evaluating cognitive function and social outcome in clinical settings in psychiatry. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

Kamiya, Kazunobu; Narita, Noriyuki; Iwaki, Sunao

2016-01-01

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

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

PubMed

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

1998-01-01

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

Reinforcement Learning Models and Their Neural Correlates: An Activation Likelihood Estimation Meta-Analysis

PubMed Central

Kumar, Poornima; Eickhoff, Simon B.; Dombrovski, Alexandre Y.

2015-01-01

Reinforcement learning describes motivated behavior in terms of two abstract signals. The representation of discrepancies between expected and actual rewards/punishments – prediction error – is thought to update the expected value of actions and predictive stimuli. Electrophysiological and lesion studies suggest that mesostriatal prediction error signals control behavior through synaptic modification of cortico-striato-thalamic networks. Signals in the ventromedial prefrontal and orbitofrontal cortex are implicated in representing expected value. To obtain unbiased maps of these representations in the human brain, we performed a meta-analysis of functional magnetic resonance imaging studies that employed algorithmic reinforcement learning models, across a variety of experimental paradigms. We found that the ventral striatum (medial and lateral) and midbrain/thalamus represented reward prediction errors, consistent with animal studies. Prediction error signals were also seen in the frontal operculum/insula, particularly for social rewards. In Pavlovian studies, striatal prediction error signals extended into the amygdala, while instrumental tasks engaged the caudate. Prediction error maps were sensitive to the model-fitting procedure (fixed or individually-estimated) and to the extent of spatial smoothing. A correlate of expected value was found in a posterior region of the ventromedial prefrontal cortex, caudal and medial to the orbitofrontal regions identified in animal studies. These findings highlight a reproducible motif of reinforcement learning in the cortico-striatal loops and identify methodological dimensions that may influence the reproducibility of activation patterns across studies. PMID:25665667

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

PubMed

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

2018-04-01

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

Brain Activity in Self- and Value-Related Regions in Response to Online Antismoking Messages Predicts Behavior Change

PubMed Central

Cooper, Nicole; Tompson, Steve; O’Donnell, Matthew Brook; Falk, Emily B.

2017-01-01

In this study, we combined approaches from media psychology and neuroscience to ask whether brain activity in response to online antismoking messages can predict smoking behavior change. In particular, we examined activity in subregions of the medial prefrontal cortex linked to self- and value-related processing, to test whether these neurocognitive processes play a role in message-consistent behavior change. We observed significant relationships between activity in both brain regions of interest and behavior change (such that higher activity predicted a larger reduction in smoking). Furthermore, activity in these brain regions predicted variance independent of traditional, theory-driven self-report metrics such as intention, self-efficacy, and risk perceptions. We propose that valuation is an additional cognitive process that should be investigated further as we search for a mechanistic explanation of the relationship between brain activity and media effects relevant to health behavior change. PMID:29057013

Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction

PubMed Central

Feng, Pan; Zheng, Yong

2016-01-01

Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. PMID:27013104

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

PubMed Central

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

2017-01-01

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral amygdala (BLA) and prelimbic (PL) medial prefrontal cortex (mPFC) have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally-connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task where in shock- and sucrose-predictive cues were simultaneously presented to induce competition. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, the majority of optogenetically-identified PL-projecting BLA neurons recorded encoded the shock-associated cue, and more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally, BLA→PL photostimulation increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. The BLA→PL circuit plays a critical role in governing the selection of behavioral responses in the face of competing signals. PMID:28436980

Predicting reading and mathematics from neural activity for feedback learning.

PubMed

Peters, Sabine; Van der Meulen, Mara; Zanolie, Kiki; Crone, Eveline A

2017-01-01

Although many studies use feedback learning paradigms to study the process of learning in laboratory settings, little is known about their relevance for real-world learning settings such as school. In a large developmental sample (N = 228, 8-25 years), we investigated whether performance and neural activity during a feedback learning task predicted reading and mathematics performance 2 years later. The results indicated that feedback learning performance predicted both reading and mathematics performance. Activity during feedback learning in left superior dorsolateral prefrontal cortex (DLPFC) predicted reading performance, whereas activity in presupplementary motor area/anterior cingulate cortex (pre-SMA/ACC) predicted mathematical performance. Moreover, left superior DLPFC and pre-SMA/ACC activity predicted unique variance in reading and mathematics ability over behavioral testing of feedback learning performance alone. These results provide valuable insights into the relationship between laboratory-based learning tasks and learning in school settings, and the value of neural assessments for prediction of school performance over behavioral testing alone. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Co-Variation of Peripheral Levels of miR-1202 and Brain Activity and Connectivity During Antidepressant Treatment.

PubMed

Lopez, Juan Pablo; Pereira, Fabricio; Richard-Devantoy, Stéphane; Berlim, Marcelo; Chachamovich, Eduardo; Fiori, Laura M; Niola, Paola; Turecki, Gustavo; Jollant, Fabrice

2017-09-01

MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of desvenlafaxine (50-100 mg die), 20 patients were scanned with 3T magnetic resonance imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition. Blood samples were collected at both time points. During resting state, lower baseline miR-1202 levels were predictive of increased connectivity from T0 to T8 between the posterior cingulate and the prefrontal, parietal, and occipital cortices. Changes in miR-1202 levels following desvenlafaxine treatment were negatively correlated with changes in activity in right precuneus within the default-mode network, and in connectivity between the posterior cingulate and the temporal and prefrontal cortices, and the precuneus. During the Go/NoGo task, baseline miR-1202 levels and changes in these levels were correlated with activity changes in different regions, including bilateral prefrontal, insular, cingulate, and temporal cortices, and left putamen and claustrum. Finally, secondary analyses in a subset of patients showed a trend for a significant correlation between miR-1202 levels and glutamate levels measured by spectroscopy. Changes in peripheral miR-1202 levels were therefore associated with changes in brain activity and connectivity in a network of brain regions associated with depression and antidepressant response. These effects may be mediated by the glutamatergic system.

Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder.

PubMed

Klumpp, Heide; Fitzgerald, Daniel A; Phan, K Luan

2013-08-01

Cognitive behavioral therapy (CBT) is "gold standard" psychotherapy for social anxiety disorder (SAD). Cognitive models posit that preferential processing of threat mediates excessive forms of anxiety, which is supported by exaggerated amygdala, insula, and cortical reactivity to threatening socio-emotional signals in SAD. However, little is known about neural predictors of CBT success or the mechanisms by which CBT exerts its therapeutic effects. Functional magnetic resonance imaging (fMRI) was conducted during responses to social signals of threat (fearful/angry faces) against positive signals (happy faces) in 14 patients with SAD before and after 12 weeks of CBT. For comparison, 14 healthy control (HC) participants also underwent two fMRI scans, 12 weeks apart. Whole-brain voxel-wise analyses showed therapeutic success was predicted by enhanced pre-treatment activation to threatening faces in higher-order visual (superior and middle temporal gyrus), cognitive, and emotion processing areas (dorsal anterior cingulate cortex, dorsomedial prefrontal cortex). Moreover, a group by time interaction was revealed in prefrontal regions (dorsomedial, medial gyrus) and insula. The interaction was driven by relatively greater activity during threat processing in SAD, which significantly reduced after CBT but did not significantly predict response to CBT. Therefore, pre-treatment cortical hyperactivity to social threat signals may serve as a prognostic indicator of CBT success in SAD. Collectively, CBT-related brain changes involved a reduction in activity in insula, prefrontal, and extrastriate regions. Results are consistent with cognitive models, which associate decreases in threat processing bias with recovery. Copyright © 2013 Elsevier Inc. All rights reserved.

Personality correlates (BAS-BIS), self-perception of social ranking, and cortical (alpha frequency band) modulation in peer-group comparison.

PubMed

Balconi, Michela; Pagani, Silvia

2014-06-22

The perception and interpretation of social hierarchies are a key part of our social life. In the present research we considered the activation of cortical areas, mainly the prefrontal cortex, related to social ranking perception in conjunction with some personality components (BAS - Behavioral Activation System - and BIS - Behavioral Inhibition System). In two experiments we manipulated the perceived superior/inferior status during a competitive cognitive task. Indeed, we created an explicit and strongly reinforced social hierarchy based on incidental rating in an attentional task. Specifically, a peer group comparison was undertaken and improved (Experiment 1) or decreased (Experiment 2) performance was artificially manipulated by the experimenter. For each experiment two groups were compared, based on a BAS and BIS dichotomy. Alpha band modulation in prefrontal cortex, behavioral measures (performance: error rate, ER; response times, RTs), and self-perceived ranking were considered. Repeated measures ANOVAs and regression analyses showed in Experiment 1 a significant improved cognitive performance (decreased ER and RTs) and higher self-perceived ranking in high-BAS participants. Moreover, their prefrontal activity was increased within the left side (alpha band decreasing). Conversely, in Experiment 2 a significant decreased cognitive performance (increased ER and RTs) and lower self-perceived ranking was observed in higher-BIS participants. Their prefrontal right activity was increased in comparison with higher BAS. The regression analyses confirmed the significant predictive role of alpha band modulation with respect of subjects' performance and self-perception of social ranking, differently for BAS/BIS components. The present results suggest that social status perception is directly modulated by cortical activity and personality correlates. Copyright © 2014 Elsevier Inc. All rights reserved.

Response to learned threat: an fMRI study in adolescent and adult anxiety

PubMed Central

Britton, Jennifer C.; Grillon, Christian; Lissek, Shmuel; Norcross, Maxine A.; Szuhany, Kristin L.; Chen, Gang; Ernst, Monique; Nelson, Eric E.; Leibenluft, Ellen; Shechner, Tomer; Pine, Daniel S.

2013-01-01

Objective Poor threat-safety discrimination reflects prefrontal cortex dysfunction in adult anxiety disorders. While adolescent anxiety disorders are impairing and predict high risk for adult anxiety disorders, no prior study examines neural correlates of threat-safety discrimination in this group. The current study compares prefrontal cortex function in anxious and healthy adolescents and adults following conditioning and extinction, processes requiring threat-safety learning. Method Anxious and healthy adolescents and adults (n=114) completed fear conditioning and extinction in the clinic. Conditioned stimuli (CS+) were neutral faces, paired with an aversive scream. Physiological and subjective data were acquired. Several weeks later, 82 participants viewed the CS+ and morphed images resembling the CS+ in a magnetic resonance imaging (MRI) scanner. During scanning, participants made difficult threat-safety discriminations while appraising threat and explicit memory of the CS+. Results During conditioning and extinction, anxious groups reported more fear than healthy groups, but patient groups did not differ on physiology. During imaging, both anxious adolescents and adults exhibited lower sub-genual anterior cingulate (sgACC) activation than healthy peers, specifically when appraising threat. In ventromedial prefrontal cortex (vmPFC), relative to their age-matched peer groups, anxious adults exhibited reduced activation when appraising threat, whereas anxious adolescents exhibited a U-shaped pattern of activation, with greater activation to the most extreme CS and CS−. Conclusions Two regions of the prefrontal cortex are involved in anxiety disorders. Reduced sgACC engagement is a shared feature in adult and adolescent anxiety disorders, but vmPFC dysfunction is age-specific. The unique U-shaped pattern of vmPFC activation in many anxious adolescents could reflect heightened sensitivity to threat and safety conditions. How variations in the pattern relate to later risk for adult illness remains to be determined. PMID:23929092

Prefrontal Cortex Structure Predicts Training-Induced Improvements in Multitasking Performance.

PubMed

Verghese, Ashika; Garner, K G; Mattingley, Jason B; Dux, Paul E

2016-03-02

The ability to perform multiple, concurrent tasks efficiently is a much-desired cognitive skill, but one that remains elusive due to the brain's inherent information-processing limitations. Multitasking performance can, however, be greatly improved through cognitive training (Van Selst et al., 1999, Dux et al., 2009). Previous studies have examined how patterns of brain activity change following training (for review, see Kelly and Garavan, 2005). Here, in a large-scale human behavioral and imaging study of 100 healthy adults, we tested whether multitasking training benefits, assessed using a standard dual-task paradigm, are associated with variability in brain structure. We found that the volume of the rostral part of the left dorsolateral prefrontal cortex (DLPFC) predicted an individual's response to training. Critically, this association was observed exclusively in a task-specific training group, and not in an active-training control group. Our findings reveal a link between DLPFC structure and an individual's propensity to gain from training on a task that taps the limits of cognitive control. Cognitive "brain" training is a rapidly growing, multibillion dollar industry (Hayden, 2012) that has been touted as the panacea for a variety of disorders that result in cognitive decline. A key process targeted by such training is "cognitive control." Here, we combined an established cognitive control measure, multitasking ability, with structural brain imaging in a sample of 100 participants. Our goal was to determine whether individual differences in brain structure predict the extent to which people derive measurable benefits from a cognitive training regime. Ours is the first study to identify a structural brain marker-volume of left hemisphere dorsolateral prefrontal cortex-associated with the magnitude of multitasking performance benefits induced by training at an individual level. Copyright © 2016 the authors 0270-6474/16/362638-08$15.00/0.

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

PubMed

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

2011-03-01

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

Neural Priming in Human Frontal Cortex: Multiple Forms of Learning Reduce Demands on the Prefrontal Executive System

ERIC Educational Resources Information Center

Race, Elizabeth A.; Shanker, Shanti; Wagner, Anthony D.

2009-01-01

Past experience is hypothesized to reduce computational demands in PFC by providing bottom-up predictive information that informs subsequent stimulus-action mapping. The present fMRI study measured cortical activity reductions ("neural priming"/"repetition suppression") during repeated stimulus classification to investigate the mechanisms through…

Predicting Motivation: Computational Models of PFC Can Explain Neural Coding of Motivation and Effort-based Decision-making in Health and Disease.

PubMed

Vassena, Eliana; Deraeve, James; Alexander, William H

2017-10-01

Human behavior is strongly driven by the pursuit of rewards. In daily life, however, benefits mostly come at a cost, often requiring that effort be exerted to obtain potential benefits. Medial PFC (MPFC) and dorsolateral PFC (DLPFC) are frequently implicated in the expectation of effortful control, showing increased activity as a function of predicted task difficulty. Such activity partially overlaps with expectation of reward and has been observed both during decision-making and during task preparation. Recently, novel computational frameworks have been developed to explain activity in these regions during cognitive control, based on the principle of prediction and prediction error (predicted response-outcome [PRO] model [Alexander, W. H., & Brown, J. W. Medial prefrontal cortex as an action-outcome predictor. Nature Neuroscience, 14, 1338-1344, 2011], hierarchical error representation [HER] model [Alexander, W. H., & Brown, J. W. Hierarchical error representation: A computational model of anterior cingulate and dorsolateral prefrontal cortex. Neural Computation, 27, 2354-2410, 2015]). Despite the broad explanatory power of these models, it is not clear whether they can also accommodate effects related to the expectation of effort observed in MPFC and DLPFC. Here, we propose a translation of these computational frameworks to the domain of effort-based behavior. First, we discuss how the PRO model, based on prediction error, can explain effort-related activity in MPFC, by reframing effort-based behavior in a predictive context. We propose that MPFC activity reflects monitoring of motivationally relevant variables (such as effort and reward), by coding expectations and discrepancies from such expectations. Moreover, we derive behavioral and neural model-based predictions for healthy controls and clinical populations with impairments of motivation. Second, we illustrate the possible translation to effort-based behavior of the HER model, an extended version of PRO model based on hierarchical error prediction, developed to explain MPFC-DLPFC interactions. We derive behavioral predictions that describe how effort and reward information is coded in PFC and how changing the configuration of such environmental information might affect decision-making and task performance involving motivation.

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

PubMed

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

2016-01-01

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

Tempering Proactive Cognitive Control by Transcranial Direct Current Stimulation of the Right (but Not the Left) Lateral Prefrontal Cortex

PubMed Central

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 that both prefrontal regions differentially contribute to the adjustment of cognitive control modes. tDCS of the left-DLPFC failed to modulate cognitive control. These results partially support the predictions derived from the dual mechanisms of control account. PMID:28588441

Cerebral responses to local and global auditory novelty under general anesthesia

PubMed Central

Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir

2017-01-01

Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices. PMID:27502046

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

PubMed Central

Spühler, Isabelle Ayumi; Hauri, Andreas

2013-01-01

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

Load-related brain activation predicts spatial working memory performance in youth aged 9–12 and is associated with executive function at earlier ages

PubMed Central

Huang, Anna S.; Klein, Daniel N.; Leung, Hoi-Chung

2015-01-01

Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9–12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. PMID:26562059

Load-related brain activation predicts spatial working memory performance in youth aged 9-12 and is associated with executive function at earlier ages.

PubMed

Huang, Anna S; Klein, Daniel N; Leung, Hoi-Chung

2016-02-01

Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9-12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electrophysiological correlates reflect the integration of model-based and model-free decision information.

PubMed

Eppinger, Ben; Walter, Maik; Li, Shu-Chen

2017-04-01

In this study, we investigated the interplay of habitual (model-free) and goal-directed (model-based) decision processes by using a two-stage Markov decision task in combination with event-related potentials (ERPs) and computational modeling. To manipulate the demands on model-based decision making, we applied two experimental conditions with different probabilities of transitioning from the first to the second stage of the task. As we expected, when the stage transitions were more predictable, participants showed greater model-based (planning) behavior. Consistent with this result, we found that stimulus-evoked parietal (P300) activity at the second stage of the task increased with the predictability of the state transitions. However, the parietal activity also reflected model-free information about the expected values of the stimuli, indicating that at this stage of the task both types of information are integrated to guide decision making. Outcome-related ERP components only reflected reward-related processes: Specifically, a medial prefrontal ERP component (the feedback-related negativity) was sensitive to negative outcomes, whereas a component that is elicited by reward (the feedback-related positivity) increased as a function of positive prediction errors. Taken together, our data indicate that stimulus-locked parietal activity reflects the integration of model-based and model-free information during decision making, whereas feedback-related medial prefrontal signals primarily reflect reward-related decision processes.

Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

NASA Astrophysics Data System (ADS)

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

2004-10-01

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

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.

PubMed

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

2004-10-29

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

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI.

PubMed

Migo, E M; O'Daly, O; Mitterschiffthaler, M; Antonova, E; Dawson, G R; Dourish, C T; Craig, K J; Simmons, A; Wilcock, G K; McCulloch, E; Jackson, S H D; Kopelman, M D; Williams, S C R; Morris, R G

2016-01-01

Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

Cultural modulation of self-referential brain activity for personality traits and social identities.

PubMed

Sul, Sunhae; Choi, Incheol; Kang, Pyungwon

2012-01-01

Cross-cultural studies have shown that personality traits are less central and social identities are more important to the selfhood of collectivistic people. However, most cultural neuroscience studies using the self-reference effect (SRE) paradigm have only used personality traits to explore cultural differences in the neural circuits of self-referential processes. In the present study, we used both personality traits and social identities as stimuli in the SRE paradigm and investigated whether and how one's cultural orientation (i.e., individualism vs. collectivism) affects the SRE in the brain. The results showed that the medial prefrontal cortex, anterior cingulate, bilateral temporoparietal regions, and precuneus were involved in self-representation for both personality traits and social identities. Importantly, cultural orientation predicted differential activation patterns in these regions. Collectivists showed stronger activation in the left temporoparietal regions than individualists, who mainly recruited the medial prefrontal regions. Our findings suggest that the personal and social self share common neural substrates, the activation of which can be modulated by one's cultural orientation.

Prefrontal contributions to metacognition in perceptual decision-making

PubMed Central

Fleming, Stephen M.; Huijgen, Josefien; Dolan, Raymond J.

2012-01-01

Neuroscience has made considerable progress in understanding the neural substrates supporting cognitive performance in a number of domains, including memory, perception and decision-making. In contrast, how the human brain generates metacognitive awareness of task performance remains unclear. Here, we address this question by asking participants to perform perceptual decisions while providing concurrent metacognitive reports, during fMRI scanning. We show that activity in right rostrolateral prefrontal cortex (rlPFC) satisfies three constraints for a role in metacognitive aspects of decision-making. Right rlPFC showed greater activity during self-report compared to a matched control condition; activity in this region correlated with reported confidence; and the strength of the relationship between activity and confidence predicted metacognitive ability across individuals. In addition, functional connectivity between right rlPFC and both contralateral PFC and visual cortex increased during metacognitive reports. We discuss these findings in a theoretical framework where rlPFC re-represents object-level decision uncertainty to facilitate metacognitive report. PMID:22553018

Prefrontal Engagement during Source Memory Retrieval Depends on the Prior Encoding Task

PubMed Central

Kuo, Trudy Y.; Van Petten, Cyma

2008-01-01

The prefrontal cortex is strongly engaged by some, but not all, episodic memory tests. Prior work has shown that source recognition tests—those that require memory for conjunctions of studied attributes—yield deficient performance in patients with prefrontal damage and greater prefrontal activity in healthy subjects, as compared to simple recognition tests. Here, we tested the hypothesis that there is no intrinsic relationship between the prefrontal cortex and source memory, but that the prefrontal cortex is engaged by the demand to retrieve weakly encoded relationships. Subjects attempted to remember object/color conjunctions after an encoding task that focused on object identity alone, and an integrative encoding task that encouraged attention to object/color relationships. After the integrative encoding task, the late prefrontal brain electrical activity that typically occurs in source memory tests was eliminated. Earlier brain electrical activity related to successful recognition of the objects was unaffected by the nature of prior encoding. PMID:16839287

Reward-dependent learning in neuronal networks for planning and decision making.

PubMed

Dehaene, S; Changeux, J P

2000-01-01

Neuronal network models have been proposed for the organization of evaluation and decision processes in prefrontal circuitry and their putative neuronal and molecular bases. The models all include an implementation and simulation of an elementary reward mechanism. Their central hypothesis is that tentative rules of behavior, which are coded by clusters of active neurons in prefrontal cortex, are selected or rejected based on an evaluation by this reward signal, which may be conveyed, for instance, by the mesencephalic dopaminergic neurons with which the prefrontal cortex is densely interconnected. At the molecular level, the reward signal is postulated to be a neurotransmitter such as dopamine, which exerts a global modulatory action on prefrontal synaptic efficacies, either via volume transmission or via targeted synaptic triads. Negative reinforcement has the effect of destabilizing the currently active rule-coding clusters; subsequently, spontaneous activity varies again from one cluster to another, giving the organism the chance to discover and learn a new rule. Thus, reward signals function as effective selection signals that either maintain or suppress currently active prefrontal representations as a function of their current adequacy. Simulations of this variation-selection have successfully accounted for the main features of several major tasks that depend on prefrontal cortex integrity, such as the delayed-response test, the Wisconsin card sorting test, the Tower of London test and the Stroop test. For the more complex tasks, we have found it necessary to supplement the external reward input with a second mechanism that supplies an internal reward; it consists of an auto-evaluation loop which short-circuits the reward input from the exterior. This allows for an internal evaluation of covert motor intentions without actualizing them as behaviors, by simply testing them covertly by comparison with memorized former experiences. This element of architecture gives access to enhanced rates of learning via an elementary process of internal or covert mental simulation. We have recently applied these ideas to a new model, developed with M. Kerszberg, which hypothesizes that prefrontal cortex and its reward-related connections contribute crucially to conscious effortful tasks. This model distinguishes two main computational spaces within the human brain: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative and attentional processors. We postulate that workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice; they selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously co-activated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. This model makes predictions concerning the spatio-temporal activation patterns during brain imaging of cognitive tasks, particularly concerning the conditions of activation of dorsolateral prefrontal cortex and anterior cingulate, their relation to reward mechanisms, and their specific reaction during error processing.

Predicting the integration of overlapping memories by decoding mnemonic processing states during learning

PubMed Central

Richter, Franziska R.; Chanales, Avi J. H.; Kuhl, Brice A.

2015-01-01

The hippocampal memory system is thought to alternate between two opposing processing states: encoding and retrieval. When present experience overlaps with past experience, this creates a potential tradeoff between encoding the present and retrieving the past. This tradeoff may be resolved by memory integration—that is, by forming a mnemonic representation that links present experience with overlapping past experience. Here, we used fMRI decoding analyses to predict when—and establish how—past and present experiences become integrated in memory. In an initial experiment, we alternately instructed subjects to adopt encoding, retrieval or integration states during overlapping learning. We then trained across-subject pattern classifiers to ‘read out’ the instructed processing states from fMRI activity patterns. We show that an integration state was clearly dissociable from encoding or retrieval states. Moreover, trial-by-trial fluctuations in decoded evidence for an integration state during learning reliably predicted behavioral expressions of successful memory integration. Strikingly, the decoding algorithm also successfully predicted specific instances of spontaneous memory integration in an entirely independent sample of subjects for whom processing state instructions were not administered. Finally, we show that medial prefrontal cortex and hippocampus differentially contribute to encoding, retrieval, and integration states: whereas hippocampus signals the tradeoff between encoding vs. retrieval states, medial prefrontal cortex actively represents past experience in relation to new learning. PMID:26327243

Similar patterns of neural activity predict memory function during encoding and retrieval.

PubMed

Kragel, James E; Ezzyat, Youssef; Sperling, Michael R; Gorniak, Richard; Worrell, Gregory A; Berry, Brent M; Inman, Cory; Lin, Jui-Jui; Davis, Kathryn A; Das, Sandhitsu R; Stein, Joel M; Jobst, Barbara C; Zaghloul, Kareem A; Sheth, Sameer A; Rizzuto, Daniel S; Kahana, Michael J

2017-07-15

Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2.

PubMed

Taurisano, Paolo; Romano, Raffaella; Mancini, Marina; Giorgio, Annabella Di; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Quarto, Tiziana; Gelao, Barbara; Porcelli, Annamaria; Papazacharias, Apostolos; Ursini, Gianluca; Caforio, Grazia; Masellis, Rita; Niccoli-Asabella, Artor; Todarello, Orlando; Popolizio, Teresa; Rubini, Giuseppe; Blasi, Giuseppe; Bertolino, Alessandro

2014-01-01

"Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.

Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2

PubMed Central

Taurisano, Paolo; Romano, Raffaella; Mancini, Marina; Giorgio, Annabella Di; Antonucci, Linda A.; Fazio, Leonardo; Rampino, Antonio; Quarto, Tiziana; Gelao, Barbara; Porcelli, Annamaria; Papazacharias, Apostolos; Ursini, Gianluca; Caforio, Grazia; Masellis, Rita; Niccoli-Asabella, Artor; Todarello, Orlando; Popolizio, Teresa; Rubini, Giuseppe; Blasi, Giuseppe; Bertolino, Alessandro

2014-01-01

“Schizotypy” is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [123I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum. PMID:25071490

Imitating expressions: emotion-specific neural substrates in facial mimicry.

PubMed

Lee, Tien-Wen; Josephs, Oliver; Dolan, Raymond J; Critchley, Hugo D

2006-09-01

Intentionally adopting a discrete emotional facial expression can modulate the subjective feelings corresponding to that emotion; however, the underlying neural mechanism is poorly understood. We therefore used functional brain imaging (functional magnetic resonance imaging) to examine brain activity during intentional mimicry of emotional and non-emotional facial expressions and relate regional responses to the magnitude of expression-induced facial movement. Eighteen healthy subjects were scanned while imitating video clips depicting three emotional (sad, angry, happy), and two 'ingestive' (chewing and licking) facial expressions. Simultaneously, facial movement was monitored from displacement of fiducial markers (highly reflective dots) on each subject's face. Imitating emotional expressions enhanced activity within right inferior prefrontal cortex. This pattern was absent during passive viewing conditions. Moreover, the magnitude of facial movement during emotion-imitation predicted responses within right insula and motor/premotor cortices. Enhanced activity in ventromedial prefrontal cortex and frontal pole was observed during imitation of anger, in ventromedial prefrontal and rostral anterior cingulate during imitation of sadness and in striatal, amygdala and occipitotemporal during imitation of happiness. Our findings suggest a central role for right inferior frontal gyrus in the intentional imitation of emotional expressions. Further, by entering metrics for facial muscular change into analysis of brain imaging data, we highlight shared and discrete neural substrates supporting affective, action and social consequences of somatomotor emotional expression.

The selfless mind: How prefrontal involvement in mentalizing with similar and dissimilar others shapes empathy and prosocial behavior.

PubMed

Majdandžić, Jasminka; Amashaufer, Sandra; Hummer, Allan; Windischberger, Christian; Lamm, Claus

2016-12-01

Engaging in mentalizing, i.e., reflecting on others' thoughts, beliefs and feelings, is known to facilitate later empathy and prosocial behavior. Activation in dorsomedial prefrontal (dmPFC) areas during mentalizing has been shown to predict the extent of prosocial behavior. It is unclear, however, what cognitive process drives these effects: a simulation process in which the own mental states are used as a proxy for those of others (self-projection) or an effortful other-enhancement process in which one's own perspective is overridden. In this fMRI study we examined the effects of mentalizing with similar and dissimilar others on behavioral and brain measures of empathy and prosocial behavior, to assess which cognitive process mediates the facilitative effects of mentalizing. Participants had to mentalize with two fictitious target persons, one of whom was manipulated to have similar thoughts and beliefs as the participant, while the other had dissimilar mental states. We then assessed participants' behavioral and neural responses during an empathy for pain task and a prosocial behavior task. Similarity between participant and target person increased empathy and affiliation ratings, and mentalizing with dissimilar persons evoked increased activation in ventrolateral prefrontal cortex, the extent of which was inversely related with bias towards the similar person in empathy. Responses in two dmPFC regions were also predictive of later variations in subsequent empathy and prosocial behavior, either predicting overall prosociality and empathic concern (lateral dmPFC), or predicting reduced empathic bias towards the similar person and a lower response to self-related stressors in pain matrix areas (medial dmPFC). This pattern of results suggests that generating and enhancing other-related representations while overcoming one's own perspective, rather than enhanced recruitment of self-projection processes, is driving the facilitative effects of mentalizing on later empathic and prosocial responses. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-01-01

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

Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction.

PubMed

Feng, Pan; Zheng, Yong; Feng, Tingyong

2016-06-01

Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson's disease.

PubMed

Weiss, Daniel; Klotz, Rosa; Govindan, Rathinaswamy B; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko; Gharabaghi, Alireza

2015-03-01

Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson's disease. Here, we set out to address the motor network activity and synchronization in Parkinson's disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson's disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with 'stimulation on' compared to 'stimulation off' on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With 'stimulation on', interhemispheric cortico-cortical coherence in the beta band was significantly attenuated over the bilateral sensorimotor areas. Similarly, the global cortico-cortical phase synchronization was attenuated, and the topographic differentiation revealed stronger desynchronization over the (ipsilateral) right-hemispheric prefrontal, premotor and sensorimotor areas compared to 'stimulation off'. We further demonstrated that the cortico-cortical phase synchronization was largely dominated by genuine neuronal coupling. The clinical improvement with 'stimulation on' compared to 'stimulation off' could be predicted from this cortical decoupling with multiple regressions, and the reduction of synchronization over the right prefrontal area showed a linear univariate correlation with clinical improvement. Our study demonstrates wide-spread activity and synchronization modulations of the cortical motor network, and highlights subthalamic stimulation as a network-modulating therapy. Accordingly, subthalamic stimulation may release bilateral cortical computational resources by facilitating movement-related desynchronization. Moreover, the subthalamic nucleus is critical to balance inhibitory and facilitatory cortical players within the motor program. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson’s disease

PubMed Central

Klotz, Rosa; Govindan, Rathinaswamy B.; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko

2015-01-01

Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson’s disease. Here, we set out to address the motor network activity and synchronization in Parkinson’s disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson’s disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with ‘stimulation on’ compared to ‘stimulation off’ on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With ‘stimulation on’, interhemispheric cortico-cortical coherence in the beta band was significantly attenuated over the bilateral sensorimotor areas. Similarly, the global cortico-cortical phase synchronization was attenuated, and the topographic differentiation revealed stronger desynchronization over the (ipsilateral) right-hemispheric prefrontal, premotor and sensorimotor areas compared to ‘stimulation off’. We further demonstrated that the cortico-cortical phase synchronization was largely dominated by genuine neuronal coupling. The clinical improvement with ‘stimulation on’ compared to ‘stimulation off’ could be predicted from this cortical decoupling with multiple regressions, and the reduction of synchronization over the right prefrontal area showed a linear univariate correlation with clinical improvement. Our study demonstrates wide-spread activity and synchronization modulations of the cortical motor network, and highlights subthalamic stimulation as a network-modulating therapy. Accordingly, subthalamic stimulation may release bilateral cortical computational resources by facilitating movement-related desynchronization. Moreover, the subthalamic nucleus is critical to balance inhibitory and facilitatory cortical players within the motor program. PMID:25558877

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

PubMed Central

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

2016-01-01

Objective Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Methods Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein’s Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Results Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. Conclusions These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition. PMID:27798669

Neurobiological mechanisms underlying the blocking effect in aversive learning.

PubMed

Eippert, Falk; Gamer, Matthias; Büchel, Christian

2012-09-19

Current theories of classical conditioning assume that learning depends on the predictive relationship between events, not just on their temporal contiguity. Here we employ the classic experiment substantiating this reasoning-the blocking paradigm-in combination with functional magnetic resonance imaging (fMRI) to investigate whether human amygdala responses in aversive learning conform to these assumptions. In accordance with blocking, we demonstrate that significantly stronger behavioral and amygdala responses are evoked by conditioned stimuli that are predictive of the unconditioned stimulus than by conditioned stimuli that have received the same pairing with the unconditioned stimulus, yet have no predictive value. When studying the development of this effect, we not only observed that it was related to the strength of previous conditioned responses, but also that predictive compared with nonpredictive conditioned stimuli received more overt attention, as measured by fMRI-concurrent eye tracking, and that this went along with enhanced amygdala responses. We furthermore observed that prefrontal regions play a role in the development of the blocking effect: ventromedial prefrontal cortex (subgenual anterior cingulate) only exhibited responses when conditioned stimuli had to be established as nonpredictive for an outcome, whereas dorsolateral prefrontal cortex also showed responses when conditioned stimuli had to be established as predictive. Most importantly, dorsolateral prefrontal cortex connectivity to amygdala flexibly switched between positive and negative coupling, depending on the requirements posed by predictive relationships. Together, our findings highlight the role of predictive value in explaining amygdala responses and identify mechanisms that shape these responses in human fear conditioning.

Top-down modulation of visual processing and knowledge after 250 ms supports object constancy of category decisions

PubMed Central

Schendan, Haline E.; Ganis, Giorgio

2015-01-01

People categorize objects more slowly when visual input is highly impoverished instead of optimal. While bottom-up models may explain a decision with optimal input, perceptual hypothesis testing (PHT) theories implicate top-down processes with impoverished input. Brain mechanisms and the time course of PHT are largely unknown. This event-related potential study used a neuroimaging paradigm that implicated prefrontal cortex in top-down modulation of occipitotemporal cortex. Subjects categorized more impoverished and less impoverished real and pseudo objects. PHT theories predict larger impoverishment effects for real than pseudo objects because top-down processes modulate knowledge only for real objects, but different PHT variants predict different timing. Consistent with parietal-prefrontal PHT variants, around 250 ms, the earliest impoverished real object interaction started on an N3 complex, which reflects interactive cortical activity for object cognition. N3 impoverishment effects localized to both prefrontal and occipitotemporal cortex for real objects only. The N3 also showed knowledge effects by 230 ms that localized to occipitotemporal cortex. Later effects reflected (a) word meaning in temporal cortex during the N400, (b) internal evaluation of prior decision and memory processes and secondary higher-order memory involving anterotemporal parts of a default mode network during posterior positivity (P600), and (c) response related activity in posterior cingulate during an anterior slow wave (SW) after 700 ms. Finally, response activity in supplementary motor area during a posterior SW after 900 ms showed impoverishment effects that correlated with RTs. Convergent evidence from studies of vision, memory, and mental imagery which reflects purely top-down inputs, indicates that the N3 reflects the critical top-down processes of PHT. A hybrid multiple-state interactive, PHT and decision theory best explains the visual constancy of object cognition. PMID:26441701

DRD2/CHRNA5 Interaction on Prefrontal Biology and Physiology during Working Memory

PubMed Central

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

2014-01-01

Background Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. Methods A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. Results We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. Conclusions The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5. PMID:24819610

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

PubMed

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

2014-01-01

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

Development of Active Control within Working Memory: Active Retrieval versus Monitoring in Children

ERIC Educational Resources Information Center

Blain-Brière, Bénédicte; Bouchard, Caroline; Bigras, Nathalie; Cadoret, Geneviève

2014-01-01

This study aimed to compare children's performance on two mnemonic functions that engage the lateral prefrontal cortex. Brain imaging studies in adults have shown that the mid-ventrolateral prefrontal cortex is specifically involved in active controlled retrieval, and the mid-dorsolateral prefrontal cortex is specifically involved in monitoring…

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

PubMed Central

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

2015-01-01

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

Effects of mandibular retrusive deviation on prefrontal cortex activation: a functional near-infrared spectroscopy study.

PubMed

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

2015-01-01

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

Dynamic neural activity during stress signals resilient coping

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

2016-01-01

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

Neural correlates of working memory development in adolescent primates

PubMed Central

Zhou, Xin; Zhu, Dantong; Qi, Xue-Lian; Li, Sihai; King, Samson G.; Salinas, Emilio; Stanford, Terrence R.; Constantinidis, Christos

2016-01-01

Working memory ability matures after puberty, in parallel with structural changes in the prefrontal cortex, but little is known about how changes in prefrontal neuronal activity mediate this cognitive improvement in primates. To address this issue, we compare behavioural performance and neurophysiological activity in monkeys as they transitioned from puberty into adulthood. Here we report that monkeys perform working memory tasks reliably during puberty and show modest improvement in adulthood. The adult prefrontal cortex is characterized by increased activity during the delay period of the task but no change in the representation of stimuli. Activity evoked by distracting stimuli also decreases in the adult prefrontal cortex. The increase in delay period activity relative to the baseline activity of prefrontal neurons is the best correlate of maturation and is not merely a consequence of improved performance. Our results reveal neural correlates of the working memory improvement typical of primate adolescence. PMID:27827365

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

PubMed Central

Sickinger, Stephanie; Haeussinger, Florian B.; Laeger, Inga; Arolt, Volker; Zwanzger, Peter; Fallgatter, Andreas J.

2014-01-01

Objectives. Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Conclusion. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed. PMID:24757668

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

PubMed

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

2014-01-01

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

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

PubMed Central

Moriguchi, Yoshiya

2014-01-01

Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions. PMID:25436155

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

PubMed

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior

PubMed Central

Grosenick, Logan; Warden, Melissa R.; Amatya, Debha; Katovich, Kiefer; Mehta, Hershel; Patenaude, Brian; Ramakrishnan, Charu; Kalanithi, Paul; Etkin, Amit; Knutson, Brian; Glover, Gary H.; Deisseroth, Karl

2016-01-01

Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions. PMID:26722001

Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness.

PubMed

Hubbard, Nicholas A; Hutchison, Joanna L; Motes, Michael A; Shokri-Kojori, Ehsan; Bennett, Ilana J; Brigante, Ryan M; Haley, Robert W; Rypma, Bart

2014-05-01

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness

PubMed Central

Hubbard, Nicholas A.; Hutchison, Joanna L.; Motes, Michael A.; Shokri-Kojori, Ehsan; Bennett, Ilana J.; Brigante, Ryan M.; Haley, Robert W.; Rypma, Bart

2015-01-01

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM. PMID:25767746

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

PubMed

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

2017-06-01

To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or represented within the prefrontal cortex in a cryptic code. Copyright © 2017 the American Physiological Society.

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-related dopamine hyperfunction. PMID:24899715

Reward inference by primate prefrontal and striatal neurons.

PubMed

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

2014-01-22

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

Reward Inference by Primate Prefrontal and Striatal Neurons

PubMed Central

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

2014-01-01

The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus–reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning. PMID:24453328

Neuroimaging studies of practice-related change: fMRI and meta-analytic evidence of a domain-general control network for learning.

PubMed

Chein, Jason M; Schneider, Walter

2005-12-01

Functional magnetic resonance imaging and a meta-analysis of prior neuroimaging studies were used to characterize cortical changes resulting from extensive practice and to evaluate a dual-processing account of the neural mechanisms underlying human learning. Three core predictions of the dual processing theory are evaluated: 1) that practice elicits generalized reductions in regional activity by reducing the load on the cognitive control mechanisms that scaffold early learning; 2) that these control mechanisms are domain-general; and 3) that no separate processing pathway emerges as skill develops. To evaluate these predictions, a meta-analysis of prior neuroimaging studies and a within-subjects fMRI experiment contrasting unpracticed to practiced performance in a paired-associate task were conducted. The principal effect of practice was found to be a reduction in the extent and magnitude of activity in a cortical network spanning bilateral dorsal prefrontal, left ventral prefrontal, medial frontal (anterior cingulate), left insular, bilateral parietal, and occipito-temporal (fusiform) areas. These activity reductions are shown to occur in common regions across prior neuroimaging studies and for both verbal and nonverbal paired-associate learning in the present fMRI experiment. The implicated network of brain regions is interpreted as a domain-general system engaged specifically to support novice, but not practiced, performance.

Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use.

PubMed

Taurisano, Paolo; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Romano, Raffaella; Porcelli, Annamaria; Masellis, Rita; Colizzi, Marco; Quarto, Tiziana; Torretta, Silvia; Di Giorgio, Annabella; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

2016-08-01

The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prefrontal Recruitment During Social Rejection Predicts Greater Subsequent Self-Regulatory Imbalance and Impairment: Neural and Longitudinal Evidence

PubMed Central

Chester, David S.; DeWall, C. Nathan

2014-01-01

Social rejection impairs self-regulation, yet the neural mechanisms underlying this relationship remain unknown. The right ventrolateral prefrontal cortex (rVLPFC) facilitates self-regulation and plays a robust role in regulating the distress of social rejection. However, recruiting this region’s inhibitory function during social rejection may come at a self-regulatory cost. As supported by prominent theories of self-regulation, we hypothesized that greater rVLPFC recruitment during rejection would predict a subsequent self-regulatory imbalance that favored reflexive impulses (i.e., cravings), which would then impair self-regulation. Supporting our hypotheses, rVLPFC activation during social rejection was associated with greater subsequent nucleus accumbens (NAcc) activation and lesser functional connectivity between the NAcc and rVLPFC to appetitive cues. Over seven days, the effect of daily felt rejection on daily self-regulatory impairment was exacerbated among participants who showed a stronger rVLPFC response to social rejection. This interactive effect was mirrored in the effect of daily felt rejection on heightened daily alcohol cravings. Our findings suggest that social rejection likely impairs self-regulation by recruiting the rVLPFC, which then tips the regulatory balance towards reward-based impulses. PMID:25094019

Prefrontal recruitment during social rejection predicts greater subsequent self-regulatory imbalance and impairment: neural and longitudinal evidence.

PubMed

Chester, David S; DeWall, C Nathan

2014-11-01

Social rejection impairs self-regulation, yet the neural mechanisms underlying this relationship remain unknown. The right ventrolateral prefrontal cortex (rVLPFC) facilitates self-regulation and plays a robust role in regulating the distress of social rejection. However, recruiting this region's inhibitory function during social rejection may come at a self-regulatory cost. As supported by prominent theories of self-regulation, we hypothesized that greater rVLPFC recruitment during rejection would predict a subsequent self-regulatory imbalance that favored reflexive impulses (i.e., cravings), which would then impair self-regulation. Supporting our hypotheses, rVLPFC activation during social rejection was associated with greater subsequent nucleus accumbens (NAcc) activation and lesser functional connectivity between the NAcc and rVLPFC to appetitive cues. Over seven days, the effect of daily felt rejection on daily self-regulatory impairment was exacerbated among participants who showed a stronger rVLPFC response to social rejection. This interactive effect was mirrored in the effect of daily felt rejection on heightened daily alcohol cravings. Our findings suggest that social rejection likely impairs self-regulation by recruiting the rVLPFC, which then tips the regulatory balance towards reward-based impulses. Copyright © 2014 Elsevier Inc. All rights reserved.

COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias.

PubMed

Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M; Dobson-Stone, Carol; Paul, Robert H; Gordon, Evian; Schofield, Peter R

2010-11-15

Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders. Copyright 2010 Elsevier Inc. All rights reserved.

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

PubMed

Major, Alex J; Vijayraghavan, Susheel; Everling, Stefan

2018-01-31

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system. Copyright © 2018 the authors 0270-6474/18/381137-14$15.00/0.

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

PubMed

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

2014-01-01

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

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…

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

PubMed Central

Watanabe, Takamitsu; Yahata, Noriaki; Abe, Osamu; Kuwabara, Hitoshi; Inoue, Hideyuki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Sasaki, Hiroki; Gonoi, Wataru; Murakami, Mizuho; Katsura, Masaki; Kunimatsu, Akira; Kawakubo, Yuki; Matsuzaki, Hideo; Tsuchiya, Kenji J.; Kato, Nobumasa; Kano, Yukiko; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori

2012-01-01

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information. PMID:22745788

Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

PubMed

Weiss, K L; Welsh, R C; Eldevik, P; Bieliauskas, L A; Steinberg, B A

2001-12-01

The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P < 2.0 x 10(-12)) and maintained this knowledge at I week. The encoding and recall paradigms elicited distributed networks of brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

Interactions between the nucleus accumbens and auditory cortices predict music reward value.

PubMed

Salimpoor, Valorie N; van den Bosch, Iris; Kovacevic, Natasa; McIntosh, Anthony Randal; Dagher, Alain; Zatorre, Robert J

2013-04-12

We used functional magnetic resonance imaging to investigate neural processes when music gains reward value the first time it is heard. The degree of activity in the mesolimbic striatal regions, especially the nucleus accumbens, during music listening was the best predictor of the amount listeners were willing to spend on previously unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value, which was instead predicted by increasing functional connectivity of these regions with the nucleus accumbens as the reward value increased. Thus, aesthetic rewards arise from the interaction between mesolimbic reward circuitry and cortical networks involved in perceptual analysis and valuation.

Prefrontal responses to digit span memory phases in patients with post-traumatic stress disorder (PTSD): a functional near infrared spectroscopy study.

PubMed

Tian, Fenghua; Yennu, Amarnath; Smith-Osborne, Alexa; Gonzalez-Lima, F; North, Carol S; Liu, Hanli

2014-01-01

Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related) forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.

Neural Correlates of Semantic Prediction and Resolution in Sentence Processing.

PubMed

Grisoni, Luigi; Miller, Tally McCormick; Pulvermüller, Friedemann

2017-05-03

Most brain-imaging studies of language comprehension focus on activity following meaningful stimuli. Testing adult human participants with high-density EEG, we show that, already before the presentation of a critical word, context-induced semantic predictions are reflected by a neurophysiological index, which we therefore call the semantic readiness potential (SRP). The SRP precedes critical words if a previous sentence context constrains the upcoming semantic content (high-constraint contexts), but not in unpredictable (low-constraint) contexts. Specific semantic predictions were indexed by SRP sources within the motor system-in dorsolateral hand motor areas for expected hand-related words (e.g., "write"), but in ventral motor cortex for face-related words ("talk"). Compared with affirmative sentences, negated ones led to medial prefrontal and more widespread motor source activation, the latter being consistent with predictive semantic computation of alternatives to the negated expected concept. Predictive processing of semantic alternatives in negated sentences is further supported by a negative-going event-related potential at ∼400 ms (N400), which showed the typical enhancement to semantically incongruent sentence endings only in high-constraint affirmative contexts, but not to high-constraint negated ones. These brain dynamics reveal the interplay between semantic prediction and resolution (match vs error) processing in sentence understanding. SIGNIFICANCE STATEMENT Most neuroscientists agree on the eminent importance of predictive mechanisms for understanding basic as well as higher brain functions. This contrasts with a sparseness of brain measures that directly reflects specific aspects of prediction, as they are relevant in the processing of language and thought. Here we show that when critical words are strongly expected in their sentence context, a predictive brain response reflects meaning features of these anticipated symbols already before they appear. The granularity of the semantic predictions was so fine grained that the cortical sources in sensorimotor and medial prefrontal cortex even distinguished between predicted face- or hand-related action words (e.g., the words "lick" or "pick") and between affirmative and negated sentence meanings. Copyright © 2017 Grisoni et al.

Neural Correlates of Semantic Prediction and Resolution in Sentence Processing

PubMed Central

2017-01-01

Most brain-imaging studies of language comprehension focus on activity following meaningful stimuli. Testing adult human participants with high-density EEG, we show that, already before the presentation of a critical word, context-induced semantic predictions are reflected by a neurophysiological index, which we therefore call the semantic readiness potential (SRP). The SRP precedes critical words if a previous sentence context constrains the upcoming semantic content (high-constraint contexts), but not in unpredictable (low-constraint) contexts. Specific semantic predictions were indexed by SRP sources within the motor system—in dorsolateral hand motor areas for expected hand-related words (e.g., “write”), but in ventral motor cortex for face-related words (“talk”). Compared with affirmative sentences, negated ones led to medial prefrontal and more widespread motor source activation, the latter being consistent with predictive semantic computation of alternatives to the negated expected concept. Predictive processing of semantic alternatives in negated sentences is further supported by a negative-going event-related potential at ∼400 ms (N400), which showed the typical enhancement to semantically incongruent sentence endings only in high-constraint affirmative contexts, but not to high-constraint negated ones. These brain dynamics reveal the interplay between semantic prediction and resolution (match vs error) processing in sentence understanding. SIGNIFICANCE STATEMENT Most neuroscientists agree on the eminent importance of predictive mechanisms for understanding basic as well as higher brain functions. This contrasts with a sparseness of brain measures that directly reflects specific aspects of prediction, as they are relevant in the processing of language and thought. Here we show that when critical words are strongly expected in their sentence context, a predictive brain response reflects meaning features of these anticipated symbols already before they appear. The granularity of the semantic predictions was so fine grained that the cortical sources in sensorimotor and medial prefrontal cortex even distinguished between predicted face- or hand-related action words (e.g., the words “lick” or “pick”) and between affirmative and negated sentence meanings. PMID:28411271

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

PubMed

Burrus, Caley

2013-11-01

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

Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.

PubMed

Negrón-Oyarzo, Ignacio; Espinosa, Nelson; Aguilar, Marcelo; Fuenzalida, Marco; Aboitiz, Francisco; Fuentealba, Pablo

2018-06-18

Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal-hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial.

PubMed

Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Hamada, Kasumi; Okuhata, Shiho; Kawasaki, Shingo; Kuwabara, Hitoshi; Shimada, Takafumi; Todokoro, Ayako; Igarashi, Takashi; Watanabe, Kei-Ichiro; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

2015-11-01

Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with attention-deficit hyperactivity disorder (ADHD), the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the Clinical Global Impressions-Severity (CGI-S) score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-to-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared with the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.

Tonic or Phasic Stimulation of Dopaminergic Projections to Prefrontal Cortex Causes Mice to Maintain or Deviate from Previously Learned Behavioral Strategies

PubMed Central

Ellwood, Ian T.; Patel, Tosha; Wadia, Varun; Lee, Anthony T.; Liptak, Alayna T.

2017-01-01

Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction errors and can drive reinforcement learning through their projections to striatum, but much less is known about their projections to prefrontal cortex (PFC). Here, we studied these projections and observed phasic VTA–PFC fiber photometry signals after the delivery of rewards. Next, we studied how optogenetic stimulation of these projections affects behavior using conditioned place preference and a task in which mice learn associations between cues and food rewards and then use those associations to make choices. Neither phasic nor tonic stimulation of dopaminergic VTA–PFC projections elicited place preference. Furthermore, substituting phasic VTA–PFC stimulation for food rewards was not sufficient to reinforce new cue–reward associations nor maintain previously learned ones. However, the same patterns of stimulation that failed to reinforce place preference or cue–reward associations were able to modify behavior in other ways. First, continuous tonic stimulation maintained previously learned cue–reward associations even after they ceased being valid. Second, delivering phasic stimulation either continuously or after choices not previously associated with reward induced mice to make choices that deviated from previously learned associations. In summary, despite the fact that dopaminergic VTA–PFC projections exhibit phasic increases in activity that are time locked to the delivery of rewards, phasic activation of these projections does not necessarily reinforce specific actions. Rather, dopaminergic VTA–PFC activity can control whether mice maintain or deviate from previously learned cue–reward associations. SIGNIFICANCE STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum encode reward prediction errors and reinforce specific actions; however, it is currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play similar or distinct roles. Here, we used bulk Ca2+ imaging to show that unexpected rewards or reward-predicting cues elicit phasic increases in the activity of dopaminergic VTA–PFC fibers. However, in multiple behavioral paradigms, we failed to observe reinforcing effects after stimulation of these fibers. In these same experiments, we did find that tonic or phasic patterns of stimulation caused mice to maintain or deviate from previously learned cue–reward associations, respectively. Therefore, although they may exhibit similar patterns of activity, dopaminergic inputs to striatum and PFC can elicit divergent behavioral effects. PMID:28739583

Enriched encoding: reward motivation organizes cortical networks for hippocampal detection of unexpected events.

PubMed

Murty, Vishnu P; Adcock, R Alison

2014-08-01

Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical-hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions-a potentially unique contribution of the hippocampus to reward learning. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Plasticity in the Rat Prefrontal Cortex: Linking Gene Expression and an Operant Learning with a Computational Theory

PubMed Central

Rapanelli, Maximiliano; Lew, Sergio Eduardo; Frick, Luciana Romina; Zanutto, Bonifacio Silvano

2010-01-01

The plasticity in the medial Prefrontal Cortex (mPFC) of rodents or lateral prefrontal cortex in non human primates (lPFC), plays a key role neural circuits involved in learning and memory. Several genes, like brain-derived neurotrophic factor (BDNF), cAMP response element binding (CREB), Synapsin I, Calcium/calmodulin-dependent protein kinase II (CamKII), activity-regulated cytoskeleton-associated protein (Arc), c-jun and c-fos have been related to plasticity processes. We analysed differential expression of related plasticity genes and immediate early genes in the mPFC of rats during learning an operant conditioning task. Incompletely and completely trained animals were studied because of the distinct events predicted by our computational model at different learning stages. During learning an operant conditioning task, we measured changes in the mRNA levels by Real-Time RT-PCR during learning; expression of these markers associated to plasticity was incremented while learning and such increments began to decline when the task was learned. The plasticity changes in the lPFC during learning predicted by the model matched up with those of the representative gene BDNF. Herein, we showed for the first time that plasticity in the mPFC in rats during learning of an operant conditioning is higher while learning than when the task is learned, using an integrative approach of a computational model and gene expression. PMID:20111591

The relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms.

PubMed

Balderston, Nicholas L; Liu, Jeffrey; Roberson-Nay, Roxann; Ernst, Monique; Grillon, Christian

2017-11-30

Panic disorder is characterized by sudden, repeated, and unexpected attacks of intense fear and overwhelming anxiety about when another attack may strike. Patients with panic disorder and healthy individuals with a history of panic attacks show a hypersensitivity to unpredictable threats, suggesting a possible link between panic and sustained anxiety. The purpose of this study was to determine the degree to which induced symptoms of panic relate to fear and anxiety, as well as activity in the neural systems that mediate and regulate these affective states. Psychological and physiological symptoms of panic were assessed during an 8-min 7.5% CO 2 challenge task. Psychological, physiological, and neural symptoms of fear and anxiety were measured during two sessions (one psychophysiology and one functional magnetic resonance imaging where subjects experienced several blocks of no threat (N), predictable shock (P), and unpredictable shock (U; NPU threat task). We used a principle component analysis to characterize panic susceptibility (PS), and found that PS significantly predicted dorsolateral prefrontal cortex (dlPFC) activity to the unpredictable cue during the NPU threat task. When examining the weighted beta coefficients from this analysis, we observed that self-reported fear/anxiety during the CO 2 challenge negatively loaded onto dlPFC activity during the NPU task. Consistent with this observation, dlPFC activity during the unpredictable cue was also negatively correlated with anxiety during the NPU sessions. Together, these results suggest that panic symptoms and anxiety are regulated by the same prefrontal cognitive control system.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2009-07-15

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

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

PubMed

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

2018-02-16

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

Raloxifene increases prefrontal activity during emotional inhibition in schizophrenia based on estrogen receptor genotype.

PubMed

Kindler, Jochen; Weickert, Cynthia Shannon; Schofield, Peter R; Lenroot, Rhoshel; Weickert, Thomas W

2016-12-01

People with schizophrenia show decreased prefrontal cortex (PFC) activity during emotional response inhibition, a cognitive process sensitive to hormonal influences. Raloxifene, a selective estrogen receptor modulator, binds estrogen receptor alpha (ESR-α), improves memory, attention and normalizes cortical and hippocampal activity during learning and emotional face recognition in schizophrenia. Here, we tested the extent to which raloxifene restores neuronal activity during emotional response inhibition in schizophrenia. Since genetic variation in estrogen receptor alpha (ESR-1) determines cortical ESR-α production and correlates with cognition, we also predicted that genetic ESR-1 variation would differentially relate to increased cortical activity by raloxifene administration. Thirty people with schizophrenia participated in a thirteen-week randomized, double-blind, placebo-controlled, cross-over adjunctive treatment trial of raloxifene administered at 120mg/day. Effects of raloxifene on brain activation were assessed based on ESR-1 genotype using functional magnetic resonance imaging during emotional word inhibition. Raloxifene increased PFC activity during inhibition of response to negative words and the raloxifene related increased PFC activity was greater in patients homozygous for ESR-1 rs9340799 AA relative to G carriers. Comparison to 23 healthy controls demonstrated that PFC activity of people with schizophrenia receiving raloxifene was more similar to controls than to their own brain activity during placebo. Estrogen receptor modulation by raloxifene restores PFC activity during emotional response inhibition in schizophrenia and ESR-1 genotype predicts degree of increased neural activity in response to raloxifene. While these preliminary results require replication, they suggest the potential for personalized pharmacotherapy using ESR-1 and estrogen receptor targeting compounds in schizophrenia. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

A longitudinal fMRI investigation in acute post-traumatic stress disorder (PTSD).

PubMed

Ke, Jun; Zhang, Li; Qi, Rongfeng; Li, Weihui; Hou, Cailan; Zhong, Yuan; He, Zhong; Li, Lingjiang; Lu, Guangming

2016-11-01

Background Neuroimaging studies have implicated limbic, paralimbic, and prefrontal cortex in the pathophysiology of chronic post-traumatic stress disorder (PTSD). However, little is known about the neural substrates of acute PTSD and how they change with symptom improvement. Purpose To examine the neural circuitry underlying acute PTSD and brain function changes during clinical recovery from this disorder. Material and Methods Nineteen acute PTSD patients and nine non-PTSD subjects who all experienced a devastating mining accident underwent clinical assessment as well as functional magnetic resonance imaging (fMRI) scanning while viewing trauma-related and neutral pictures. Two years after the accident, a subgroup of 17 patients completed a second clinical evaluation, of which 13 were given an identical follow-up scan. Results Acute PTSD patients demonstrated greater activation in the vermis and right posterior cingulate, and greater deactivation in the bilateral medial prefrontal cortex and inferior parietal lobules than controls in the traumatic versus neutral condition. At follow-up, PTSD patients showed symptom reduction and decreased activation in the right middle frontal gyrus, bilateral posterior cingulate/precuneus, and cerebellum. Correlation results confirmed these findings and indicated that brain activation in the posterior cingulate/precuneus and vermis was predictive of PTSD symptom improvement. Conclusion The findings support the involvement of the medial prefrontal cortex, inferior parietal lobule, posterior cingulate, and vermis in the pathogenesis of acute PTSD. Brain activation in the vermis and posterior cingulate/precuneus appears to be a biological marker of recovery potential from PTSD. Furthermore, decreased activation of the middle frontal gyrus, posterior cingulate/precuneus, and cerebellum may reflect symptom improvement.

Neuropsychological correlates of cognitive, emotional-affective and auto-activation apathy in Alzheimer's disease.

PubMed

Perri, Roberta; Turchetta, Chiara Stella; Caruso, Giulia; Fadda, Lucia; Caltagirone, Carlo; Carlesimo, Augusto Giovanni

2018-01-31

Apathy symptoms include different dimensions: cognitive (C), emotional-affective (E-Aff) and auto-activation; they have been related to dysfunctions of the dorsolateral, orbito-basal prefrontal cortex and the subcortical frontal connections to the basal ganglia, respectively. In Alzheimer's disease (AD), an association has been found between apathy severity and both executive deficits and atrophy of the dorso-lateral prefrontal cortex; however, it is not clear whether these associations concern only the cognitive aspects of apathy. Furthermore, whether there is an association in AD between E-aff apathy and theory of mind (ToM),the cognitive functions subsumed by the orbito-basal prefrontal cortex, has not been investigated. Aim of the study was to investigate the relationship between C, E-Aff and auto-activation apathy and performance on tasks investigating executive and ToM cognitive functions in AD. For this purpose, 20 AD patients with apathy and 20 matched controls were submitted to an executive and ToM neuropsychological assessment. Apathy was assessed with a weekly diary (ApD) created specifically to assist caregivers in quantifying the C, E-Aff and auto-activation symptomatology of apathy. Correlational analyses showed that AD patients' scores on the Modified Card Sorting Test (MCST) and Emotion Attribution tasks were correlated with most ApD scores. However, regression analyses showed that C diary scores were predicted by MCST performance, E-Aff diary scores by performance on the E-Attribution task and ApD scores measuring auto-activation apathy were predicted by both the MCST and the Emotion Attribution scores. These results confirm the co-occurrence of apathy and executive-function deficits in AD and suggest a specific association between AD patients' executive deficits and the cognitive component of apathy. Furthermore, they document, for the first time, an association between poor performance on tests assessing ToM abilities and the emotional-affective component of apathy in AD patients. Finally, these results are in line with the view that auto-activation apathy reflects the sum of emotional and cognitive processing deficits. Copyright © 2018 Elsevier Ltd. All rights reserved.

Can functional magnetic resonance imaging studies help with the optimization of health messaging for lifestyle behavior change? A systematic review.

PubMed

Whelan, Maxine E; Morgan, Paul S; Sherar, Lauren B; Orme, Mark W; Esliger, Dale W

2017-06-01

Unhealthy behaviors, including smoking, poor nutrition, excessive alcohol consumption, physical inactivity and sedentary lifestyles, are global risk factors for non-communicable diseases and premature death. Functional magnetic resonance imaging (fMRI) offers a unique approach to optimize health messages by examining how the brain responds to information relating to health. Our aim was to systematically review fMRI studies that have investigated variations in brain activation in response to health messages relating to (i) smoking; (ii) alcohol consumption; (iii) physical activity; (iv) diet; and (v) sedentary behavior. The electronic databases used were Medline/PubMed, Web of Science (Core Collection), PsychINFO, SPORTDiscuss, Cochrane Library and Open Grey. Studies were included if they investigated subjects aged ≥10years and were published before January 2017. Of the 13,836 studies identified in the database search, 18 studies (smoking k=15; diet k=2; physical activity/sedentary behavior k=1) were included in the review. The prefrontal cortex was activated in seven (47%) of the smoking-related studies and the physical activity study. Results suggest that activation of the ventromedial, dorsolateral and medial prefrontal cortex regions were predictive of subsequent behavior change following exposure to aversive anti-smoking stimuli. Studies investigating the neurological responses to anti-smoking material were most abundant. Of note, the prefrontal cortex and amygdala were most commonly activated in response to health messages across lifestyle behaviors. The review highlights an important disparity between research focusing on different lifestyle behaviors. Insights from smoking literature suggest fMRI may help to optimize health messaging in relation to other lifestyle behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val --> Met.

PubMed

Roffman, Joshua L; Gollub, Randy L; Calhoun, Vince D; Wassink, Thomas H; Weiss, Anthony P; Ho, Beng C; White, Tonya; Clark, Vincent P; Fries, Jill; Andreasen, Nancy C; Goff, Donald C; Manoach, Dara S

2008-11-11

Understanding how risk genes cumulatively impair brain function in schizophrenia could provide critical insights into its pathophysiology. Working memory impairment in schizophrenia has been associated with abnormal dopamine signaling in the prefrontal cortex, which is likely under complex genetic control. The catechol-O-methyltransferase (COMT) 158Val --> Met polymorphism (rs4680), which affects the availability of prefrontal dopamine signaling, consistently stratifies prefrontal activation during working memory performance. However, the low-dopamine COMT 158Val allele does not confer increased risk for schizophrenia, and its effects on prefrontal function are not specific to the disorder. In the setting of other genetic variants influencing prefrontal dopamine signaling, COMT 158Val --> Met genotype may exert disease-specific effects. A second polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C --> T (rs1801133), has been associated with overall schizophrenia risk and executive function impairment in patients, and may influence dopamine signaling through mechanisms upstream of COMT effects. We found that the hypofunctional 677T variant was associated with decreased working memory load-dependent activation in the prefrontal and insular cortices in 79 schizophrenia patients, but not in 75 demographically matched healthy controls. Further, significant MTHFR x COMT genotype interactions were observed, which differed by diagnostic group: Reduced prefrontal activation was associated with the 677T and 158Val alleles in patients, but with 677C/C and 158Met/Met genotype in controls. These findings are consistent with epistatic effects of the COMT and MTHFR polymorphisms on prefrontal dopamine signaling, and suggest that in schizophrenia patients, the MTHFR 677T allele exacerbates prefrontal dopamine deficiency. The findings also suggest the importance of weighing COMT effects on prefrontal function within the context of MTHFR genotype.

Fronto-Limbic Functioning in Children and Adolescents with and without Autism

ERIC Educational Resources Information Center

Loveland, Katherine A.; Bachevalier, Jocelyne; Pearson, Deborah A.; Lane, David M.

2008-01-01

We used neuropsychological tasks to investigate integrity of brain circuits linking orbitofrontal cortex and amygdala (orbitofrontal-amygdala), and dorsolateral prefrontal cortex and hippocampus (dorsolateral prefrontal-hippocampus), in 138 individuals aged 7-18 years, with and without autism. We predicted that performance on…

A Role for Prefrontal Calcium-Sensitive Protein Phosphatase and Kinase Activities in Working Memory

ERIC Educational Resources Information Center

Runyan, Jason D.; Moore, Anthony N.; Dash, Pramod K.

2005-01-01

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the…

Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

PubMed Central

Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

2014-01-01

Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

Limbic and prefrontal responses to facial emotion expressions in depersonalization.

PubMed

Lemche, Erwin; Surguladze, Simon A; Giampietro, Vincent P; Anilkumar, Ananthapadmanabha; Brammer, Michael J; Sierra, Mauricio; Chitnis, Xavier; Williams, Steven C R; Gasston, David; Joraschky, Peter; David, Anthony S; Phillips, Mary L

2007-03-26

Depersonalization disorder, characterized by emotional detachment, has been associated with increased prefrontal cortical and decreased autonomic activity to emotional stimuli. Event-related fMRI with simultaneous measurements of skin conductance levels occurred in nine depersonalization disorder patients and 12 normal controls to neutral, mild and intense happy and sad facial expressions. Patients, but not controls, showed decreases in subcortical limbic activity to increasingly intense happy and sad facial expressions, respectively. For both happy and sad expressions, negative correlations between skin conductance measures in bilateral dorsal prefrontal cortices occurred only in depersonalization disorder patients. Abnormal decreases in limbic activity to increasingly intense emotional expressions, and increases in dorsal prefrontal cortical activity to emotionally arousing stimuli may underlie the emotional detachment of depersonalization disorder.

Separate encoding of model-based and model-free valuations in the human brain.

PubMed

Beierholm, Ulrik R; Anen, Cedric; Quartz, Steven; Bossaerts, Peter

2011-10-01

Behavioral studies have long shown that humans solve problems in two ways, one intuitive and fast (System 1, model-free), and the other reflective and slow (System 2, model-based). The neurobiological basis of dual process problem solving remains unknown due to challenges of separating activation in concurrent systems. We present a novel neuroeconomic task that predicts distinct subjective valuation and updating signals corresponding to these two systems. We found two concurrent value signals in human prefrontal cortex: a System 1 model-free reinforcement signal and a System 2 model-based Bayesian signal. We also found a System 1 updating signal in striatal areas and a System 2 updating signal in lateral prefrontal cortex. Further, signals in prefrontal cortex preceded choices that are optimal according to either updating principle, while signals in anterior cingulate cortex and globus pallidus preceded deviations from optimal choice for reinforcement learning. These deviations tended to occur when uncertainty regarding optimal values was highest, suggesting that disagreement between dual systems is mediated by uncertainty rather than conflict, confirming recent theoretical proposals. Copyright © 2011 Elsevier Inc. All rights reserved.

Pharmacogenetic excitation of dorsomedial prefrontal cortex restores fear prediction error.

PubMed

Yau, Joanna Oi-Yue; McNally, Gavan P

2015-01-07

Pavlovian conditioning involves encoding the predictive relationship between a conditioned stimulus (CS) and an unconditioned stimulus, so that synaptic plasticity and learning is instructed by prediction error. Here we used pharmacogenetic techniques to show a causal relation between activity of rat dorsomedial prefrontal cortex (dmPFC) neurons and fear prediction error. We expressed the excitatory hM3Dq designer receptor exclusively activated by a designer drug (DREADD) in dmPFC and isolated actions of prediction error by using an associative blocking design. Rats were trained to fear the visual CS (CSA) in stage I via pairings with footshock. Then in stage II, rats received compound presentations of visual CSA and auditory CS (CSB) with footshock. This prior fear conditioning of CSA reduced the prediction error during stage II to block fear learning to CSB. The group of rats that received AAV-hSYN-eYFP vector that was treated with clozapine-N-oxide (CNO; 3 mg/kg, i.p.) before stage II showed blocking when tested in the absence of CNO the next day. In contrast, the groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIα-hM3Dq that were treated with CNO before stage II training did not show blocking; learning toward CSB was restored. This restoration of prediction error and fear learning was specific to the injection of CNO because groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIα-hM3Dq that were injected with vehicle before stage II training did show blocking. These effects were not attributable to the DREADD manipulation enhancing learning or arousal, increasing fear memory strength or asymptotic levels of fear learning, or altering fear memory retrieval. Together, these results identify a causal role for dmPFC in a signature of adaptive behavior: using the past to predict future danger and learning from errors in these predictions. Copyright © 2015 the authors 0270-6474/15/350074-10$15.00/0.

Neural predictors of purchases

PubMed Central

Knutson, Brian; Rick, Scott; Wimmer, G. Elliott; Prelec, Drazen; Loewenstein, George

2007-01-01

Microeconomic theory maintains that purchases are driven by a combination of consumer preference and price. Using event-related FMRI, we investigated how people weigh these factors to make purchasing decisions. Consistent with neuroimaging evidence suggesting that distinct circuits anticipate gain and loss, product preference activated the nucleus accumbens (NAcc), while excessive prices activated the insula and deactivated the mesial prefrontal cortex (MPFC) prior to the purchase decision. Activity from each of these regions independently predicted immediately subsequent purchases above and beyond self-report variables. These findings suggest that activation of distinct neural circuits related to anticipatory affect precedes and supports consumers’ purchasing decisions. PMID:17196537

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

PubMed

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

2016-11-01

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

Self-affirmation activates brain systems associated with self-related processing and reward and is reinforced by future orientation

PubMed Central

O’Donnell, Matthew Brook; Tinney, Francis J.; Lieberman, Matthew D.; Taylor, Shelley E.; Strecher, Victor J.; Falk, Emily B.

2016-01-01

Self-affirmation theory posits that people are motivated to maintain a positive self-view and that threats to perceived self-competence are met with resistance. When threatened, self-affirmations can restore self-competence by allowing individuals to reflect on sources of self-worth, such as core values. Many questions exist, however, about the underlying mechanisms associated with self-affirmation. We examined the neural mechanisms of self-affirmation with a task developed for use in a functional magnetic resonance imaging environment. Results of a region of interest analysis demonstrated that participants who were affirmed (compared with unaffirmed participants) showed increased activity in key regions of the brain’s self-processing (medial prefrontal cortex + posterior cingulate cortex) and valuation (ventral striatum + ventral medial prefrontal cortex) systems when reflecting on future-oriented core values (compared with everyday activities). Furthermore, this neural activity went on to predict changes in sedentary behavior consistent with successful affirmation in response to a separate physical activity intervention. These results highlight neural processes associated with successful self-affirmation, and further suggest that key pathways may be amplified in conjunction with prospection. PMID:26541373

Disrupted neural processing of emotional faces in psychopathy.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Bosque, Javier; Ibern-Regàs, Immaculada; Hernández-Ribas, Rosa; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2014-04-01

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths' affective-interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.

The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory

PubMed Central

Hales, J. B.

2011-01-01

The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance. PMID:21248058

COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

PubMed

Miller, Shefali; McTeague, Lisa M; Gyurak, Anett; Patenaude, Brian; Williams, Leanne M; Grieve, Stuart M; Korgaonkar, Mayuresh S; Etkin, Amit

2015-08-01

Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients. Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes. Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment. The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes. © 2015 Wiley Periodicals, Inc.

Functional connectivity of default mode network components: correlation, anticorrelation, and causality

PubMed Central

Uddin, Lucina Q.; Clare Kelly, A. M.; Biswal, Bharat B.; Castellanos, F. Xavier; Milham, Michael P.

2013-01-01

The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), exhibits higher metabolic activity at rest than during performance of externally-oriented cognitive tasks. Recent studies have suggested that competitive relationships between the DMN and various task-positive networks involved in task performance are intrinsically represented in the brain in the form of strong negative correlations (anticorrelations) between spontaneous fluctuations in these networks. Most neuroimaging studies characterize the DMN as a homogenous network, thus few have examined the differential contributions of DMN components to such competitive relationships. Here we examined functional differentiation within the default mode network, with an emphasis on understanding competitive relationships between this and other networks. We used a seed correlation approach on resting-state data to assess differences in functional connectivity between these two regions and their anticorrelated networks. While the positively correlated networks for the vmPFC and PCC seeds largely overlapped, the anticorrelated networks for each showed striking differences. Activity in vmPFC negatively predicted activity in parietal visual spatial and temporal attention networks, whereas activity in PCC negatively predicted activity in prefrontal-based motor control circuits. Granger causality analyses suggest that vmPFC and PCC exert greater influence on their anticorrelated networks than the other way around, suggesting that these two default mode nodes may directly modulate activity in task-positive networks. Thus, the two major nodes comprising the default mode network are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated. PMID:18219617

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

PubMed

Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

Developmental frontal lobe imaging in moral judgment: Arthur Benton's enduring influence 60 years later.

PubMed

Eslinger, Paul J; Robinson-Long, Melissa; Realmuto, Jennifer; Moll, Jorge; deOliveira-Souza, Ricardo; Tovar-Moll, Fernanda; Wang, Jianli; Yang, Qing X

2009-02-01

Early prefrontal cortex damage has been associated with developmental deficits in social adaptation, moral behavior, and empathy that alter the maturation of social cognition and social emotions. The seminal case of Ackerly and Benton (1948) continues to provide the most striking clinical example of prefrontal-related neurodevelopmental impairments, with more recent case reports confirming and elaborating these influential observations. This study investigated the prefrontal hypothesis of moral decision making in healthy, typically developing children and adolescents (10-17 years of age) using functional magnetic resonance imaging (fMRI). Participants judged the actions in age-appropriate moral vignettes as right or wrong, and results were contrasted to a nonsocial/nonmoral baseline condition requiring similar right versus wrong judgments. Results confirmed a predominant cluster of activity in the most rostral-medial (frontal polar) prefrontal region across moral judgment conditions, along with left lateroposterior orbitofrontal/ventrolateral prefrontal, left temporoparietal junction, midline thalamus and globus pallidus, and bilateral inferior occipital clusters. Trials entailing ambiguous moral situations activated considerably more prefrontal and parietal regions than did routine moral situations, suggesting the need for more neurocognitive resources. While age regression analysis identified a few regions of greater or lesser activity with age, the frontal polar activations did not change with age. Findings confirm a significant role for anterior-medial prefrontal cortex in the typical development and maturation of moral decision making, consistent with clinical lesion case descriptions.

Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control.

PubMed

Christakou, Anastasia; Halari, Rozmin; Smith, Anna B; Ifkovits, Eve; Brammer, Mick; Rubia, Katya

2009-10-15

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

Prefrontal cortex activity during swallowing in dysphagia patients.

PubMed

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

2018-05-24

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

The Conforming Brain and Deontological Resolve

PubMed Central

Pincus, Melanie; LaViers, Lisa; Prietula, Michael J.; Berns, Gregory

2014-01-01

Our personal values are subject to forces of social influence. Deontological resolve captures how strongly one relies on absolute rules of right and wrong in the representation of one's personal values and may predict willingness to modify one's values in the presence of social influence. Using fMRI, we found that a neurobiological metric for deontological resolve based on relative activity in the ventrolateral prefrontal cortex (VLPFC) during the passive processing of sacred values predicted individual differences in conformity. Individuals with stronger deontological resolve, as measured by greater VLPFC activity, displayed lower levels of conformity. We also tested whether responsiveness to social reward, as measured by ventral striatal activity during social feedback, predicted variability in conformist behavior across individuals but found no significant relationship. From these results we conclude that unwillingness to conform to others' values is associated with a strong neurobiological representation of social rules. PMID:25170989

A face to remember: emotional expression modulates prefrontal activity during memory formation.

PubMed

Sergerie, Karine; Lepage, Martin; Armony, Jorge L

2005-01-15

Emotion can exert a modulatory role on episodic memory. Several studies have shown that negative stimuli (e.g., words, pictures) are better remembered than neutral ones. Although facial expressions are powerful emotional stimuli and have been shown to influence perception and attention processes, little is known about their effect on memory. We used functional magnetic resonance imaging (fMRI) in humans to investigate the effects of expression (happy, neutral, and fearful) on prefrontal cortex (PFC) activity during the encoding of faces, using a subsequent memory effect paradigm. Our results show that activity in right PFC predicted memory for faces, regardless of expression, while a homotopic region in the left hemisphere was associated with successful encoding only for faces with an emotional expression. These findings are consistent with the proposed role of right dorsolateral PFC in successful encoding of nonverbal material, but also suggest that left DLPFC may be a site where integration of memory and emotional processes occurs. This study sheds new light on the current controversy regarding the hemispheric lateralization of PFC in memory encoding.

The link between social cognition and self-referential thought in the medial prefrontal cortex.

PubMed

Mitchell, Jason P; Banaji, Mahzarin R; Macrae, C Neil

2005-08-01

The medial prefrontal cortex (mPFC) has been implicated in seemingly disparate cognitive functions, such as understanding the minds of other people and processing information about the self. This functional overlap would be expected if humans use their own experiences to infer the mental states of others, a basic postulate of simulation theory. Neural activity was measured while participants attended to either the mental or physical aspects of a series of other people. To permit a test of simulation theory's prediction that inferences based on self-reflection should only be made for similar others, targets were subsequently rated for their degree of similarity to self. Parametric analyses revealed a region of the ventral mPFC--previously implicated in self-referencing tasks--in which activity correlated with perceived self/other similarity, but only for mentalizing trials. These results suggest that self-reflection may be used to infer the mental states of others when they are sufficiently similar to self.

Prefrontal Parvalbumin Neurons in Control of Attention

PubMed Central

Kim, Hoseok; Ährlund-Richter, Sofie; Wang, Xinming; Deisseroth, Karl; Carlén, Marie

2016-01-01

Summary While signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control of attention are largely unknown. Using chronic recordings in mice, we found that fast-spiking parvalbumin (FS-PV) interneurons in medial prefrontal cortex (mPFC) uniformly show increased and sustained firing during goal-driven attentional processing, correlating to the level of attention. Elevated activity of FS-PV neurons on the timescale of seconds predicted successful execution of behavior. Successful allocation of attention was characterized by strong synchronization of FS-PV neurons, increased gamma oscillations, and phase locking of pyramidal firing. Phase-locked pyramidal neurons showed gamma-phase-dependent rate modulation during successful attentional processing. Optogenetic silencing of FS-PV neurons deteriorated attentional processing, while optogenetic synchronization of FS-PV neurons at gamma frequencies had pro-cognitive effects and improved goal-directed behavior. FS-PV neurons thus act as a functional unit coordinating the activity in the local mPFC circuit during goal-driven attentional processing. PMID:26771492

Neural correlates of reinforcement learning and social preferences in competitive bidding.

PubMed

van den Bos, Wouter; Talwar, Arjun; McClure, Samuel M

2013-01-30

In competitive social environments, people often deviate from what rational choice theory prescribes, resulting in losses or suboptimal monetary gains. We investigate how competition affects learning and decision-making in a common value auction task. During the experiment, groups of five human participants were simultaneously scanned using MRI while playing the auction task. We first demonstrate that bidding is well characterized by reinforcement learning with biased reward representations dependent on social preferences. Indicative of reinforcement learning, we found that estimated trial-by-trial prediction errors correlated with activity in the striatum and ventromedial prefrontal cortex. Additionally, we found that individual differences in social preferences were related to activity in the temporal-parietal junction and anterior insula. Connectivity analyses suggest that monetary and social value signals are integrated in the ventromedial prefrontal cortex and striatum. Based on these results, we argue for a novel mechanistic account for the integration of reinforcement history and social preferences in competitive decision-making.

Ventromedial prefrontal cortex generates pre-stimulus theta coherence desynchronization: A schema instantiation hypothesis.

PubMed

Gilboa, Asaf; Moscovitch, Morris

2017-02-01

The ventral medial prefrontal cortex (vmPFC) has long been implicated in monitoring of memory veracity, and more recently also in memory schema functions. In our model of strategic retrieval the two are related. We have proposed that the vmPFC has two schema-dependent functions: (i) to establish context-relevant templates against which the output of memory systems can be compared; (ii) to mediate automatic decision monitoring processes to ensure that only those responses that meet the criterion are enacted. Electroencephalogram (EEG) data were used to provide evidence that vmPFC supports both functions, and that schema instantiation informs monitoring. Participants viewed pictures of acquaintances, along with those of famous and nonfamous people, and were asked to respond positively only to pictures of individuals they had met (personal familiarity). The Self serves as a super-ordinate cognitive schema, facilitating accurate endorsement of acquaintances and exclusion of non-personal but familiar faces. For the present report we focused on pre-cue tonic oscillatory activity. Controls demonstrated theta coherence desynchronization between medial prefrontal areas, inferotemporal and lateral temporal cortices. These oscillatory coherence patterns were significantly reduced in patients with vmPFC damage, especially in those with clinical histories of spontaneous confabulation. Importantly, these pre-stimulus cortico-cortical desynchronizations predicted post-cue automatic memory activation, as indexed by a familiarity modulation of the face-sensitive posterior cortical N170. Pre-cue desynchronization also predicted early post-cue frontal positive modulation (P230) and response accuracy. The data are consistent with a schema instantiation model that suggests the vmPFC biases posterior neocortical long-term memory representations that enhance automatic memory cue processing and informs frontally-mediated rapid memory monitoring (P230). Damage to these structures can lead to inaccurate, context-irrelevant activation of schemas. These, in turn, impair monitoring signals and can lead to confabulation when memory control processes are also deficient. Copyright © 2016 Elsevier Ltd. All rights reserved.

An insula-frontostriatal network mediates flexible cognitive control by adaptively predicting changing control demands

PubMed Central

Jiang, Jiefeng; Beck, Jeffrey; Heller, Katherine; Egner, Tobias

2015-01-01

The anterior cingulate and lateral prefrontal cortices have been implicated in implementing context-appropriate attentional control, but the learning mechanisms underlying our ability to flexibly adapt the control settings to changing environments remain poorly understood. Here we show that human adjustments to varying control demands are captured by a reinforcement learner with a flexible, volatility-driven learning rate. Using model-based functional magnetic resonance imaging, we demonstrate that volatility of control demand is estimated by the anterior insula, which in turn optimizes the prediction of forthcoming demand in the caudate nucleus. The caudate's prediction of control demand subsequently guides the implementation of proactive and reactive attentional control in dorsal anterior cingulate and dorsolateral prefrontal cortices. These data enhance our understanding of the neuro-computational mechanisms of adaptive behaviour by connecting the classic cingulate-prefrontal cognitive control network to a subcortical control-learning mechanism that infers future demands by flexibly integrating remote and recent past experiences. PMID:26391305

Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: Converging electrochemical and fMRI evidence from rats and humans

PubMed Central

Howe, William M.; Berry, Anne S.; Francois, Jennifer; Gilmour, Gary; Carp, Joshua M.; Tricklebank, Mark; Lustig, Cindy; Sarter, Martin

2013-01-01

We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex during specific trial sequences in rats performing a task requiring signal detection as well as rejection of non-signal events. Cholinergic release events recorded with sub-second resolution (“transients”) were observed only during signal-hit trials, not during signal-miss trials or non-signal events. Moreover, cholinergic transients were not observed for consecutive hits; instead they were limited to signal-hit trials that were preceded by factual or perceived non-signal events (“incongruent hits”). This finding suggests that these transients mediate shifts from a state of perceptual attention, or monitoring for cues, to cue-evoked activation of response rules and the generation of a cue-directed response. Next, to determine the translational significance of the cognitive operations supporting incongruent hits we employed a version of the task previously validated for use in research in humans and BOLD-fMRI. Incongruent hits activated a region in the right rostral prefrontal cortex (BA 10). Furthermore, greater prefrontal activation was correlated with faster response times for incongruent hits. Finally, we measured tissue oxygen in rats, as a proxy for BOLD, and found prefrontal increases in oxygen levels solely during incongruent hits. These cross-species studies link a cholinergic response to a prefrontal BOLD activation and indicate that these interrelated mechanisms mediate the integration of external cues with internal representations to initiate and guide behavior. PMID:23678117

Decreasing Ventromedial Prefrontal Cortex Activity During Sequential Risk-Taking: An fMRI Investigation of the Balloon Analog Risk Task

PubMed Central

Schonberg, Tom; Fox, Craig R.; Mumford, Jeanette A.; Congdon, Eliza; Trepel, Christopher; Poldrack, Russell A.

2012-01-01

Functional imaging studies examining the neural correlates of risk have mainly relied on paradigms involving exposure to simple chance gambles and an economic definition of risk as variance in the probability distribution over possible outcomes. However, there is little evidence that choices made during gambling tasks predict naturalistic risk-taking behaviors such as drug use, extreme sports, or even equity investing. To better understand the neural basis of naturalistic risk-taking, we scanned participants using fMRI while they completed the Balloon Analog Risk Task, an experimental measure that includes an active decision/choice component and that has been found to correlate with a number of naturalistic risk-taking behaviors. In the task, as in many naturalistic settings, escalating risk-taking occurs under uncertainty and might be experienced either as the accumulation of greater potential rewards, or as exposure to increasing possible losses (and decreasing expected value). We found that areas previously linked to risk and risk-taking (bilateral anterior insula, anterior cingulate cortex, and right dorsolateral prefrontal cortex) were activated as participants continued to inflate balloons. Interestingly, we found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons. In light of previous findings implicating the vmPFC in value calculation, this result suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses (and decreasing expected value) rather than the increasing potential total reward relative to the starting point of the trial. A better understanding of how neural activity changes with risk-taking behavior in the task offers insight into the potential neural mechanisms driving naturalistic risk-taking. PMID:22675289

The roles of prefrontal and posterior parietal cortex in algebra problem solving: a case of using cognitive modeling to inform neuroimaging data.

PubMed

Danker, Jared F; Anderson, John R

2007-04-15

In naturalistic algebra problem solving, the cognitive processes of representation and retrieval are typically confounded, in that transformations of the equations typically require retrieval of mathematical facts. Previous work using cognitive modeling has associated activity in the prefrontal cortex with the retrieval demands of algebra problems and activity in the posterior parietal cortex with the transformational demands of algebra problems, but these regions tend to behave similarly in response to task manipulations (Anderson, J.R., Qin, Y., Sohn, M.-H., Stenger, V.A., Carter, C.S., 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261; Qin, Y., Carter, C.S., Silk, E.M., Stenger, A., Fissell, K., Goode, A., Anderson, J.R., 2004. The change of brain activation patterns as children learn algebra equation solving. Proc. Natl. Acad. Sci. 101, 5686-5691). With this study we attempt to isolate activity in these two regions by using a multi-step algebra task in which transformation (parietal) is manipulated in the first step and retrieval (prefrontal) is manipulated in the second step. Counter to our initial predictions, both brain regions were differentially active during both steps. We designed two cognitive models, one encompassing our initial assumptions and one in which both processes were engaged during both steps. The first model provided a poor fit to the behavioral and neural data, while the second model fit both well. This simultaneously emphasizes the strong relationship between retrieval and representation in mathematical reasoning and demonstrates that cognitive modeling can serve as a useful tool for understanding task manipulations in neuroimaging experiments.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder.

PubMed

Hassel, Stefanie; Almeida, Jorge R; Frank, Ellen; Versace, Amelia; Nau, Sharon A; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2009-11-01

The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Small sample size of predominantly medicated BD individuals. This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

With you or against you: social orientation dependent learning signals guide actions made for others.

PubMed

Christopoulos, George I; King-Casas, Brooks

2015-01-01

In social environments, it is crucial that decision-makers take account of the impact of their actions not only for oneself, but also on other social agents. Previous work has identified neural signals in the striatum encoding value-based prediction errors for outcomes to oneself; also, recent work suggests that neural activity in prefrontal cortex may similarly encode value-based prediction errors related to outcomes to others. However, prior work also indicates that social valuations are not isomorphic, with social value orientations of decision-makers ranging on a cooperative to competitive continuum; this variation has not been examined within social learning environments. Here, we combine a computational model of learning with functional neuroimaging to examine how individual differences in orientation impact neural mechanisms underlying 'other-value' learning. Across four experimental conditions, reinforcement learning signals for other-value were identified in medial prefrontal cortex, and were distinct from self-value learning signals identified in striatum. Critically, the magnitude and direction of the other-value learning signal depended strongly on an individual's cooperative or competitive orientation toward others. These data indicate that social decisions are guided by a social orientation-dependent learning system that is computationally similar but anatomically distinct from self-value learning. The sensitivity of the medial prefrontal learning signal to social preferences suggests a mechanism linking such preferences to biases in social actions and highlights the importance of incorporating heterogeneous social predispositions in neurocomputational models of social behavior. Published by Elsevier Inc.

With you or against you: Social orientation dependent learning signals guide actions made for others

PubMed Central

Christopoulos, George I.; King-Casas, Brooks

2014-01-01

In social environments, it is crucial that decision-makers take account of the impact of their actions not only for oneself, but also on other social agents. Previous work has identified neural signals in the striatum encoding value-based prediction errors for outcomes to oneself; also, recent work suggests neural activity in prefrontal cortex may similarly encode value-based prediction errors related to outcomes to others. However, prior work also indicates that social valuations are not isomorphic, with social value orientations of decision-makers ranging on a cooperative to competitive continuum; this variation has not been examined within social learning environments. Here, we combine a computational model of learning with functional neuroimaging to examine how individual differences in orientation impact neural mechanisms underlying ‘other-value’ learning. Across four experimental conditions, reinforcement learning signals for other-value were identified in medial prefrontal cortex, and were distinct from self-value learning signals identified in striatum. Critically, the magnitude and direction of the other-value learning signal depended strongly on an individual’s cooperative or competitive orientation towards others. These data indicate that social decisions are guided by a social orientation-dependent learning system that is computationally similar but anatomically distinct from self-value learning. The sensitivity of the medial prefrontal learning signal to social preferences suggests a mechanism linking such preferences to biases in social actions and highlights the importance of incorporating heterogeneous social predispositions in neurocomputational models of social behavior. PMID:25224998

Changes in Frontal EEG Coherence across Infancy Predict Cognitive Abilities at Age 3: The Mediating Role of Attentional Control

ERIC Educational Resources Information Center

Whedon, Margaret; Perry, Nicole B.; Calkins, Susan D.; Bell, Martha Ann

2016-01-01

Theoretical perspectives of cognitive development have maintained that functional integration of the prefrontal cortex across infancy underlies the emergence of attentional control and higher cognitive abilities in early childhood. To investigate these proposed relations, we tested whether functional integration of prefrontal regions across the…

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…

Associations between Children's Socioeconomic Status and Prefrontal Cortical Thickness

ERIC Educational Resources Information Center

Lawson, Gwendolyn M.; Duda, Jeffrey T.; Avants, Brian B.; Wu, Jue; Farah, Martha J.

2013-01-01

Childhood socioeconomic status (SES) predicts executive function performance and measures of prefrontal cortical function, but little is known about its anatomical correlates. Structural MRI and demographic data from a sample of 283 healthy children from the NIH MRI Study of Normal Brain Development were used to investigate the relationship…

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

PubMed

Philip, Noah S; Barredo, Jennifer; van 't Wout-Frank, Mascha; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

2018-02-01

Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders. Published by Elsevier Inc.

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

PubMed

Lepage, Martin

2004-03-01

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

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

PubMed

Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

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.

Prefrontal activity and diagnostic monitoring of memory retrieval: FMRI of the criterial recollection task.

PubMed

Gallo, David A; Kensinger, Elizabeth A; Schacter, Daniel L

2006-01-01

According to the distinctiveness heuristic, subjects rely more on detailed recollections (and less on familiarity) when memory is tested for pictures relative to words, leading to reduced false recognition. If so, then neural regions that have been implicated in effortful postretrieval monitoring (e.g., dorsolateral prefrontal cortex) might be recruited less heavily when trying to remember pictures. We tested this prediction with the criterial recollection task. Subjects studied black words, paired with either the same word in red font or a corresponding colored picture. Red words were repeated at study to equate recognition hits for red words and pictures. During fMRI scanning, alternating red word memory tests and picture memory tests were given, using only white words as test stimuli (say "yes" only if you recollect a corresponding red word or picture, respectively). These tests were designed so that subjects had to rely on memory for the criterial information. Replicating prior behavioral work, we found enhanced rejection of lures on the picture test compared to the red word test, indicating that subjects had used a distinctiveness heuristic. Critically, dorsolateral prefrontal activity was reduced when rejecting familiar lures on the picture test, relative to the red word test. These findings indicate that reducing false recognition via the distinctiveness heuristic is not heavily dependent on frontally mediated postretrieval monitoring processes.

Prefrontal Asymmetry and Parent-Rated Temperament in Infants

PubMed Central

LoBue, Vanessa; Coan, James A.; Thrasher, Cat; DeLoache, Judy S.

2011-01-01

Indicators of temperament appear early in infancy and remain relatively stable over time. Despite a great deal of interest in biological indices of temperament, most studies of infant temperament rely on parental reports or behavioral tasks. Thus, the extent to which commonly used temperament measures relate to potential biological indicators of infant temperament is still relatively unknown. The current experiment examines the relationship between a common parental report measure of temperament – the Infant Behavior Questionnaire – Revised (IBQ-R) – and measures of frontal EEG asymmetry in infants. We examined associations between the subscales of the IBQ-R and frontal EEG asymmetry scores recorded during a combined series of neutral attentional and putatively emotional recording conditions in infants between 7 and 9 months of age. We predicted that approach-related subscales of the IBQ-R (e.g., Approach, Soothability) would be related to greater left prefrontal asymmetry, while withdrawal-related subscales (e.g., Distress to Limitations, Fear, Falling Reactivity, Perceptual Sensitivity) would be related to greater right prefrontal asymmetry. In the mid- and lateral-frontal regions, Approach, Distress to Limitations, Fear, Soothability, and Perceptual Sensitivity were generally associated with greater left frontal activation (rs≥.23, ps<0.05), while only Falling Reactivity was associated with greater right frontal activation (rs≤−.44, ps<0.05). Results suggest that variability in frontal EEG asymmetry is robustly associated with parental report measures of temperament in infancy. PMID:21829482

How Do Negative Emotions Impair Self-Control? A Neural Model of Negative Urgency

PubMed Central

Chester, David S.; Lynam, Donald R.; Milich, Richard; Powell, David K.; Andersen, Anders H.; DeWall, C. Nathan

2016-01-01

Self-control often fails when people experience negative emotions. Negative urgency represents the dispositional tendency to experience such self-control failure in response to negative affect. The neural underpinnings of negative urgency are not fully understood, nor is the more general phenomenon of self-control failure in response to negative emotions. Previous theorizing suggests that an insufficient, inhibitory response from the prefrontal cortex may be the culprit behind such self-control failure. However, we entertained an alternative hypothesis: negative emotions lead to self-control failure because they excessively tax inhibitory regions of the prefrontal cortex. Using fMRI, we compared the neural activity of people high in negative urgency with controls on an emotional, inhibitory Go/No-Go task. While experiencing negative (but not positive or neutral) emotions, participants high in negative urgency showed greater recruitment of inhibitory brain regions than controls. Suggesting a compensatory function, inhibitory accuracy among participants high in negative urgency was associated with greater prefrontal recruitment. Greater activity in the anterior insula on negatively-valenced, inhibitory trials predicted greater substance abuse one month and one year after the MRI scan among individuals high in negative urgency. These results suggest that, among people whose negative emotions often lead to self-control failure, excessive reactivity of the brain’s regulatory resources may be the culprit. PMID:26892861

Representation of aversive prediction errors in the human periaqueductal gray

PubMed Central

Roy, Mathieu; Shohamy, Daphna; Daw, Nathaniel; Jepma, Marieke; Wimmer, Elliott; Wager, Tor D.

2014-01-01

Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), an important structure for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value-related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate, and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics. PMID:25282614

Choice from non-choice: Predicting consumer preferences from BOLD signals obtained during passive viewing

PubMed Central

Levy, Ifat; Lazzaro, Stephanie C.; Rutledge, Robb B.; Glimcher, Paul W.

2011-01-01

Decision-making is often viewed as a two-stage process, where subjective values are first assigned to each option and then the option of the highest value is selected. Converging evidence suggests that these subjective values are represented in the striatum and medial prefrontal cortex (MPFC). A separate line of evidence suggests that activation in the same areas represents the values of rewards even when choice is not required, as in classical conditioning tasks. However, it is unclear whether the same neural mechanism is engaged in both cases. To address this question we measured brain activation with fMRI while human subjects passively viewed individual consumer goods. We then sampled activation from predefined regions of interest and used it to predict subsequent choices between the same items made outside of the scanner. Our results show that activation in the striatum and MPFC in the absence of choice predicts subsequent choices, suggesting that these brain areas represent value in a similar manner whether or not choice is required. PMID:21209196

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

PubMed Central

Pergolizzi, Denise; Chua, Elizabeth F.

2016-01-01

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

The change of the brain activation patterns as children learn algebra equation solving

NASA Astrophysics Data System (ADS)

Qin, Yulin; Carter, Cameron S.; Silk, Eli M.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Anderson, John R.

2004-04-01

In a brain imaging study of children learning algebra, it is shown that the same regions are active in children solving equations as are active in experienced adults solving equations. As with adults, practice in symbol manipulation produces a reduced activation in prefrontal cortex area. However, unlike adults, practice seems also to produce a decrease in a parietal area that is holding an image of the equation. This finding suggests that adolescents' brain responses are more plastic and change more with practice. These results are integrated in a cognitive model that predicts both the behavioral and brain imaging results.

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

PubMed

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

2012-01-16

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

Dissociable prefrontal brain systems for attention and emotion

NASA Astrophysics Data System (ADS)

Yamasaki, Hiroshi; Labar, Kevin S.; McCarthy, Gregory

2002-08-01

The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders. novelty | prefrontal cortex | amygdala | cingulate gyrus

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

PubMed

Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

2008-07-16

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

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

PubMed

Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Kuwabara, Hitoshi; Matsubayashi, Junko; Hamada, Kasumi; Okuhata, Shiho; Yahata, Noriaki; Igarashi, Takashi; Kawasaki, Shingo; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

2014-01-01

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

Predicting Persuasion-Induced Behavior Change from the Brain

PubMed Central

Falk, Emily B.; Berkman, Elliot T.; Mann, Traci; Harrison, Brittany; Lieberman, Matthew D.

2011-01-01

Although persuasive messages often alter people’s self-reported attitudes and intentions to perform behaviors, these self-reports do not necessarily predict behavior change. We demonstrate that neural responses to persuasive messages can predict variability in behavior change in the subsequent week. Specifically, an a priori region of interest (ROI) in medial prefrontal cortex (MPFC) was reliably associated with behavior change (r = 0.49, p < 0.05). Additionally, an iterative cross-validation approach using activity in this MPFC ROI predicted an average 23% of the variance in behavior change beyond the variance predicted by self-reported attitudes and intentions. Thus, neural signals can predict behavioral changes that are not predicted from self-reported attitudes and intentions alone. Additionally, this is the first functional magnetic resonance imaging study to demonstrate that a neural signal can predict complex real world behavior days in advance. PMID:20573889

Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

PubMed

Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

2015-12-01

Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism

PubMed Central

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus. PMID:26244675

Functional brain imaging predicts public health campaign success

PubMed Central

O’Donnell, Matthew Brook; Tompson, Steven; Gonzalez, Richard; Dal Cin, Sonya; Strecher, Victor; Cummings, Kenneth Michael; An, Lawrence

2016-01-01

Mass media can powerfully affect health decision-making. Pre-testing through focus groups or surveys is a standard, though inconsistent, predictor of effectiveness. Converging evidence demonstrates that activity within brain systems associated with self-related processing can predict individual behavior in response to health messages. Preliminary evidence also suggests that neural activity in small groups can forecast population-level campaign outcomes. Less is known about the psychological processes that link neural activity and population-level outcomes, or how these predictions are affected by message content. We exposed 50 smokers to antismoking messages and used their aggregated neural activity within a ‘self-localizer’ defined region of medial prefrontal cortex to predict the success of the same campaign messages at the population level (n = 400 000 emails). Results demonstrate that: (i) independently localized neural activity during health message exposure complements existing self-report data in predicting population-level campaign responses (model combined R2 up to 0.65) and (ii) this relationship depends on message content—self-related neural processing predicts outcomes in response to strong negative arguments against smoking and not in response to compositionally similar neutral images. These data advance understanding of the psychological link between brain and large-scale behavior and may aid the construction of more effective media health campaigns. PMID:26400858

Domain-General and Domain-Specific Patterns of Activity Supporting Metacognition in Human Prefrontal Cortex

PubMed Central

2018-01-01

Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control. SIGNIFICANCE STATEMENT We used human neuroimaging to investigate processes supporting memory and perceptual metacognition. It remains controversial whether metacognition relies on a global resource that is applied to different tasks or if self-evaluative processes are specific to particular tasks. Using multivariate decoding methods, we provide evidence that perceptual- and memory-specific metacognitive representations coexist with generic confidence signals. Our findings reconcile previously conflicting results on the domain specificity/generality of metacognition and lay the groundwork for a mechanistic understanding of metacognitive judgments. PMID:29519851

Self-distancing improves interpersonal perceptions and behavior by decreasing medial prefrontal cortex activity during the provision of criticism.

PubMed

Leitner, Jordan B; Ayduk, Ozlem; Mendoza-Denton, Rodolfo; Magerman, Adam; Amey, Rachel; Kross, Ethan; Forbes, Chad E

2017-04-01

Previous research suggests that people show increased self-referential processing when they provide criticism to others, and that this self-referential processing can have negative effects on interpersonal perceptions and behavior. The current research hypothesized that adopting a self-distanced perspective (i.e. thinking about a situation from a non-first person point of view), as compared with a typical self-immersed perspective (i.e. thinking about a situation from a first-person point of view), would reduce self-referential processing during the provision of criticism, and in turn improve interpersonal perceptions and behavior. We tested this hypothesis in an interracial context since research suggests that self-referential processing plays a role in damaging interracial relations. White participants prepared for mentorship from a self-immersed or self-distanced perspective. They then conveyed negative and positive evaluations to a Black mentee while electroencephalogram (EEG) was recorded. Source analysis revealed that priming a self-distanced (vs self-immersed) perspective predicted decreased activity in regions linked to self-referential processing (medial prefrontal cortex; MPFC) when providing negative evaluations. This decreased MPFC activity during negative evaluations, in turn, predicted verbal feedback that was perceived to be more positive, warm and helpful. Results suggest that self-distancing can improve interpersonal perceptions and behavior by decreasing self-referential processing during the provision of criticism. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Distinct frontal and amygdala correlates of change detection for facial identity and expression

PubMed Central

Achaibou, Amal; Loth, Eva

2016-01-01

Recruitment of ‘top-down’ frontal attentional mechanisms is held to support detection of changes in task-relevant stimuli. Fluctuations in intrinsic frontal activity have been shown to impact task performance more generally. Meanwhile, the amygdala has been implicated in ‘bottom-up’ attentional capture by threat. Here, 22 adult human participants took part in a functional magnetic resonance change detection study aimed at investigating the correlates of successful (vs failed) detection of changes in facial identity vs expression. For identity changes, we expected prefrontal recruitment to differentiate ‘hit’ from ‘miss’ trials, in line with previous reports. Meanwhile, we postulated that a different mechanism would support detection of emotionally salient changes. Specifically, elevated amygdala activation was predicted to be associated with successful detection of threat-related changes in expression, over-riding the influence of fluctuations in top-down attention. Our findings revealed that fusiform activity tracked change detection across conditions. Ventrolateral prefrontal cortical activity was uniquely linked to detection of changes in identity not expression, and amygdala activity to detection of changes from neutral to fearful expressions. These results are consistent with distinct mechanisms supporting detection of changes in face identity vs expression, the former potentially reflecting top-down attention, the latter bottom-up attentional capture by stimulus emotional salience. PMID:26245835

Fragments of a larger whole: retrieval cues constrain observed neural correlates of memory encoding.

PubMed

Otten, Leun J

2007-09-01

Laying down a new memory involves activity in a number of brain regions. Here, it is shown that the particular regions associated with successful encoding depend on the way in which memory is probed. Event-related functional magnetic resonance imaging signals were acquired while subjects performed an incidental encoding task on a series of visually presented words denoting objects. A recognition memory test using the Remember/Know procedure to separate responses based on recollection and familiarity followed 1 day later. Critically, half of the studied objects were cued with a corresponding spoken word, and half with a corresponding picture. Regardless of cue, activity in prefrontal and hippocampal regions predicted subsequent recollection of a word. Type of retrieval cue modulated activity in prefrontal, temporal, and parietal cortices. Words subsequently recognized on the basis of a sense of familiarity were at study also associated with differential activity in a number of brain regions, some of which were probe dependent. Thus, observed neural correlates of successful encoding are constrained by type of retrieval cue, and are only fragments of all encoding-related neural activity. Regions exhibiting cue-specific effects may be sites that support memory through the degree of overlap between the processes engaged during encoding and those engaged during retrieval.

Self-affirmation activates brain systems associated with self-related processing and reward and is reinforced by future orientation.

PubMed

Cascio, Christopher N; O'Donnell, Matthew Brook; Tinney, Francis J; Lieberman, Matthew D; Taylor, Shelley E; Strecher, Victor J; Falk, Emily B

2016-04-01

Self-affirmation theory posits that people are motivated to maintain a positive self-view and that threats to perceived self-competence are met with resistance. When threatened, self-affirmations can restore self-competence by allowing individuals to reflect on sources of self-worth, such as core values. Many questions exist, however, about the underlying mechanisms associated with self-affirmation. We examined the neural mechanisms of self-affirmation with a task developed for use in a functional magnetic resonance imaging environment. Results of a region of interest analysis demonstrated that participants who were affirmed (compared with unaffirmed participants) showed increased activity in key regions of the brain's self-processing (medial prefrontal cortex + posterior cingulate cortex) and valuation (ventral striatum + ventral medial prefrontal cortex) systems when reflecting on future-oriented core values (compared with everyday activities). Furthermore, this neural activity went on to predict changes in sedentary behavior consistent with successful affirmation in response to a separate physical activity intervention. These results highlight neural processes associated with successful self-affirmation, and further suggest that key pathways may be amplified in conjunction with prospection. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics

PubMed Central

Blasi, Giuseppe; Selvaggi, Pierluigi; Fazio, Leonardo; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Zhang, Fengyu; Caforio, Grazia; Popolizio, Teresa; Apud, Jose; Weinberger, Daniel R; Bertolino, Alessandro

2015-01-01

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships. PMID:25563748

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics.

PubMed

Blasi, Giuseppe; Selvaggi, Pierluigi; Fazio, Leonardo; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Zhang, Fengyu; Caforio, Grazia; Popolizio, Teresa; Apud, Jose; Weinberger, Daniel R; Bertolino, Alessandro

2015-06-01

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind Network.

PubMed

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-04-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal-temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network.

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

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

PubMed

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

2013-10-15

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

Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

PubMed Central

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-01-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal–temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network. PMID:24247043

Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation

PubMed Central

Limb, Charles J.; Braun, Allen R.

2008-01-01

To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity. PMID:18301756

Neural substrates of spontaneous musical performance: an FMRI study of jazz improvisation.

PubMed

Limb, Charles J; Braun, Allen R

2008-02-27

To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity.

Brain connectivity changes occurring following cognitive behavioural therapy for psychosis predict long-term recovery.

PubMed

Mason, L; Peters, E; Williams, S C; Kumari, V

2017-01-17

Little is known about the psychobiological mechanisms of cognitive behavioural therapy for psychosis (CBTp) and which specific processes are key in predicting favourable long-term outcomes. Following theoretical models of psychosis, this proof-of-concept study investigated whether the long-term recovery path of CBTp completers can be predicted by the neural changes in threat-based social affective processing that occur during CBTp. We followed up 22 participants who had undergone a social affective processing task during functional magnetic resonance imaging along with self-report and clinician-administered symptom measures, before and after receiving CBTp. Monthly ratings of psychotic and affective symptoms were obtained retrospectively across 8 years since receiving CBTp, plus self-reported recovery at final follow-up. We investigated whether these long-term outcomes were predicted by CBTp-led changes in functional connections with dorsal prefrontal cortical and amygdala during the processing of threatening and prosocial facial affect. Although long-term psychotic symptoms were predicted by changes in prefrontal connections during prosocial facial affective processing, long-term affective symptoms were predicted by threat-related amygdalo-inferior parietal lobule connectivity. Greater increases in dorsolateral prefrontal cortex connectivity with amygdala following CBTp also predicted higher subjective ratings of recovery at long-term follow-up. These findings show that reorganisation occurring at the neural level following psychological therapy can predict the subsequent recovery path of people with psychosis across 8 years. This novel methodology shows promise for further studies with larger sample size, which are needed to better examine the sensitivity of psychobiological processes, in comparison to existing clinical measures, in predicting long-term outcomes.

Self-construal differences in neural responses to negative social cues.

PubMed

Liddell, Belinda J; Felmingham, Kim L; Das, Pritha; Whitford, Thomas J; Malhi, Gin S; Battaglini, Eva; Bryant, Richard A

2017-10-01

Cultures differ substantially in representations of the self. Whereas individualistic cultural groups emphasize an independent self, reflected in processing biases towards centralized salient objects, collectivistic cultures are oriented towards an interdependent self, attending to contextual associations between visual cues. It is unknown how these perceptual biases may affect brain activity in response to negative social cues. Moreover, while some studies have shown that individual differences in self-construal moderate cultural group comparisons, few have examined self-construal differences separate to culture. To investigate these issues, a final sample of a group of healthy participants high in trait levels of collectivistic self-construal (n=16) and individualistic self-construal (n=19), regardless of cultural background, completed a negative social cue evaluation task designed to engage face/object vs context-specific neural processes whilst undergoing fMRI scanning. Between-group analyses revealed that the collectivistic group exclusively engaged the parahippocampal gyrus (parahippocampal place area) - a region critical to contextual integration - during negative face processing - suggesting compensatory activations when contextual information was missing. The collectivist group also displayed enhanced negative context dependent brain activity involving the left superior occipital gyrus/cuneus and right anterior insula. By contrast, the individualistic group did not engage object or localized face processing regions as predicted, but rather demonstrated heightened appraisal and self-referential activations in medial prefrontal and temporoparietal regions to negative contexts - again suggesting compensatory processes when focal cues were absent. While individualists also appeared more sensitive to negative faces in the scenes, activating the right middle cingulate gyrus, dorsal prefrontal and parietal activations, this activity was observed relative to the scrambled baseline, and given that prefrontal and occipital regions were also engaged to neutral stimuli, may suggest an individualistic pattern to processing all social cues more generally. These findings suggest that individual differences in self-construal may be an important organizing framework facilitating perceptual processes to emotionally salient social cues, beyond the boundary of cultural group comparisons. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial.

PubMed

Watanabe, Takamitsu; Abe, Osamu; Kuwabara, Hitoshi; Yahata, Noriaki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Kawakubo, Yuki; Kamio, Yoko; Kato, Nobumasa; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori

2014-02-01

Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. Single-dose intranasal administration of oxytocin (24 IU) and placebo. Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01). These findings provide the first neurobiological evidence for oxytocin's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide. umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.

Neural priming in human frontal cortex: multiple forms of learning reduce demands on the prefrontal executive system.

PubMed

Race, Elizabeth A; Shanker, Shanti; Wagner, Anthony D

2009-09-01

Past experience is hypothesized to reduce computational demands in PFC by providing bottom-up predictive information that informs subsequent stimulus-action mapping. The present fMRI study measured cortical activity reductions ("neural priming"/"repetition suppression") during repeated stimulus classification to investigate the mechanisms through which learning from the past decreases demands on the prefrontal executive system. Manipulation of learning at three levels of representation-stimulus, decision, and response-revealed dissociable neural priming effects in distinct frontotemporal regions, supporting a multiprocess model of neural priming. Critically, three distinct patterns of neural priming were identified in lateral frontal cortex, indicating that frontal computational demands are reduced by three forms of learning: (a) cortical tuning of stimulus-specific representations, (b) retrieval of learned stimulus-decision mappings, and (c) retrieval of learned stimulus-response mappings. The topographic distribution of these neural priming effects suggests a rostrocaudal organization of executive function in lateral frontal cortex.

Functional neuroimaging of extraversion-introversion.

PubMed

Lei, Xu; Yang, Tianliang; Wu, Taoyu

2015-12-01

Neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography have provided an unprecedented neurobiological perspective for research on personality traits. Evidence from task-related neuroimaging has shown that extraversion is associated with activations in regions of the anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and the amygdala. Currently, resting-state neuroimaging is being widely used in cognitive neuroscience. Initial exploration of extraversion has revealed correlations with the medial prefrontal cortex, anterior cingulate cortex, insular cortex, and the precuneus. Recent research work has indicated that the long-range temporal dependence of the resting-state spontaneous oscillation has high test-retest reliability. Moreover, the long-range temporal dependence of the resting-state networks is highly correlated with personality traits, and this can be used for the prediction of extraversion. As the long-range temporal dependence reflects real-time information updating in individuals, this method may provide a new approach to research on personality traits.

Lateral prefrontal cortex: architectonic and functional organization

PubMed Central

Petrides, Michael

2005-01-01

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral–caudal axis and a dorsal–ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal–ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information. PMID:15937012

Conditional associative memory for musical stimuli in nonmusicians: implications for absolute pitch.

PubMed

Bermudez, Patrick; Zatorre, Robert J

2005-08-24

A previous positron emission tomography (PET) study of musicians with and without absolute pitch put forth the hypothesis that the posterior dorsolateral prefrontal cortex is involved in the conditional associative aspect of the identification of a pitch. In the work presented here, we tested this hypothesis by training eight nonmusicians to associate each of four different complex musical sounds (triad chords) with an arbitrary number in a task designed to have limited analogy to absolute-pitch identification. Each subject under-went a functional magnetic resonance imaging scanning procedure both before and after training. Active condition (identification of chords)-control condition (amplitude-matched noise bursts) comparisons for the pretraining scan showed no significant activation maxima. The same comparison for the posttraining scan revealed significant peaks of activation in posterior dorsolateral prefrontal, ventrolateral prefrontal, and parietal areas. A conjunction analysis was performed to show that the posterior dorsolateral prefrontal activity in this study is similar to that observed in the aforementioned PET study. We conclude that the posterior dorsolateral prefrontal cortex is selectively involved in the conditional association aspect of our task, as it is in the attribution of a verbal label to a note by absolute-pitch musicians.

Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.

PubMed

Kinoshita, Akihide; Takizawa, Ryu; Koike, Shinsuke; Satomura, Yoshihiro; Kawasaki, Shingo; Kawakubo, Yuki; Marumo, Kohei; Tochigi, Mamoru; Sasaki, Tsukasa; Nishimura, Yukika; Kasai, Kiyoto

2015-10-01

The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia. Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument. The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional neuroimaging of recovery from motor conversion disorder: A case report.

PubMed

Dogonowski, Anne-Marie; Andersen, Kasper W; Sellebjerg, Finn; Schreiber, Karen; Madsen, Kristoffer H; Siebner, Hartwig R

2018-03-27

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task-based activation that gradually diminished with recovery. The inverse dynamics of premotor and medial prefrontal activity over time were found during unimanual finger-tapping with the affected and non-affected hand as well as during bimanual finger-tapping. These observations suggest that reduced premotor and increased medial prefrontal activity reflect an effector-independent cortical dysfunction in conversion paresis which gradually disappears in parallel with clinical remission of paresis. The results link the medial prefrontal and dorsal premotor areas to the generation of intentional actions. We hypothesise that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Medial prefrontal cortex supports source memory accuracy for self-referenced items.

PubMed

Leshikar, Eric D; Duarte, Audrey

2012-01-01

Previous behavioral work suggests that processing information in relation to the self enhances subsequent item recognition. Neuroimaging evidence further suggests that regions along the cortical midline, particularly those of the medial prefrontal cortex (PFC), underlie this benefit. There has been little work to date, however, on the effects of self-referential encoding on source memory accuracy or whether the medial PFC might contribute to source memory for self-referenced materials. In the current study, we used fMRI to measure neural activity while participants studied and subsequently retrieved pictures of common objects superimposed on one of two background scenes (sources) under either self-reference or self-external encoding instructions. Both item recognition and source recognition were better for objects encoded self-referentially than self-externally. Neural activity predictive of source accuracy was observed in the medial PFC (Brodmann area 10) at the time of study for self-referentially but not self-externally encoded objects. The results of this experiment suggest that processing information in relation to the self leads to a mnemonic benefit for source level features, and that activity in the medial PFC contributes to this source memory benefit. This evidence expands the purported role that the medial PFC plays in self-referencing.

Predicting the practice effects on the blood oxygenation level-dependent (BOLD) function of fMRI in a symbolic manipulation task

NASA Astrophysics Data System (ADS)

Qin, Yulin; Sohn, Myeong-Ho; Anderson, John R.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Carter, Cameron S.

2003-04-01

Based on adaptive control of thought-rational (ACT-R), a cognitive architecture for cognitive modeling, researchers have developed an information-processing model to predict the blood oxygenation level-dependent (BOLD) response of functional MRI in symbol manipulation tasks. As an extension of this research, the current event-related functional MRI study investigates the effect of relatively extensive practice on the activation patterns of related brain regions. The task involved performing transformations on equations in an artificial algebra system. This paper shows that the base-level activation learning in the ACT-R theory can predict the change of the BOLD response in practice in a left prefrontal region reflecting retrieval of information. In contrast, practice has relatively little effect on the form of BOLD response in the parietal region reflecting imagined transformations to the equation or the motor region reflecting manual programming.

More attention when speaking: does it help or does it hurt?

PubMed Central

Nozari, Nazbanou; Thompson-Schill, Sharon L.

2013-01-01

Paying selective attention to a word in a multi-word utterance results in a decreased probability of error on that word (benefit), but an increased probability of error on the other words (cost). We ask whether excitation of the prefrontal cortex helps or hurts this cost. One hypothesis (the resource hypothesis) predicts a decrease in the cost due to the deployment of more attentional resources, while another (the focus hypothesis) predicts even greater costs due to further fine-tuning of selective attention. Our results are more consistent with the focus hypothesis: prefrontal stimulation caused a reliable increase in the benefit and a marginal increase in the cost of selective attention. To ensure that the effects are due to changes to the prefrontal cortex, we provide two checks: We show that the pattern of results is quite different if, instead, the primary motor cortex is stimulated. We also show that the stimulation-related benefits in the verbal task correlate with the stimulation-related benefits in an N-back task, which is known to tap into a prefrontal function. Our results shed light on how selective attention affects language production, and more generally, on how selective attention affects production of a sequence over time. PMID:24012690

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.

The role of the thalamic nuclei in recognition memory accompanied by recall during encoding and retrieval: an fMRI study.

PubMed

Pergola, Giulio; Ranft, Alexander; Mathias, Klaus; Suchan, Boris

2013-07-01

The present functional imaging study aimed at investigating the contribution of the mediodorsal nucleus and the anterior nuclei of the thalamus with their related cortical networks to recognition memory and recall. Eighteen subjects performed associative picture encoding followed by a single item recognition test during the functional magnetic resonance imaging session. After scanning, subjects performed a cued recall test using the formerly recognized pictures as cues. This post-scanning test served to classify recognition trials according to subsequent recall performance. In general, single item recognition accompanied by successful recall of the associations elicited stronger activation in the mediodorsal nucleus of the thalamus and in the prefrontal cortices both during encoding and retrieval compared to recognition without recall. In contrast, the anterior nuclei of the thalamus were selectively active during the retrieval phase of recognition followed by recall. A correlational analysis showed that activation of the anterior thalamus during retrieval as assessed by measuring the percent signal changes predicted lower rates of recognition without recall. These findings show that the thalamus is critical for recognition accompanied by recall, and provide the first evidence of a functional segregation of the thalamic nuclei with respect to the memory retrieval phase. In particular, the mediodorsal thalamic-prefrontal cortical network is activated during successful encoding and retrieval of associations, which suggests a role of this system in recall and recollection. The activity of the anterior thalamic-temporal network selectively during retrieval predicts better memory performances across subjects and this confirms the paramount role of this network in recall and recollection. Copyright © 2013 Elsevier Inc. All rights reserved.

The neural bases of distracter-resistant working memory

PubMed Central

Wager, Tor D.; Spicer, Julie; Insler, Rachel; Smith, Edward E.

2014-01-01

A major difference between humans and other animals is our capacity to maintain information in working memory (WM) while performing secondary tasks, which enables sustained, complex cognition. A common assumption is that the lateral prefrontal cortex (PFC) is critical for WM performance in the presence of distracters, but direct evidence is scarce. We assessed the relationship between fMRI activity and WM performance within-subjects, with performance matched across Distracter and No-distracter conditions. Activity in ventrolateral PFC during WM encoding and maintenance positively predicted performance in both conditions, whereas activity in the pre-supplementary motor area (pre-SMA) predicted performance only under distraction. Other parts of dorsolateral and ventrolateral PFC predicted performance only in the No-distracter condition. These findings challenge a lateral PFC-centered view of distracter-resistance, and suggest that the lateral PFC supports a type of WM representation that is efficient for dealing with task-irrelevant input but is nonetheless easily disrupted by dual-task demands. PMID:24366656

Single dose of l-dopa makes extinction memories context-independent and prevents the return of fear

PubMed Central

Haaker, Jan; Gaburro, Stefano; Sah, Anupam; Gartmann, Nina; Lonsdorf, Tina B.; Meier, Kolja; Singewald, Nicolas; Pape, Hans-Christian; Morellini, Fabio; Kalisch, Raffael

2013-01-01

Traumatic events can engender persistent excessive fear responses to trauma reminders that may return even after successful treatment. Extinction, the laboratory analog of behavior therapy, does not erase conditioned fear memories but generates competing, fear-inhibitory “extinction memories” that, however, are tied to the context in which extinction occurred. Accordingly, a dominance of fear over extinction memory expression—and, thus, return of fear—is often observed if extinguished fear stimuli are encountered outside the extinction (therapy) context. We show that postextinction administration of the dopamine precursor l-dopa makes extinction memories context-independent, thus strongly reducing the return of fear in both mice and humans. Reduced fear is accompanied by decreased amygdala and enhanced ventromedial prefrontal cortex activation in both species. In humans, ventromedial prefrontal cortex activity is predicted by enhanced resting-state functional coupling of the area with the dopaminergic midbrain during the postextinction consolidation phase. Our data suggest that dopamine-dependent boosting of extinction memory consolidation is a promising avenue to improving anxiety therapy. PMID:23754384

"I know you can hear me": neural correlates of feigned hearing loss.

PubMed

McPherson, Bradley; McMahon, Katie; Wilson, Wayne; Copland, David

2012-08-01

In the assessment of human hearing, it is often important to determine whether hearing loss is organic or nonorganic in nature. Nonorganic, or functional, hearing loss is often associated with deceptive intention on the part of the listener. Over the past decade, functional neuroimaging has been used to study the neural correlates of deception, and studies have consistently highlighted the contribution of the prefrontal cortex in such behaviors. Can patterns of brain activity be similarly used to detect when an individual is feigning a hearing loss? To answer this question, 15 adult participants were requested to respond to pure tones and simple words correctly, incorrectly, randomly, or with the intent to feign a hearing loss. As predicted, more activity was observed in the prefrontal cortices (as measured by functional magnetic resonance imaging), and delayed behavioral reaction times were noted, when the participants feigned a hearing loss or responded randomly versus when they responded correctly or incorrectly. The results suggest that cortical imaging techniques could play a role in identifying individuals who are feigning hearing loss. Copyright © 2011 Wiley Periodicals, Inc.

Individual Differences in Laughter Perception Reveal Roles for Mentalizing and Sensorimotor Systems in the Evaluation of Emotional Authenticity

PubMed Central

McGettigan, C.; Walsh, E.; Jessop, R.; Agnew, Z. K.; Sauter, D. A.; Warren, J. E.; Scott, S. K.

2015-01-01

Humans express laughter differently depending on the context: polite titters of agreement are very different from explosions of mirth. Using functional MRI, we explored the neural responses during passive listening to authentic amusement laughter and controlled, voluntary laughter. We found greater activity in anterior medial prefrontal cortex (amPFC) to the deliberate, Emitted Laughs, suggesting an obligatory attempt to determine others' mental states when laughter is perceived as less genuine. In contrast, passive perception of authentic Evoked Laughs was associated with greater activity in bilateral superior temporal gyri. An individual differences analysis found that greater accuracy on a post hoc test of authenticity judgments of laughter predicted the magnitude of passive listening responses to laughter in amPFC, as well as several regions in sensorimotor cortex (in line with simulation accounts of emotion perception). These medial prefrontal and sensorimotor sites showed enhanced positive connectivity with cortical and subcortical regions during listening to involuntary laughter, indicating a complex set of interacting systems supporting the automatic emotional evaluation of heard vocalizations. PMID:23968840

Individual differences in laughter perception reveal roles for mentalizing and sensorimotor systems in the evaluation of emotional authenticity.

PubMed

McGettigan, C; Walsh, E; Jessop, R; Agnew, Z K; Sauter, D A; Warren, J E; Scott, S K

2015-01-01

Humans express laughter differently depending on the context: polite titters of agreement are very different from explosions of mirth. Using functional MRI, we explored the neural responses during passive listening to authentic amusement laughter and controlled, voluntary laughter. We found greater activity in anterior medial prefrontal cortex (amPFC) to the deliberate, Emitted Laughs, suggesting an obligatory attempt to determine others' mental states when laughter is perceived as less genuine. In contrast, passive perception of authentic Evoked Laughs was associated with greater activity in bilateral superior temporal gyri. An individual differences analysis found that greater accuracy on a post hoc test of authenticity judgments of laughter predicted the magnitude of passive listening responses to laughter in amPFC, as well as several regions in sensorimotor cortex (in line with simulation accounts of emotion perception). These medial prefrontal and sensorimotor sites showed enhanced positive connectivity with cortical and subcortical regions during listening to involuntary laughter, indicating a complex set of interacting systems supporting the automatic emotional evaluation of heard vocalizations. © The Author 2013. Published by Oxford University Press.

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

PubMed

Kjaerby, Celia; Athilingam, Jegath; Robinson, Sarah E; Iafrati, Jillian; Sohal, Vikaas S

2016-12-13

Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings suggest a potential mechanism, linking specific receptors, synapses, patterns of circuit activity, and behavior, through which serotonin may regulate prefrontal circuit function, including anxiety-related behaviors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2018-04-18

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

Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression

PubMed Central

Liston, Conor; Chen, Ashley C.; Zebley, Benjamin D.; Drysdale, Andrew T.; Gordon, Rebecca; Leuchter, Bruce; Voss, Henning U.; Casey, B.J.; Etkin, Amit; Dubin, Marc J.

2014-01-01

Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging (rs-fMRI) to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a five-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared to a cohort of 35 healthy controls. Results Prior to treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. TMS normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. TMS also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions TMS selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response. PMID:24629537

Brain mediators of the effects of noxious heat on pain

PubMed Central

Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

2014-01-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

ERIC Educational Resources Information Center

Mulder, Martijn J.; Baeyens, Dieter; Davidson, Matthew C.; Casey, B. J.; Van Den Ban, Els; Van Engeland, Herman; Durston, Sarah

2008-01-01

The study examines whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. The results conclude that familial vulnerability to ADHD affects activity in both the prefrontal cortex and cerebellum.

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

Neural correlates of social exclusion across ages: A coordinate-based meta-analysis of functional MRI studies.

PubMed

Vijayakumar, Nandita; Cheng, Theresa W; Pfeifer, Jennifer H

2017-06-01

Given the recent surge in functional neuroimaging studies on social exclusion, the current study employed activation likelihood estimation (ALE) based meta-analyses to identify brain regions that have consistently been implicated across different experimental paradigms used to investigate exclusion. We also examined the neural correlates underlying Cyberball, the most commonly used paradigm to study exclusion, as well as differences in exclusion-related activation between developing (7-18 years of age, from pre-adolescence up to late adolescence) and emerging adult (broadly defined as undergraduates, including late adolescence and young adulthood) samples. Results revealed involvement of the bilateral medial prefrontal and posterior cingulate cortices, right precuneus and left ventrolateral prefrontal cortex across the different paradigms used to examine social exclusion; similar activation patterns were identified when restricting the analysis to Cyberball studies. Investigations into age-related effects revealed that ventrolateral prefrontal activations identified in the full sample were driven by (i.e. present in) developmental samples, while medial prefrontal activations were driven by emerging adult samples. In addition, the right ventral striatum was implicated in exclusion, but only in developmental samples. Subtraction analysis revealed significantly greater activation likelihood in striatal and ventrolateral prefrontal clusters in the developmental samples as compared to emerging adults, though the opposite contrast failed to identify any significant regions. Findings integrate the knowledge accrued from functional neuroimaging studies on social exclusion to date, highlighting involvement of lateral prefrontal regions implicated in regulation and midline structures involved in social cognitive and self-evaluative processes across experimental paradigms and ages, as well as limbic structures in developing samples specifically. Copyright © 2017 Elsevier Inc. All rights reserved.

Lateral Prefrontal Cortex Mediates the Cognitive Modification of Attentional Bias

PubMed Central

Browning, Michael; Holmes, Emily A.; Murphy, Susannah E.; Goodwin, Guy M.; Harmer, Catherine J.

2010-01-01

Background A tendency to orient attention toward threatening stimuli may be involved in the etiology of anxiety disorders. In keeping with this, both psychological and pharmacological treatments of anxiety reduce this negative attentional bias. It has been hypothesized, but not proved, that psychological interventions may alter the function of prefrontal regions supervising the allocation of attentional resources. Methods The current study examined the effects of a cognitive training regime on attention. Participants were randomly assigned to one of two training conditions: “attend-threat” training, which increases negative attentional bias, or “avoid-threat” training, which reduces it. The behavioral effects of training were assessed using a sample of 24 healthy participants. Functional magnetic resonance imaging data were collected in a further 29 healthy volunteers using a protocol that allowed the influence of both stimuli valence and attention to be discriminated. Results Cognitive training induced the expected attentional biases in healthy volunteers. Further, the training altered lateral frontal activation to emotional stimuli, with these areas responding specifically to violations of the behavioral rules learned during training. Connectivity analysis confirmed that the identified lateral frontal regions were influencing attention as indexed by activity in visual association cortex. Conclusions Our results indicate that frontal control over the processing of emotional stimuli may be tuned by psychological interventions in a manner predicted to regulate levels of anxiety. This directly supports the proposal that psychological interventions may influence attention via an effect on the prefrontal cortex. PMID:20034617

An increase in prefrontal oxygenation at the start of voluntary cycling exercise was observed independently of exercise effort and muscle mass.

PubMed

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

2018-05-31

We have reported using near-infrared spectroscopy that an increase in prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) at the start of cycling exercise has relation to central command, defined as a feedforward signal descending from higher brain centers. The final output of central command evokes the exercise effort-dependent cardiovascular responses. If the prefrontal cortex may output the final signal of central command toward the autonomic nervous system, the prefrontal oxygenation should increase depending on exercise effort. To test the hypothesis, we investigated the effects of exercise intensity and muscle mass on prefrontal oxygenation in 13 subjects. The subjects performed one- or two-legged cycling at various relative intensities for 1 min. The prefrontal Oxy-Hb and cardiovascular variables were simultaneously measured during exercise. The increase in cardiac output and the decrease in total peripheral resistance at the start of one- and two-legged cycling were augmented in proportion to exercise intensity and muscle mass recruitment. The prefrontal Oxy-Hb increased at the start of voluntary cycling, while such increase was not developed during passive cycling. Mental imagery of cycling also increased the prefrontal Oxy-Hb, concomitantly with peripheral muscle vasodilatation. However, the increase in prefrontal Oxy-Hb at the start of voluntary cycling seemed independent of exercise intensity and muscle mass recruitment. It is likely that the increased prefrontal activity at the start of cycling exercise is not representative of the final output signal of central command itself toward the autonomic nervous system but may trigger neuronal activity in the caudal brain responsible for the generation of central command.

Dorsolateral prefrontal γ-aminobutyric acid in men predicts individual differences in rash impulsivity.

PubMed

Boy, Frederic; Evans, C John; Edden, Richard A E; Lawrence, Andrew D; Singh, Krish D; Husain, Masud; Sumner, Petroc

2011-11-01

Impulsivity is a multifaceted personality construct associated with numerous psychiatric disorders. Recent research has characterized four facets of impulsivity: "urgency" (the tendency to act rashly especially in the context of distress or cravings); "lack of premeditation" (not envisaging the consequences of actions); "lack of perseverance" (not staying focused on a task); and "sensation seeking" (engaging in exciting activities). Urgency is particularly associated with clinical populations and problematic disinhibited behavior. We used magnetic resonance spectroscopy to measure concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the dorsolateral prefrontal cortex (DLPFC) in two cohorts of 12 and 13 participants. We find that variation in trait urgency in healthy men correlates with GABA concentration in the DLPFC. The result was replicated in an independent cohort. More GABA predicted lower urgency scores, consistent with a role in self-control for GABA-mediated inhibitory mechanisms in DLPFC. These findings help account for individual differences in self-control and thus clarify the relationship between GABA and a wide range of psychiatric disorders associated with impaired self-control. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Dorso-lateral prefrontal γ-amino butyric acid in men predicts individual differences in rash impulsivity

PubMed Central

Boy, Frederic; Evans, C. John; Edden, Richard A. E.; Lawrence, Andrew D.; Singh, Krish D.; Husain, Masud; Sumner, Petroc

2011-01-01

Background Impulsivity is a multifaceted personality construct associated with numerous psychiatric disorders. Recent research has characterized four facets of impulsivity: ‘urgency’ (the tendency to act rashly especially in the context of distress or cravings); ‘lack of premeditation’ (not envisaging the consequences of actions); ‘lack of perseverance’ (not staying focused on a task); ‘sensation seeking’ (engaging in exciting activities). Urgency is particularly associated with clinical populations and problematic disinhibited behaviour. Methods We used magnetic resonance spectroscopy (MRS) to measure concentration of the inhibitory neurotransmitter γ-amino butyric acid (GABA) in the dorso-lateral prefrontal cortex (dlPFC) in two cohorts of 12 and 13 participants. Results We find that variation in trait urgency in healthy men correlates with GABA concentration in the dlPFC. The result was replicated in an independent cohort. More GABA predicted lower urgency scores, consistent with a role in self-control for GABA-mediated inhibitory mechanisms in dlPFC. Conclusions These findings help account for individual differences in self-control, and thus clarify the relationship between GABA and a wide range of psychiatric disorders associated with impaired self-control. PMID:21757187

Efficient learning mechanisms hold in the social domain and are implemented in the medial prefrontal cortex

PubMed Central

Tobler, Philippe N.

2015-01-01

When we are learning to associate novel cues with outcomes, learning is more efficient if we take advantage of previously learned associations and thereby avoid redundant learning. The blocking effect represents this sort of efficiency mechanism and refers to the phenomenon in which a novel stimulus is blocked from learning when it is associated with a fully predicted outcome. Although there is sufficient evidence that this effect manifests itself when individuals learn about their own rewards, it remains unclear whether it also does when they learn about others’ rewards. We employed behavioral and neuroimaging methods to address this question. We demonstrate that blocking does indeed occur in the social domain and it does so to a similar degree as observed in the individual domain. On the neural level, activations in the medial prefrontal cortex (mPFC) show a specific contribution to blocking and learning-related prediction errors in the social domain. These findings suggest that the efficiency principle that applies to reward learning in the individual domain also applies to that in the social domain, with the mPFC playing a central role in implementing it. PMID:25326037

fNIRS Evidence of Prefrontal Regulation of Frustration in Early Childhood

PubMed Central

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

2013-01-01

The experience of frustration is common in early childhood, yet some children seem to possess a lower tolerance for frustration than others. Characterizing the biological mechanisms underlying a wide range of frustration tolerance observed in early childhood may inform maladaptive behavior and psychopathology that is associated with this construct. The goal of this study was to measure prefrontal correlates of frustration in 3–5 year-old children, who are not readily adaptable for typical neuroimaging approaches, using functional near infrared spectroscopy (fNIRS). fNIRS of frontal regions were measured as frustration was induced in children through a computer game where a desired and expected prize was “stolen” by an animated dog. A fNIRS general linear model (GLM) was used to quantify the correlation of brain regions with the task and identify areas that were statistically different between the winning and frustrating test conditions. A second-level voxel-based ANOVA analysis was then used to correlate the amplitude of each individual’s brain activation with measure of parent-reported frustration. Experimental results indicated increased activity in the middle prefrontal cortex during winning of a desired prize, while lateral prefrontal cortex activity increased during frustration. Further, activity increase in lateral prefrontal cortex during frustration correlated positively with parent-reported frustration tolerance. These findings point to the role of the lateral prefrontal cortex as a potential region supporting the regulation of emotion during frustration. PMID:23624495

An information-processing model of three cortical regions: evidence in episodic memory retrieval.

PubMed

Sohn, Myeong-Ho; Goode, Adam; Stenger, V Andrew; Jung, Kwan-Jin; Carter, Cameron S; Anderson, John R

2005-03-01

ACT-R (Anderson, J.R., et al., 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261) relates the inferior dorso-lateral prefrontal cortex to a retrieval buffer that holds information retrieved from memory and the posterior parietal cortex to an imaginal buffer that holds problem representations. Because the number of changes in a problem representation is not necessarily correlated with retrieval difficulties, it is possible to dissociate prefrontal-parietal activations. In two fMRI experiments, we examined this dissociation using the fan effect paradigm. Experiment 1 compared a recognition task, in which representation requirement remains the same regardless of retrieval difficulty, with a recall task, in which both representation and retrieval loads increase with retrieval difficulty. In the recognition task, the prefrontal activation revealed a fan effect but not the parietal activation. In the recall task, both regions revealed fan effects. In Experiment 2, we compared visually presented stimuli and aurally presented stimuli using the recognition task. While only the prefrontal region revealed the fan effect, the activation patterns in the prefrontal and the parietal region did not differ by stimulus presentation modality. In general, these results provide support for the prefrontal-parietal dissociation in terms of retrieval and representation and the modality-independent nature of the information processed by these regions. Using ACT-R, we also provide computational models that explain patterns of fMRI responses in these two areas during recognition and recall.

Reduced Structural Connectivity in Frontostriatal White Matter Tracts in the Associative Loop in Schizophrenia.

PubMed

Levitt, James J; Nestor, Paul G; Levin, Laura; Pelavin, Paula; Lin, Pan; Kubicki, Marek; McCarley, Robert W; Shenton, Martha E; Rathi, Yogesh

2017-11-01

The striatum receives segregated and integrative white matter tracts from the cortex facilitating information processing in the cortico-basal ganglia network. The authors examined both types of input tracts in the striatal associative loop in chronic schizophrenia patients and healthy control subjects. Structural and diffusion MRI scans were acquired on a 3-T system from 26 chronic schizophrenia patients and 26 matched healthy control subjects. Using FreeSurfer, the associative cortex was parcellated into ventrolateral prefrontal cortex and dorsolateral prefrontal cortex subregions. The striatum was manually parcellated into its associative and sensorimotor functional subregions. Fractional anisotropy and normalized streamlines, an estimate of fiber counts, were assessed in four frontostriatal tracts (dorsolateral prefrontal cortex-associative striatum, dorsolateral prefrontal cortex-sensorimotor striatum, ventrolateral prefrontal cortex-associative striatum, and ventrolateral prefrontal cortex-sensorimotor striatum). Furthermore, these measures were correlated with a measure of cognitive control, the Trail-Making Test, Part B. Results showed reduced fractional anisotropy and fewer streamlines in chronic schizophrenia patients for all four tracts, both segregated and integrative. Post hoc t tests showed reduced fractional anisotropy in the left ventrolateral prefrontal cortex-associative striatum and left ventrolateral prefrontal cortex-sensorimotor striatum and fewer normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum and in the left and right ventrolateral prefrontal cortex-sensorimotor striatum in chronic schizophrenia patients. Furthermore, normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum negatively correlated with Trail-Making Test, Part B, time spent in healthy control subjects but not in chronic schizophrenia patients. These findings demonstrated that structural connectivity is reduced in both segregated and integrative tracts in the striatal associative loop in chronic schizophrenia and that reduced normalized streamlines in the right-hemisphere dorsolateral prefrontal cortex-sensorimotor striatum predicted worse cognitive control in healthy control subjects but not in chronic schizophrenia patients, suggesting a loss of a "normal" brain-behavior correlation in chronic schizophrenia.

Prefrontal control and predictors of cognitive behavioral therapy response in social anxiety disorder

PubMed Central

Fitzgerald, Daniel A.; Piejko, Katherine; Roberts, Julia; Kennedy, Amy E.; Phan, K. Luan

2016-01-01

Generalized social anxiety disorder (gSAD) is associated with aberrant anterior cingulate cortex (ACC) response to threat distractors. Perceptual load has been shown to modulate ACC activity such that under high load, when demands on processing capacity is restricted, individuals with gSAD exhibit compensatory activation to threat distractors yet under low load, there is evidence of reduced activation. It is not known if neural predictors of response to cognitive behavioral therapy (CBT), based on such emotional conflict resolution, interact with demands on controlled processes. Prior to CBT, 32 patients with gSAD completed an fMRI task involving a target letter in a string of identical targets (low perceptual load) or a target letter in a mixed letter string (high perceptual load) superimposed on fearful, angry and neutral face distractors. Whole-brain voxel-wise analyses revealed better CBT outcome was predicted by more frontopartial activity that included dorsal ACC (dACC) and insula to threat (vs neutral) distractors during high, but not low, perceptual load. Psychophysiological interaction analysis with dACC as the seed region revealed less connectivity with dorsolateral prefrontal cortex to threat distractors during high load. Results indicate patients with less regulatory capability when demands on higher-order control are great may benefit more from CBT. PMID:26634281

Ventromedial prefrontal cortex encodes emotional value.

PubMed

Winecoff, Amy; Clithero, John A; Carter, R McKell; Bergman, Sara R; Wang, Lihong; Huettel, Scott A

2013-07-03

The ventromedial prefrontal cortex (vmPFC) plays a critical role in processing appetitive stimuli. Recent investigations have shown that reward value signals in the vmPFC can be altered by emotion regulation processes; however, to what extent the processing of positive emotion relies on neural regions implicated in reward processing is unclear. Here, we investigated the effects of emotion regulation on the valuation of emotionally evocative images. Two independent experimental samples of human participants performed a cognitive reappraisal task while undergoing fMRI. The experience of positive emotions activated the vmPFC, whereas the regulation of positive emotions led to relative decreases in vmPFC activation. During the experience of positive emotions, vmPFC activation tracked participants' own subjective ratings of the valence of stimuli. Furthermore, vmPFC activation also tracked normative valence ratings of the stimuli when participants were asked to experience their emotions, but not when asked to regulate them. A separate analysis of the predictive power of vmPFC on behavior indicated that even after accounting for normative stimulus ratings and condition, increased signal in the vmPFC was associated with more positive valence ratings. These results suggest that the vmPFC encodes a domain-general value signal that tracks the value of not only external rewards, but also emotional stimuli.

Increasing contextual demand modulates anterior and lateral prefrontal brain regions associated with proactive interference.

PubMed

Wolf, Robert Christian; Walter, Henrik; Vasic, Nenad

2010-01-01

Using a parametric version of a modified item-recognition paradigm with three different load levels and by means of event-related functional magnetic resonance imaging, this study tested the hypothesis that cerebral activation associated with intratrial proactive interference (PI) during working memory retrieval is influenced by increased context processing. We found activation of left BA 45 during interference trials across all levels of cognitive processing, and left lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared with high susceptibility to PI, low susceptibility was associated with activation of the left DLPFC. These results suggest that an intratrial PI effect can be modulated by increasing context processing of a transiently relevant stimulus set. Moreover, PI resolution associated with increasing context load involves multiple prefrontal regions including the ventro- and dorsolateral prefrontal cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI might be influenced by increased executive control exerted by the DLPFC.

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

PubMed

Goel, Vinod; Dolan, Raymond J

2003-12-01

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

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

PubMed

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

2014-01-01

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

Multivariate representation of food preferences in the human brain.

PubMed

Pogoda, Luca; Holzer, Matthias; Mormann, Florian; Weber, Bernd

2016-12-01

One major goal in decision neuroscience is to investigate the neuronal mechanisms being responsible for the computation of product preferences. The aim of the present fMRI study was to investigate whether similar patterns of brain activity, reflecting category dependent and category independent preference signals, can be observed in case of different food product categories (i.e. chocolate bars and salty snacks). To that end we used a multivariate searchlight approach in which a linear support vector machine (l-SVM) was trained to distinguish preferred from non-preferred chocolate bars and subsequently tested its predictive power in case of chocolate bars (within category prediction) and salty snacks (across category prediction). Preferences were measured by a binary forced choice decision paradigm before the fMRI task. In the scanner, subjects saw only one product per trial which they had to rate after presentation. Consistent with previous multi voxel pattern analysis (MVPA) studies, we found category dependent preference signals in the ventral parts of medial prefrontal cortex (mPFC), but also in dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC). Category independent preference signals were observed in the dorsal parts of mPFC, dACC, and dlPFC. While the first two results have also been reported in a closely related study, the activation in dlPFC is new in this context. We propose that the dlPFC activity does not reflect the products' value computation per se, but rather a modulatory signal which is computed in anticipation of the forthcoming product rating after stimulus presentation. Furthermore we postulate that this kind of dlPFC activation emerges only if the anticipated choices fall into the domain of primary rewards, such as foods. Thus, in contrast to previous studies which investigated preference decoding for stimuli from utterly different categories, the present study revealed some food domain specific aspects of preference processing in the human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

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 prediction errors (i.e., the difference between expectations and outcome). Although reinforcement learning has been central in explaining placebo hypoalgesia, placebo hypoalgesic effects show little extinction and persist after the discontinuation of reinforcement. Our results support the idea that conceptual treatment beliefs bias the neural processing of expectations in a treatment context compared with a more stimulus-driven processing of expectations with stimulus intensity cues. We provide evidence that this is associated with the suppression of prediction error processing in the ventral striatum by the prefrontal cortex. This provides a neural basis for persisting effects in reinforcement learning and placebo hypoalgesia. Copyright © 2017 the authors 0270-6474/17/379715-09$15.00/0.

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

PubMed

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

2013-09-01

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

Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans.

PubMed

Ito, Takehito; Kimura, Yasuyuki; Seki, Chie; Ichise, Masanori; Yokokawa, Keita; Kawamura, Kazunori; Takahashi, Hidehiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya; Yamada, Makiko

2018-06-14

The histamine H 3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H 3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H 3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H 3 receptors in the prefrontal cortex. Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H 3 receptor density was measured with the selective PET radioligand [ 11 C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H 3 receptors in this region. Higher neural activity of working memory was associated with lower H 3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H 3 receptors in working memory and indicates the potential of H 3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.

PubMed

Russell, V; Allie, S; Wiggins, T

2000-12-20

Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.

Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder.

PubMed

Martin, Donel M; Chan, Herng-Nieng; Alonzo, Angelo; Green, Melissa J; Mitchell, Philip B; Loo, Colleen K

2015-12-01

To investigate the use of transcranial direct current stimulation (tDCS) for enhancing working memory and sustained attention in euthymic patients with bipolar disorder. Fifteen patients with bipolar disorder received anodal left prefrontal tDCS with an extracephalic cathode (prefrontal condition), anodal left prefrontal and cathodal cerebellar tDCS (fronto-cerebellar condition), and sham tDCS given 'online' during performance on a working memory and sustained attention task in an intra-individual, cross-over, sham-controlled experimental design. Exploratory cluster analyses examined responders and non-responders for the different active tDCS conditions on both tasks. For working memory, approximately one-third of patients in both active tDCS conditions showed performance improvement. For sustained attention, three of 15 patients showed performance improvement with prefrontal tDCS. Responders to active tDCS for working memory performed more poorly on the task during sham tDCS compared to non-responders. A single session of active prefrontal or fronto-cerebellar tDCS failed to improve working memory or sustained attention performance in euthymic patients with bipolar disorder. Several important considerations are discussed in relation to future studies investigating tDCS for enhancing cognition in patients with bipolar disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Neural activity during affect labeling predicts expressive writing effects on well-being: GLM and SVM approaches

PubMed Central

Memarian, Negar; Torre, Jared B.; Haltom, Kate E.; Stanton, Annette L.

2017-01-01

Abstract Affect labeling (putting feelings into words) is a form of incidental emotion regulation that could underpin some benefits of expressive writing (i.e. writing about negative experiences). Here, we show that neural responses during affect labeling predicted changes in psychological and physical well-being outcome measures 3 months later. Furthermore, neural activity of specific frontal regions and amygdala predicted those outcomes as a function of expressive writing. Using supervised learning (support vector machines regression), improvements in four measures of psychological and physical health (physical symptoms, depression, anxiety and life satisfaction) after an expressive writing intervention were predicted with an average of 0.85% prediction error [root mean square error (RMSE) %]. The predictions were significantly more accurate with machine learning than with the conventional generalized linear model method (average RMSE: 1.3%). Consistent with affect labeling research, right ventrolateral prefrontal cortex (RVLPFC) and amygdalae were top predictors of improvement in the four outcomes. Moreover, RVLPFC and left amygdala predicted benefits due to expressive writing in satisfaction with life and depression outcome measures, respectively. This study demonstrates the substantial merit of supervised machine learning for real-world outcome prediction in social and affective neuroscience. PMID:28992270

Choice from non-choice: predicting consumer preferences from blood oxygenation level-dependent signals obtained during passive viewing.

PubMed

Levy, Ifat; Lazzaro, Stephanie C; Rutledge, Robb B; Glimcher, Paul W

2011-01-05

Decision-making is often viewed as a two-stage process, where subjective values are first assigned to each option and then the option of the highest value is selected. Converging evidence suggests that these subjective values are represented in the striatum and medial prefrontal cortex (MPFC). A separate line of evidence suggests that activation in the same areas represents the values of rewards even when choice is not required, as in classical conditioning tasks. However, it is unclear whether the same neural mechanism is engaged in both cases. To address this question we measured brain activation with functional magnetic resonance imaging while human subjects passively viewed individual consumer goods. We then sampled activation from predefined regions of interest and used it to predict subsequent choices between the same items made outside of the scanner. Our results show that activation in the striatum and MPFC in the absence of choice predicts subsequent choices, suggesting that these brain areas represent value in a similar manner whether or not choice is required.

Functional brain imaging predicts public health campaign success.

PubMed

Falk, Emily B; O'Donnell, Matthew Brook; Tompson, Steven; Gonzalez, Richard; Dal Cin, Sonya; Strecher, Victor; Cummings, Kenneth Michael; An, Lawrence

2016-02-01

Mass media can powerfully affect health decision-making. Pre-testing through focus groups or surveys is a standard, though inconsistent, predictor of effectiveness. Converging evidence demonstrates that activity within brain systems associated with self-related processing can predict individual behavior in response to health messages. Preliminary evidence also suggests that neural activity in small groups can forecast population-level campaign outcomes. Less is known about the psychological processes that link neural activity and population-level outcomes, or how these predictions are affected by message content. We exposed 50 smokers to antismoking messages and used their aggregated neural activity within a 'self-localizer' defined region of medial prefrontal cortex to predict the success of the same campaign messages at the population level (n = 400,000 emails). Results demonstrate that: (i) independently localized neural activity during health message exposure complements existing self-report data in predicting population-level campaign responses (model combined R(2) up to 0.65) and (ii) this relationship depends on message content-self-related neural processing predicts outcomes in response to strong negative arguments against smoking and not in response to compositionally similar neutral images. These data advance understanding of the psychological link between brain and large-scale behavior and may aid the construction of more effective media health campaigns. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Varieties of semantic ‘access’ deficit in Wernicke’s aphasia and semantic aphasia

PubMed Central

Robson, Holly; Lambon Ralph, Matthew A.; Jefferies, Elizabeth

2015-01-01

Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia, characterized by poor executive control of semantic processing across verbal and non-verbal modalities; and (ii) Wernicke’s aphasia, associated with poor auditory–verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well understood. Both patient groups exhibit some type of semantic ‘access’ deficit, as opposed to the ‘storage’ deficits observed in semantic dementia. Nevertheless, existing descriptions suggest that these patients might have different varieties of ‘access’ impairment—related to difficulty resolving competition (in semantic aphasia) versus initial activation of concepts from sensory inputs (in Wernicke’s aphasia). We used a case series design to compare patients with Wernicke’s aphasia and those with semantic aphasia on Warrington’s paradigmatic assessment of semantic ‘access’ deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic ‘blocking’ effects). Patients with Wernicke’s aphasia and semantic aphasia were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability—one that mapped onto classical ‘syndromes’ and one that did not—predicted aspects of the semantic ‘access’ deficit. Both semantic aphasia and Wernicke’s aphasia cases showed multimodal semantic impairment, although as expected, the Wernicke’s aphasia group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially ‘beneficial’ effects of stimulus repetition: cases with Wernicke’s aphasia showed initial improvement with repetition of words and pictures, while in semantic aphasia, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the ‘harmful’ effects of repetition: the ability to reselect both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, patients with semantic aphasia and Wernicke’s aphasia have partially distinct impairment of semantic ‘access’ but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks. PMID:26454668

Varieties of semantic 'access' deficit in Wernicke's aphasia and semantic aphasia.

PubMed

Thompson, Hannah E; Robson, Holly; Lambon Ralph, Matthew A; Jefferies, Elizabeth

2015-12-01

Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia, characterized by poor executive control of semantic processing across verbal and non-verbal modalities; and (ii) Wernicke's aphasia, associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well understood. Both patient groups exhibit some type of semantic 'access' deficit, as opposed to the 'storage' deficits observed in semantic dementia. Nevertheless, existing descriptions suggest that these patients might have different varieties of 'access' impairment-related to difficulty resolving competition (in semantic aphasia) versus initial activation of concepts from sensory inputs (in Wernicke's aphasia). We used a case series design to compare patients with Wernicke's aphasia and those with semantic aphasia on Warrington's paradigmatic assessment of semantic 'access' deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic 'blocking' effects). Patients with Wernicke's aphasia and semantic aphasia were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability-one that mapped onto classical 'syndromes' and one that did not-predicted aspects of the semantic 'access' deficit. Both semantic aphasia and Wernicke's aphasia cases showed multimodal semantic impairment, although as expected, the Wernicke's aphasia group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially 'beneficial' effects of stimulus repetition: cases with Wernicke's aphasia showed initial improvement with repetition of words and pictures, while in semantic aphasia, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the 'harmful' effects of repetition: the ability to reselect both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, patients with semantic aphasia and Wernicke's aphasia have partially distinct impairment of semantic 'access' but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway.

PubMed

Ruggiero, Rafael N; Rossignoli, Matheus T; Lopes-Aguiar, Cleiton; Leite, João P; Bueno-Junior, Lezio S; Romcy-Pereira, Rodrigo N

2018-06-01

Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1. Either of two forms of synaptic plasticity, long-term potentiation (LTP) or depression (LTD), were induced during pilocarpine effects, which were monitored in real time through local field potentials. We found that lithium attenuates the muscarinic potentiation of cortical LTP (<20 min) but enhances the muscarinic potentiation of LTD maintenance (>80 min). Moreover, lithium treatment promoted significant cross-frequency coupling between CA1 theta (3-5 Hz) and mPFC low-gamma (30-55 Hz) oscillations. Interestingly, lithium by itself did not affect any of these measures. Thus, lithium pretreatment and muscarinic activation synergistically modulate the hippocampal-prefrontal connectivity. Because these alterations varied with time, oscillatory parameters, and type of synaptic plasticity, our study suggests that lithium influences prefrontal-related circuits through intricate dynamics, informing future experiments on mood disorders. Copyright © 2018. Published by Elsevier Inc.

Brain activity in valuation regions while thinking about the future predicts individual discount rates.

PubMed

Cooper, Nicole; Kable, Joseph W; Kim, B Kyu; Zauberman, Gal

2013-08-07

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future--specifically, to judge the subjective length of future time intervals--predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future.

Brain Activity in Valuation Regions while Thinking about the Future Predicts Individual Discount Rates

PubMed Central

Cooper, Nicole; Kim, B. Kyu; Zauberman, Gal

2013-01-01

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future—specifically, to judge the subjective length of future time intervals—predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future. PMID:23926268

Neural correlates of coherent and biological motion perception in autism.

PubMed

Koldewyn, Kami; Whitney, David; Rivera, Susan M

2011-09-01

Recent evidence suggests those with autism may be generally impaired in visual motion perception. To examine this, we investigated both coherent and biological motion processing in adolescents with autism employing both psychophysical and fMRI methods. Those with autism performed as well as matched controls during coherent motion perception but had significantly higher thresholds for biological motion perception. The autism group showed reduced posterior Superior Temporal Sulcus (pSTS), parietal and frontal activity during a biological motion task while showing similar levels of activity in MT+/V5 during both coherent and biological motion trials. Activity in MT+/V5 was predictive of individual coherent motion thresholds in both groups. Activity in dorsolateral prefrontal cortex (DLPFC) and pSTS was predictive of biological motion thresholds in control participants but not in those with autism. Notably, however, activity in DLPFC was negatively related to autism symptom severity. These results suggest that impairments in higher-order social or attentional networks may underlie visual motion deficits observed in autism. © 2011 Blackwell Publishing Ltd.

Neural correlates of coherent and biological motion perception in autism

PubMed Central

Koldewyn, Kami; Whitney, David; Rivera, Susan M.

2011-01-01

Recent evidence suggests those with autism may be generally impaired in visual motion perception. To examine this, we investigated both coherent and biological motion processing in adolescents with autism employing both psychophysical and fMRI methods. Those with autism performed as well as matched controls during coherent motion perception but had significantly higher thresholds for biological motion perception. The autism group showed reduced posterior Superior Temporal Sulcus (pSTS), parietal and frontal activity during a biological motion task while showing similar levels of activity in MT+/V5 during both coherent and biological motion trials. Activity in MT+/V5 was predictive of individual coherent motion thresholds in both groups. Activity in dorsolateral prefrontal cortex (DLPFC) and pSTS was predictive of biological motion thresholds in control participants but not in those with autism. Notably, however, activity in DLPFC was negatively related to autism symptom severity. These results suggest that impairments in higher-order social or attentional networks may underlie visual motion deficits observed in autism. PMID:21884323

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

PubMed

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

2015-08-01

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

Impaired prefrontal activity to regulate the intrinsic motivation-action link in schizophrenia.

PubMed

Takeda, Kazuyoshi; Matsumoto, Madoka; Ogata, Yousuke; Maida, Keiko; Murakami, Hiroki; Murayama, Kou; Shimoji, Keigo; Hanakawa, Takashi; Matsumoto, Kenji; Nakagome, Kazuyuki

2017-01-01

A core feature of schizophrenia (SCZ) is impairment in intrinsic motivation. Although intrinsic motivation plays an important role in enhancing improvement of the social functioning, its neural mechanisms of impairment have yet to be clarified. We hypothesized that abnormal function of the frontostriatal loop consisting of the striatum and lateral prefrontal cortex (LPFC) may be related to impaired intrinsic motivation in SCZ. We tested this by comparing the brain activity measured by functional magnetic resonance imaging and behavioral parameters associated with movement, motivation, and cognitive control between 18 stable SCZ patients and 17 healthy control (HC) participants during a task that elicits intrinsic motivation. We also compared the functional connectivity during resting-state and the fractional anisotropy using diffusion tensor imaging analysis between the two groups. We adopted an enjoyable timing task to stop a stopwatch at an exact time, which in our previous study has demonstrated to elicit intrinsic motivation. Although the performance level in general was not different between groups, the SCZ group performed worse than the HC group in trials following "overshoot" errors (i.e., the response was too late). SCZ participants showed lower intrinsic motivation to the task than the HC group in an inventory report. The striatal activity during the prediction at the task cue period was consistently lower in SCZ participants than in HC. The LPFC activity at the task cue period positively correlated with intrinsic motivation and also with the rate of success following overshoot errors in the HC group, but not in the SCZ group. The LPFC activity at the task cue period was also positively correlated with the striatal activity in both groups. The striatal activity during the feedback period was not significantly different between groups. These results suggest that, unlike HC, the neural activity in the LPFC fails to mediate between prediction of hedonic events and cognitive control of action plans in SCZ, whereas the hedonic response is retained.

Changes in brain activity in response to problem solving during the abstinence from online game play.

PubMed

Kim, Sun Mi; Han, Doug Hyun; Lee, Young Sik; Kim, Jieun E; Renshaw, Perry F

2012-06-01

Several studies have suggested that addictive disorders including substance abuse and pathologic gambling might be associated with dysfunction on working memory and prefrontal activity. We hypothesized that excessive online game playing is associated with deficits in prefrontal cortex function and that recovery from excessive online game playing might improve prefrontal cortical activation in response to working memory stimulation. Thirteen adolescents with excessive online game playing (AEOP) and ten healthy adolescents (HC) agreed to participate in this study. The severity of online game play and playing time were evaluated for a baseline measurement and again following four weeks of treatment. Brain activation in response to working memory tasks (simple and complex calculations) at baseline and subsequent measurements was assessed using BOLD functional magnetic resonance imaging (fMRI). Compared to the HC subjects, the AEOP participants exhibited significantly greater activity in the right middle occipital gyrus, left cerebellum posterior lobe, left premotor cortex and left middle temporal gyrus in response to working memory tasks during baseline measurements. After four weeks of treatment, the AEOP subjects showed increased activity within the right dorsolateral prefrontal cortex and left occipital fusiform gyrus. After four weeks of treatment, changes in the severity of online game playing were negatively correlated with changes in the mean β value of the right dorsolateral prefrontal cortex in response to complex stimulation. We suggest that the effects of online game addiction on working memory may be similar to those observed in patients with substance dependence.

Amygdala habituation and prefrontal functional connectivity in youth with autism spectrum disorders.

PubMed

Swartz, Johnna R; Wiggins, Jillian Lee; Carrasco, Melisa; Lord, Catherine; Monk, Christopher S

2013-01-01

Amygdala habituation, the rapid decrease in amygdala responsiveness to the repeated presentation of stimuli, is fundamental to the nervous system. Habituation is important for maintaining adaptive levels of arousal to predictable social stimuli and decreased habituation is associated with heightened anxiety. Input from the ventromedial prefrontal cortex (vmPFC) regulates amygdala activity. Although previous research has shown abnormal amygdala function in youth with autism spectrum disorders (ASD), no study has examined amygdala habituation in a young sample or whether habituation is related to amygdala connectivity with the vmPFC. Data were analyzed from 32 children and adolescents with ASD and 56 typically developing controls who underwent functional magnetic resonance imaging while performing a gender identification task for faces that were fearful, happy, sad, or neutral. Habituation was tested by comparing amygdala activation to faces during the first half versus the second half of the session. VmPFC-amygdala connectivity was examined through psychophysiologic interaction analysis. Youth with ASD had decreased amygdala habituation to sad and neutral faces compared with controls. Moreover, decreased amygdala habituation correlated with autism severity as measured by the Social Responsiveness Scale. There was a group difference in vmPFC-amygdala connectivity while viewing sad faces, and connectivity predicted amygdala habituation to sad faces in controls. Sustained amygdala activation to faces suggests that repeated face presentations are processed differently in individuals with ASD, which could contribute to social impairments. Abnormal modulation of the amygdala by the vmPFC may play a role in decreased habituation. Copyright © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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…

The Neural Regions Sustaining Episodic Encoding and Recognition of Objects

ERIC Educational Resources Information Center

Hofer, Alex; Siedentopf, Christian M.; Ischebeck, Anja; Rettenbacher, Maria A.; Widschwendter, Christian G.; Verius, Michael; Golaszewski, Stefan M.; Koppelstaetter, Florian; Felber, Stephan; Wolfgang Fleischhacker, W.

2007-01-01

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral…

Theta Synchronizes the Activity of Medial Prefrontal Neurons during Learning

ERIC Educational Resources Information Center

Paz, Rony; Bauer, Elizabeth P.; Pare, Denis

2008-01-01

Memory consolidation is thought to involve the gradual transfer of transient hippocampal-dependent traces to distributed neocortical sites via the rhinal cortices. Recently, medial prefrontal (mPFC) neurons were shown to facilitate this process when their activity becomes synchronized. However, the mechanisms underlying this enhanced synchrony…

Academic stress and personality interact to increase the neural response to high-calorie food cues.

PubMed

Neseliler, Selin; Tannenbaum, Beth; Zacchia, Maria; Larcher, Kevin; Coulter, Kirsty; Lamarche, Marie; Marliss, Errol B; Pruessner, Jens; Dagher, Alain

2017-09-01

Psychosocial stress is associated with an increased intake of palatable foods and weight gain in stress-reactive individuals. Personality traits have been shown to predict stress-reactivity. However, it is not known if personality traits influence brain activity in regions implicated in appetite control during psychosocial stress. The current study assessed whether Gray's Behavioural Inhibition System (BIS) scale, a measure of stress-reactivity, was related to the activity of brain regions implicated in appetite control during a stressful period. Twenty-two undergraduate students participated in a functional magnetic resonance imaging (fMRI) experiment once during a non-exam period and once during final exams in a counter-balanced order. In the scanner, they viewed food and scenery pictures. In the exam compared with the non-exam condition, BIS scores related to increased perceived stress and correlated with increased blood-oxygen-level dependent (BOLD) response to high-calorie food images in regions implicated in food reward and subjective value, such as the ventromedial prefrontal cortex, (vmPFC) and the amygdala. BIS scores negatively related to the functional connectivity between the vmPFC and the dorsolateral prefrontal cortex. The results demonstrate that the BIS trait influences stress reactivity. This is observed both as an increased activity in brain regions implicated in computing the value of food cues and decreased connectivity of these regions to prefrontal regions implicated in self-control. This suggests that the effects of real life stress on appetitive brain function and self-control is modulated by a personality trait. This may help to explain why stressful periods can lead to overeating in vulnerable individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prefrontal inhibition of threat processing reduces working memory interference

PubMed Central

Clarke, Robert; Johnstone, Tom

2013-01-01

Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM) task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modeling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesized that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat-related interference. PMID:23750133

Gender differences in brain activity generated by unpleasant word stimuli concerning body image: an fMRI study.

PubMed

Shirao, Naoko; Okamoto, Yasumasa; Mantani, Tomoyuki; Okamoto, Yuri; Yamawaki, Shigeto

2005-01-01

We have previously reported that the temporomesial area, including the amygdala, is activated in women when processing unpleasant words concerning body image. To detect gender differences in brain activation during processing of these words. Functional magnetic resonance imaging was used to investigate 13 men and 13 women during an emotional decision task consisting of unpleasant words concerning body image and neutral words. The left medial prefrontal cortex and hippocampus were activated only among men, and the left amygdala was activated only among women during the task; activation in the apical prefrontal region was significantly greater in men than in women. Our data suggest that the prefrontal region is responsible for the gender differences in the processing of words concerning body image, and may also be responsible for gender differences in susceptibility to eating disorders.

Level of processing modulates the neural correlates of emotional memory formation

PubMed Central

Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

2010-01-01

Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study employed a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. FMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral prefrontal cortex demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information. PMID:20350176

Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias.

PubMed

Ott, Derek V M; Ullsperger, Markus; Jocham, Gerhard; Neumann, Jane; Klein, Tilmann A

2011-07-15

The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

Beta Oscillatory Dynamics in the Prefrontal and Superior Temporal Cortices Predict Spatial Working Memory Performance.

PubMed

Proskovec, Amy L; Wiesman, Alex I; Heinrichs-Graham, Elizabeth; Wilson, Tony W

2018-05-31

The oscillatory dynamics serving spatial working memory (SWM), and how such dynamics relate to performance, are poorly understood. To address these topics, the present study recruited 22 healthy adults to perform a SWM task during magnetoencephalography (MEG). The resulting MEG data were transformed into the time-frequency domain, and significant oscillatory responses were imaged using a beamformer. Voxel time series data were extracted from the cluster peaks to quantify the dynamics, while whole-brain partial correlation maps were computed to identify regions where oscillatory strength varied with accuracy on the SWM task. The results indicated transient theta oscillations in spatially distinct subregions of the prefrontal cortices at the onset of encoding and maintenance, which may underlie selection of goal-relevant information. Additionally, strong and persistent decreases in alpha and beta oscillations were observed throughout encoding and maintenance in parietal, temporal, and occipital regions, which could serve sustained attention and maintenance processes during SWM performance. The neuro-behavioral correlations revealed that beta activity within left dorsolateral prefrontal control regions and bilateral superior temporal integration regions was negatively correlated with SWM accuracy. Notably, this is the first study to employ a whole-brain approach to significantly link neural oscillations to behavioral performance in the context of SWM.

Enriched Encoding: Reward Motivation Organizes Cortical Networks for Hippocampal Detection of Unexpected Events

PubMed Central

Murty, Vishnu P.; Adcock, R. Alison

2014-01-01

Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical–hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions—a potentially unique contribution of the hippocampus to reward learning. PMID:23529005

Atypical prefrontal cortical responses to joint/non-joint attention in children with autism spectrum disorder (ASD): A functional near-infrared spectroscopy study

PubMed Central

Zhu, Huilin; Li, Jun; Fan, Yuebo; Li, Xinge; Huang, Dan; He, Sailing

2015-01-01

Autism spectrum disorder (ASD) is a neuro-developmental disorder, characterized by impairments in one’s capacity for joint attention. In this study, functional near-infrared spectroscopy (fNIRS) was applied to study the differences in activation and functional connectivity in the prefrontal cortex between children with autism spectrum disorder (ASD) and typically developing (TD) children. 21 ASD and 20 TD children were recruited to perform joint and non-joint attention tasks. Compared with TD children, children with ASD showed reduced activation and atypical functional connectivity pattern in the prefrontal cortex during joint attention. The atypical development of left prefrontal cortex might play an important role in social cognition defects of children with ASD. PMID:25798296

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

PubMed

Goel, Vinod; Dolan, Raymond J

2004-10-01

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

Someone has to give in: theta oscillations correlate with adaptive behavior in social bargaining

PubMed Central

Zamorano, Francisco; López, Tamara; Rodriguez, Carlos; Cosmelli, Diego; Aboitiz, Francisco

2014-01-01

During social bargain, one has to both figure out the others’ intentions and behave strategically in such a way that the others’ behaviors will be consistent with one’s expectations. To understand the neurobiological mechanisms underlying these behaviors, we used electroencephalography while subjects played as proposers in a repeated ultimatum game. We found that subjects adapted their offers to obtain more acceptances in the last round and that this adaptation correlated negatively with prefrontal theta oscillations. People with higher prefrontal theta activity related to a rejection did not adapt their offers along the game to maximize their earning. Moreover, between-subject variation in posterior theta oscillations correlated positively with how individual theta activity influenced the change of offer after a rejection, reflecting a process of behavioral adaptation to the others’ demands. Interestingly, people adapted better their offers when they knew that they where playing against a computer, although the behavioral adaptation did not correlate with prefrontal theta oscillation. Behavioral changes between human and computer games correlated with prefrontal theta activity, suggesting that low adaptation in human games could be a strategy. Taken together, these results provide evidence for specific roles of prefrontal and posterior theta oscillations in social bargaining. PMID:24493841

Magnetic stimulation of the dorsolateral prefrontal cortex dissociates fragile visual short-term memory from visual working memory.

PubMed

Sligte, Ilja G; Wokke, Martijn E; Tesselaar, Johannes P; Scholte, H Steven; Lamme, Victor A F

2011-05-01

To guide our behavior in successful ways, we often need to rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). While VSTM is usually broken down into iconic memory (brief and high-capacity store) and visual working memory (sustained, yet limited-capacity store), recent studies have suggested the existence of an additional and intermediate form of VSTM that depends on activity in extrastriate cortex. In previous work, we have shown that this fragile form of VSTM can be dissociated from iconic memory. In the present study, we provide evidence that fragile VSTM is different from visual working memory as magnetic stimulation of the right dorsolateral prefrontal cortex (DLPFC) disrupts visual working memory, while leaving fragile VSTM intact. In addition, we observed that people with high DLPFC activity had superior working memory capacity compared to people with low DLPFC activity, and only people with high DLPFC activity really showed a reduction in working memory capacity in response to magnetic stimulation. Altogether, this study shows that VSTM consists of three stages that have clearly different characteristics and rely on different neural structures. On the methodological side, we show that it is possible to predict individual susceptibility to magnetic stimulation based on functional MRI activity. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Identifying the Neural Substrates of Procrastination: a Resting-State fMRI Study.

PubMed

Zhang, Wenwen; Wang, Xiangpeng; Feng, Tingyong

2016-09-12

Procrastination is a prevalent problematic behavior that brings serious consequences to individuals who suffer from it. Although this phenomenon has received increasing attention from researchers, the underpinning neural substrates of it is poorly studied. To examine the neural bases subserving procrastination, the present study employed resting-state fMRI. The main results were as follows: (1) the behavioral procrastination was positively correlated with the regional activity of the ventromedial prefrontal cortex (vmPFC) and the parahippocampal cortex (PHC), while negatively correlated with that of the anterior prefrontal cortex (aPFC). (2) The aPFC-seed connectivity with the anterior medial prefrontal cortex and the posterior cingulate cortex was positively associated with procrastination. (3) The connectivity between vmPFC and several other regions, such as the dorsomedial prefrontal cortex, the bilateral inferior prefrontal cortex showed a negative association with procrastination. These results suggested that procrastination could be attributed to, on the one hand, hyper-activity of the default mode network (DMN) that overrides the prefrontal control signal; while on the other hand, the failure of top-down control exerted by the aPFC on the DMN. Therefore, the present study unravels the biomarkers of procrastination and provides treatment targets for procrastination prevention.

Identifying the Neural Substrates of Procrastination: a Resting-State fMRI Study

PubMed Central

Zhang, Wenwen; Wang, Xiangpeng; Feng, Tingyong

2016-01-01

Procrastination is a prevalent problematic behavior that brings serious consequences to individuals who suffer from it. Although this phenomenon has received increasing attention from researchers, the underpinning neural substrates of it is poorly studied. To examine the neural bases subserving procrastination, the present study employed resting-state fMRI. The main results were as follows: (1) the behavioral procrastination was positively correlated with the regional activity of the ventromedial prefrontal cortex (vmPFC) and the parahippocampal cortex (PHC), while negatively correlated with that of the anterior prefrontal cortex (aPFC). (2) The aPFC-seed connectivity with the anterior medial prefrontal cortex and the posterior cingulate cortex was positively associated with procrastination. (3) The connectivity between vmPFC and several other regions, such as the dorsomedial prefrontal cortex, the bilateral inferior prefrontal cortex showed a negative association with procrastination. These results suggested that procrastination could be attributed to, on the one hand, hyper-activity of the default mode network (DMN) that overrides the prefrontal control signal; while on the other hand, the failure of top-down control exerted by the aPFC on the DMN. Therefore, the present study unravels the biomarkers of procrastination and provides treatment targets for procrastination prevention. PMID:27616687

More attention when speaking: does it help or does it hurt?

PubMed

Nozari, Nazbanou; Thompson-Schill, Sharon L

2013-11-01

Paying selective attention to a word in a multi-word utterance results in a decreased probability of error on that word (benefit), but an increased probability of error on the other words (cost). We ask whether excitation of the prefrontal cortex helps or hurts this cost. One hypothesis (the resource hypothesis) predicts a decrease in the cost due to the deployment of more attentional resources, while another (the focus hypothesis) predicts even greater costs due to further fine-tuning of selective attention. Our results are more consistent with the focus hypothesis: prefrontal stimulation caused a reliable increase in the benefit and a marginal increase in the cost of selective attention. To ensure that the effects are due to changes to the prefrontal cortex, we provide two checks: We show that the pattern of results is quite different if, instead, the primary motor cortex is stimulated. We also show that the stimulation-related benefits in the verbal task correlate with the stimulation-related benefits in an N-back task, which is known to tap into a prefrontal function. Our results shed light on how selective attention affects language production, and more generally, on how selective attention affects production of a sequence over time. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neural and psychophysiological correlates of human performance under stress and high mental workload.

PubMed

Mandrick, Kevin; Peysakhovich, Vsevolod; Rémy, Florence; Lepron, Evelyne; Causse, Mickaël

2016-12-01

In our anxiogenic and stressful world, the maintenance of an optimal cognitive performance is a constant challenge. It is particularly true in complex working environments (e.g. flight deck, air traffic control tower), where individuals have sometimes to cope with a high mental workload and stressful situations. Several models (i.e. processing efficiency theory, cognitive-energetical framework) have attempted to provide a conceptual basis on how human performance is modulated by high workload and stress/anxiety. These models predict that stress can reduce human cognitive efficiency, even in the absence of a visible impact on the task performance. Performance may be protected under stress thanks to compensatory effort, but only at the expense of a cognitive cost. Yet, the psychophysiological cost of this regulation remains unclear. We designed two experiments involving pupil diameter, cardiovascular and prefrontal oxygenation measurements. Participants performed the Toulouse N-back Task that intensively engaged both working memory and mental calculation processes under the threat (or not) of unpredictable aversive sounds. The results revealed that higher task difficulty (higher n level) degraded the performance and induced an increased tonic pupil diameter, heart rate and activity in the lateral prefrontal cortex, and a decreased phasic pupil response and heart rate variability. Importantly, the condition of stress did not impact the performance, but at the expense of a psychophysiological cost as demonstrated by lower phasic pupil response, and greater heart rate and prefrontal activity. Prefrontal cortex seems to be a central region for mitigating the influence of stress because it subserves crucial functions (e.g. inhibition, working memory) that can promote the engagement of coping strategies. Overall, findings confirmed the psychophysiological cost of both mental effort and stress. Stress likely triggered increased motivation and the recruitment of additional cognitive resources that minimize its aversive effects on task performance (effectiveness), but these compensatory efforts consumed resources that caused a loss of cognitive efficiency (ratio between performance effectiveness and mental effort). Copyright © 2016 Elsevier B.V. All rights reserved.

Behavioral activation system modulation on brain activation during appetitive and aversive stimulus processing.

PubMed

Barrós-Loscertales, Alfonso; Ventura-Campos, Noelia; Sanjuán-Tomás, Ana; Belloch, Vicente; Parcet, Maria-Antònia; Avila, César

2010-03-01

The reinforcement sensitivity theory (RST) proposed the behavioral activation system (BAS) as a neurobehavioral system that is dependent on dopamine-irrigated structures and that mediates the individual differences in sensitivity and reactivity to appetitive stimuli associated with BAS-related personality traits. Theoretical developments propose that high BAS sensitivity is associated with both enhanced appetitive stimuli processing and the diminished processing of aversive stimuli. The objective of this study was to analyze how individual differences in BAS functioning were associated with brain activation during erotic and aversive picture processing while subjects were involved in a simple goal-directed task. Forty-five male participants took part in this study. The task activation results confirm the activation of the reward and punishment brain-related structures while viewing erotic and aversive pictures, respectively. The SR scores show a positive correlation with activation of the left lateral prefrontal cortex, the mesial prefrontal cortex and the right occipital cortex while viewing erotic pictures, and a negative correlation with the right lateral prefrontal cortex and the left occipital cortex while viewing aversive pictures. In summary, the SR scores modulate the activity of the cortical areas in the prefrontal and the occipital cortices that are proposed to modulate the BAS and the BIS-FFFS.

Loss anticipation and outcome during the Monetary Incentive Delay Task: a neuroimaging systematic review and meta-analysis

PubMed Central

Dugré, Jules R.; Dumais, Alexandre; Bitar, Nathalie

2018-01-01

Background Reward seeking and avoidance of punishment are key motivational processes. Brain-imaging studies often use the Monetary Incentive Delay Task (MIDT) to evaluate motivational processes involved in maladaptive behavior. Although the bulk of research has been done on the MIDT reward events, little is known about the neural basis of avoidance of punishment. Therefore, we conducted a meta-analysis of brain activations during anticipation and receipt of monetary losses in healthy controls. Methods All functional neuro-imaging studies using the MIDT in healthy controls were retrieved using PubMed, Google Scholar & EMBASE databases. Functional neuro-imaging data was analyzed using the Seed-based d Mapping Software. Results Thirty-five studies met the inclusion criteria, comprising 699 healthy adults. In both anticipation and loss outcome phases, participants showed large and robust activations in the bilateral striatum, (anterior) insula, and anterior cingulate gyrus relatively to Loss > Neutral contrast. Although relatively similar activation patterns were observed during the two event types, they differed in the pattern of prefrontal activations: ventro-lateral prefrontal activations were observed during loss anticipation, while medial prefrontal activations were observed during loss receipt. Discussion Considering that previous meta-analyses highlighted activations in the medial prefrontal cortex/anterior cingulate cortex, the anterior insula and the ventral striatum, the current meta-analysis highlighted the potential specificity of the ventro-lateral prefrontal regions, the median cingulate cortex and the amygdala in the loss events. Future studies can rely on these latter results to examine the neural correlates of loss processing in psychiatric populations characterized by harm avoidance or insensitivity to punishment. PMID:29761060

Loss anticipation and outcome during the Monetary Incentive Delay Task: a neuroimaging systematic review and meta-analysis.

PubMed

Dugré, Jules R; Dumais, Alexandre; Bitar, Nathalie; Potvin, Stéphane

2018-01-01

Reward seeking and avoidance of punishment are key motivational processes. Brain-imaging studies often use the Monetary Incentive Delay Task (MIDT) to evaluate motivational processes involved in maladaptive behavior. Although the bulk of research has been done on the MIDT reward events, little is known about the neural basis of avoidance of punishment. Therefore, we conducted a meta-analysis of brain activations during anticipation and receipt of monetary losses in healthy controls. All functional neuro-imaging studies using the MIDT in healthy controls were retrieved using PubMed, Google Scholar & EMBASE databases. Functional neuro-imaging data was analyzed using the Seed-based d Mapping Software. Thirty-five studies met the inclusion criteria, comprising 699 healthy adults. In both anticipation and loss outcome phases, participants showed large and robust activations in the bilateral striatum, (anterior) insula, and anterior cingulate gyrus relatively to Loss > Neutral contrast. Although relatively similar activation patterns were observed during the two event types, they differed in the pattern of prefrontal activations: ventro-lateral prefrontal activations were observed during loss anticipation, while medial prefrontal activations were observed during loss receipt. Considering that previous meta-analyses highlighted activations in the medial prefrontal cortex/anterior cingulate cortex, the anterior insula and the ventral striatum, the current meta-analysis highlighted the potential specificity of the ventro-lateral prefrontal regions, the median cingulate cortex and the amygdala in the loss events. Future studies can rely on these latter results to examine the neural correlates of loss processing in psychiatric populations characterized by harm avoidance or insensitivity to punishment.

Targeting the Dopamine 1 Receptor or its Downstream Signalling by Inhibiting Phosphodiesterase-1 Improves Cognitive Performance.

PubMed

Pekcec, Anton; Schülert, Niklas; Stierstorfer, Birgit; Deiana, Serena; Dorner-Ciossek, Cornelia; Rosenbrock, Holger

2018-05-03

Insufficient prefrontal dopamine 1 (D1) receptor signalling has been linked to cognitive dysfunction in several psychiatric conditions. Because the phosphodiesterase-1 (PDE1) isoform B (PDE1B) is postulated to regulate D1 receptor-dependent signal transduction, this study intended to elucidate the role of PDE1 for cognitive processes reliant on D1 receptor function. Cognitive performance of the D1 receptor agonist, SKF38393, was studied in the T-maze continuous alternation task and the 5-Choice Serial Reaction Time Task. D1 receptor/ PDE1B double-immunohistochemistry was performed using human and rat prefrontal brain sections. Pharmacological activity of the PDE1 inhibitor, ITI-214, was assessed by measuring the increase of cAMP/ cGMP in prefrontal brain tissue and its effect on working memory performance. Mechanistic studies on modulation of prefrontal neuronal transmission by SKF38393 and ITI-214 were performed using extracellular recordings in brain slices. SKF38393 improved working memory and attentional performance in rodents. D1 receptor/ PDE1B co-expression was verified in both, human and rat prefrontal brain sections. The pharmacological activity of ITI-214 on its target was demonstrated by increased prefrontal cAMP/ cGMP upon administration. In addition, ITI-214 improved working memory performance. SKF38393 and ITI-214 facilitated neuronal transmission in prefrontal brain slices. We hypothesise that PDE1 inhibition may improve working memory performance by increasing prefrontal synaptic transmission and/or postsynaptic D1 receptor signalling, by modulating prefrontal downstream second messenger levels. These data may therefore support the use of PDE1 inhibitors as a potential approach for the treatment of cognitive dysfunction. This article is protected by copyright. All rights reserved.

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

PubMed

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

2016-09-22

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

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

PubMed

Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

2010-02-01

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Learning-Induced Plasticity in Medial Prefrontal Cortex Predicts Preference Malleability

PubMed Central

Garvert, Mona M.; Moutoussis, Michael; Kurth-Nelson, Zeb; Behrens, Timothy E.J.; Dolan, Raymond J.

2015-01-01

Summary Learning induces plasticity in neuronal networks. As neuronal populations contribute to multiple representations, we reasoned plasticity in one representation might influence others. We used human fMRI repetition suppression to show that plasticity induced by learning another individual’s values impacts upon a value representation for oneself in medial prefrontal cortex (mPFC), a plasticity also evident behaviorally in a preference shift. We show this plasticity is driven by a striatal “prediction error,” signaling the discrepancy between the other’s choice and a subject’s own preferences. Thus, our data highlight that mPFC encodes agent-independent representations of subjective value, such that prediction errors simultaneously update multiple agents’ value representations. As the resulting change in representational similarity predicts interindividual differences in the malleability of subjective preferences, our findings shed mechanistic light on complex human processes such as the powerful influence of social interaction on beliefs and preferences. PMID:25611512

Frontal lobe activation during object alternation acquisition.

PubMed

Zald, David H; Curtis, Clayton; Chernitsky, Laura A; Pardo, José V

2005-01-01

Object alternation (OA) tasks are increasingly used as probes of ventral prefrontal functioning in humans. In the most common variant of the OA task, subjects must deduce the task rule through trial-and-error learning. To examine the neural correlates of OA acquisition, the authors measured regional cerebral blood flow with positron emission tomography while subjects acquired an OA task, performed a sensorimotor control condition, or performed already learned and practiced OA. As expected, activations emerged in the ventral prefrontal cortex. However, activation of the presupplemental motor area was more closely associated with successful task performance. The authors suggest that areas beyond the ventral prefrontal cortex are critically involved in OA acquisition. 2005 APA

The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness.

PubMed

Huang, Zirui; Obara, Natsuho; Davis, Henry Hap; Pokorny, Johanna; Northoff, Georg

2016-02-01

Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ventromedial prefrontal cortex activity and rapid eye movement sleep are associated with subsequent fear expression in human subjects.

PubMed

Spoormaker, V I; Gvozdanovic, G A; Sämann, P G; Czisch, M

2014-05-01

In humans, activity patterns in the ventromedial prefrontal cortex (vmPFC) have been found to be predictive of subsequent fear memory consolidation. Pioneering work in rodents has further shown that vmPFC-amygdala theta synchronization is correlated with fear memory consolidation. We aimed to evaluate whether vmPFC activity during fear conditioning is (1) correlated with fear expression the subsequent day and whether (2) this relationship is mediated by rapid eye movement (REM) sleep. We analyzed data from 17 young healthy subjects undergoing a fear conditioning task, followed by a fear extinction task 24 h later, both recorded with simultaneous skin conductance response (SCR) and functional magnetic resonance imaging measurements, with a polysomnographically recorded night sleep in between. Our results showed a correlation between vmPFC activity during fear conditioning and subsequent REM sleep amount, as well as between REM sleep amount and SCR to the conditioned stimulus 24 h later. Moreover, we observed a significant correlation between vmPFC activity during fear conditioning and SCR responses during extinction, which was no longer significant after controlling for REM sleep amount. vmPFC activity during fear conditioning was further correlated with sleep latency. Interestingly, hippocampus activity during fear conditioning was correlated with stage 2 and stage 4 sleep amount. Our results provide preliminary evidence that the relationship between REM sleep and fear conditioning and extinction observed in rodents can be modeled in healthy human subjects, highlighting an interrelated set of potentially relevant trait markers.

Topography of activation deficits in schizophrenia during P300 task related to cognition and structural connectivity.

PubMed

Molina, Vicente; Bachiller, Alejandro; de Luis, Rodrigo; Lubeiro, Alba; Poza, Jesús; Hornero, Roberto; Alonso, Joan Francesc; Mañanas, Miguel Angel; Marqués, Patricia; Romero, Sergio

2018-02-02

The study of cerebral underpinnings of schizophrenia may benefit from the high temporal resolution of electromagnetic techniques, but its spatial resolution is low. However, source imaging approaches such as low-resolution brain electromagnetic tomography (LORETA) allow for an acceptable compromise between spatial and temporal resolutions. We combined LORETA with 32 channels and 3-Tesla diffusion magnetic resonance (Dmr) to study cerebral dysfunction in 38 schizophrenia patients (17 first episodes, FE), compared to 53 healthy controls. The EEG was acquired with subjects performing an odd-ball task. Analyses included an adaptive window of interest to take into account the interindividual variability of P300 latency. We compared source activation patters to distractor (P3a) and target (P3b) tones within- and between-groups. Patients showed a reduced activation in anterior cingulate and lateral and medial prefrontal cortices, as well as inferior/orbital frontal regions. This was also found in the FE patients alone. The activation was directly related to IQ in the patients and controls and to working memory performance in controls. Symptoms were unrelated to source activation. Fractional anisotropy in the tracts connecting lateral prefrontal and anterior cingulate regions predicted source activation in these regions in the patients. These results replicate the source activation deficit found in a previous study with smaller sample size and a lower number of sensors and suggest an association between structural connectivity deficits and functional alterations.

Task-Dependent Modulations of Prefrontal and Hippocampal Activity during Intrinsic Word Production

ERIC Educational Resources Information Center

Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

2009-01-01

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on…

Neural correlates of social motivation: an fMRI study on power versus affiliation.

PubMed

Quirin, Markus; Meyer, Frank; Heise, Nils; Kuhl, Julius; Küstermann, Ekkehard; Strüber, Daniel; Cacioppo, John T

2013-06-01

Power versus affiliation motivations refer to two different strivings relevant in the context of social relationships. We used functional magnetic resonance imaging (fMRI) to determine neural structures involved in power versus affiliation motivation based on an individual differences approach. Seventeen participants provided self-reports of power and affiliation motives and were presented with love, power-related, and control movie clips. The power motive predicted activity in four clusters within the left prefrontal cortex (PFC), while participants viewed power-related film clips. The affiliation motive predicted activity in the right putamen/pallidum while participants viewed love stories. The present findings extend previous research on social motivations to the level of neural functioning and suggest differential networks for power-related versus affiliation-related social motivations. Copyright © 2012 Elsevier B.V. All rights reserved.

Diminished medial prefrontal cortex activation during the recollection of stressful events is an acquired characteristic of PTSD.

PubMed

Dahlgren, M K; Laifer, L M; VanElzakker, M B; Offringa, R; Hughes, K C; Staples-Bradley, L K; Dubois, S J; Lasko, N B; Hinojosa, C A; Orr, S P; Pitman, R K; Shin, L M

2018-05-01

Previous research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD. In this case-control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement. Diminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups. Diminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response.

Resting lateralized activity predicts the cortical response and appraisal of emotions: an fNIRS study.

PubMed

Balconi, Michela; Grippa, Elisabetta; Vanutelli, Maria Elide

2015-12-01

This study explored the effect of lateralized left-right resting brain activity on prefrontal cortical responsiveness to emotional cues and on the explicit appraisal (stimulus evaluation) of emotions based on their valence. Indeed subjective responses to different emotional stimuli should be predicted by brain resting activity and should be lateralized and valence-related (positive vs negative valence). A hemodynamic measure was considered (functional near-infrared spectroscopy). Indeed hemodynamic resting activity and brain response to emotional cues were registered when subjects (N = 19) viewed emotional positive vs negative stimuli (IAPS). Lateralized index response during resting state, LI (lateralized index) during emotional processing and self-assessment manikin rating were considered. Regression analysis showed the significant predictive effect of resting activity (more left or right lateralized) on both brain response and appraisal of emotional cues based on stimuli valence. Moreover, significant effects were found as a function of valence (more right response to negative stimuli; more left response to positive stimuli) during emotion processing. Therefore, resting state may be considered a predictive marker of the successive cortical responsiveness to emotions. The significance of resting condition for emotional behavior was discussed. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Brain mediators of the effects of noxious heat on pain.

PubMed

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Neural Activity During Health Messaging Predicts Reductions in Smoking Above and Beyond Self-Report

PubMed Central

Falk, Emily B.; Berkman, Elliot T.; Whalen, Danielle; Lieberman, Matthew D.

2011-01-01

Objective The current study tested whether neural activity in response to messages designed to help smokers quit could predict smoking reduction, above and beyond self-report. Design Using neural activity in an a priori region of interest (a subregion of medial prefrontal cortex [MPFC]), in response to ads designed to help smokers quit smoking, we prospectively predicted reductions in smoking in a community sample of smokers (N = 28) who were attempting to quit smoking. Smoking was assessed via expired carbon monoxide (CO; a biological measure of recent smoking) at baseline and 1 month following exposure to professionally developed quitting ads. Results A positive relationship was observed between activity in the MPFC region of interest and successful quitting (increased activity in MPFC was associated with a greater decrease in expired CO). The addition of neural activity to a model predicting changes in CO from self-reported intentions, self-efficacy, and ability to relate to the messages significantly improved model fit, doubling the variance explained ( Rself−report2=.15,Rself−report+neuralactivity2=.35,Rchange2=.20). Conclusion: Neural activity is a useful complement to existing self-report measures. In this investigation, we extend prior work predicting behavior change based on neural activity in response to persuasive media to an important health domain and discuss potential psychological interpretations of the brain–behavior link. Our results support a novel use of neuroimaging technology for understanding the psychology of behavior change and facilitating health promotion. PMID:21261410

The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization.

PubMed

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

2016-01-15

Previous studies have shown that higher aerobic fitness is related to higher cognitive function and higher task-related prefrontal activation in older adults. However, a holistic picture of these factors has yet to be presented. As a typical age-related change of brain activation, less lateralized activity in the prefrontal cortex during cognitive tasks has been observed in various neuroimaging studies. Thus, this study aimed to reveal the relationship between aerobic fitness, cognitive function, and frontal lateralization. Sixty male older adults each performed a submaximal incremental exercise test to determine their oxygen intake (V·O2) at ventilatory threshold (VT) in order to index their aerobic fitness. They performed a color-word Stroop task while prefrontal activation was monitored using functional near infrared spectroscopy. As an index of cognitive function, Stroop interference time was analyzed. Partial correlation analyses revealed significant correlations among higher VT, shorter Stroop interference time and greater left-lateralized dorsolateral prefrontal cortex (DLPFC) activation when adjusting for education. Moreover, mediation analyses showed that left-lateralized DLPFC activation significantly mediated the association between VT and Stroop interference time. These results suggest that higher aerobic fitness is associated with cognitive function via lateralized frontal activation in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function.

PubMed

Lodge, Daniel J

2011-05-01

The prefrontal cortex (PFC) is essential for top-down control over higher-order executive function. In this study we demonstrate that the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) differentially regulate VTA dopamine neuron activity, and furthermore, the pattern of activity in the PFC drastically alters the dopamine neuron response. Thus, although single-pulse activation of the mPFC either excites or inhibits equivalent numbers of dopamine neurons, activation of the OFC induces a primarily inhibitory response. Moreover, activation of the PFC with a pattern that mimics spontaneous burst firing of pyramidal neurons produces a strikingly different response. Specifically, burst-like activation of the mPFC induces a massive increase in dopamine neuron firing, whereas a similar pattern of OFC activation largely inhibits dopamine activity. Taken together, these data demonstrate that the mPFC and OFC differentially regulate dopamine neuron activity, and that the pattern of cortical activation is critical for determining dopamine system output.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

PubMed

Carhart-Harris, Robin L; Erritzoe, David; Williams, Tim; Stone, James M; Reed, Laurence J; Colasanti, Alessandro; Tyacke, Robin J; Leech, Robert; Malizia, Andrea L; Murphy, Kevin; Hobden, Peter; Evans, John; Feilding, Amanda; Wise, Richard G; Nutt, David J

2012-02-07

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

Anterior insula coordinates hierarchical processing of tactile mismatch responses

PubMed Central

Allen, Micah; Fardo, Francesca; Dietz, Martin J.; Hillebrandt, Hauke; Friston, Karl J.; Rees, Geraint; Roepstorff, Andreas

2016-01-01

The body underlies our sense of self, emotion, and agency. Signals arising from the skin convey warmth, social touch, and the physical characteristics of external stimuli. Surprising or unexpected tactile sensations can herald events of motivational salience, including imminent threats (e.g., an insect bite) and hedonic rewards (e.g., a caressing touch). Awareness of such events is thought to depend upon the hierarchical integration of body-related mismatch responses by the anterior insula. To investigate this possibility, we measured brain activity using functional magnetic resonance imaging, while healthy participants performed a roving tactile oddball task. Mass-univariate analysis demonstrated robust activations in limbic, somatosensory, and prefrontal cortical areas previously implicated in tactile deviancy, body awareness, and cognitive control. Dynamic Causal Modelling revealed that unexpected stimuli increased the strength of forward connections along a caudal to rostral hierarchy—projecting from thalamic and somatosensory regions towards insula, cingulate and prefrontal cortices. Within this ascending flow of sensory information, the AIC was the only region to show increased backwards connectivity to the somatosensory cortex, augmenting a reciprocal exchange of neuronal signals. Further, participants who rated stimulus changes as easier to detect showed stronger modulation of descending PFC to AIC connections by deviance. These results suggest that the AIC coordinates hierarchical processing of tactile prediction error. They are interpreted in support of an embodied predictive coding model where AIC mediated body awareness is involved in anchoring a global neuronal workspace. PMID:26584870

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

PubMed

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

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

Interaction of childhood urbanicity and variation in dopamine genes alters adult prefrontal function as measured by functional magnetic resonance imaging (fMRI).

PubMed

Reed, Jessica L; D'Ambrosio, Enrico; Marenco, Stefano; Ursini, Gianluca; Zheutlin, Amanda B; Blasi, Giuseppe; Spencer, Barbara E; Romano, Raffaella; Hochheiser, Jesse; Reifman, Ann; Sturm, Justin; Berman, Karen F; Bertolino, Alessandro; Weinberger, Daniel R; Callicott, Joseph H

2018-01-01

Brain phenotypes showing environmental influence may help clarify unexplained associations between urban exposure and psychiatric risk. Heritable prefrontal fMRI activation during working memory (WM) is such a phenotype. We hypothesized that urban upbringing (childhood urbanicity) would alter this phenotype and interact with dopamine genes that regulate prefrontal function during WM. Further, dopamine has been hypothesized to mediate urban-associated factors like social stress. WM-related prefrontal function was tested for main effects of urbanicity, main effects of three dopamine genes-catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)-and, importantly, dopamine gene-by-urbanicity interactions. For COMT, three independent human samples were recruited (total n = 487). We also studied 253 subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM task was the dependent variable, while childhood urbanicity, dopamine genotype, and urbanicity-dopamine interactions were independent variables. Main effects of dopamine genes and of urbanicity were found. Individuals raised in an urban environment showed altered prefrontal activation relative to those raised in rural or town settings. For each gene, dopamine genotype-by-urbanicity interactions were shown in prefrontal cortex-COMT replicated twice in two independent samples. An urban childhood upbringing altered prefrontal function and interacted with each gene to alter genotype-phenotype relationships. Gene-environment interactions between multiple dopamine genes and urban upbringing suggest that neural effects of developmental environmental exposure could mediate, at least partially, increased risk for psychiatric illness in urban environments via dopamine genes expressed into adulthood.

Extrapunitive and Intropunitive Individuals Activate Different Parts of the Prefrontal Cortex under an Ego-Blocking Frustration

PubMed Central

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

2014-01-01

Different people make different responses when they face a frustrating situation: some punish others (extrapunitive), while others punish themselves (intropunitive). Few studies have investigated the neural structures that differentiate extrapunitive and intropunitive individuals. The present fMRI study explored these neural structures using two different frustrating situations: an ego-blocking situation which blocks a desire or goal, and a superego-blocking situation which blocks self-esteem. In the ego-blocking condition, the extrapunitive group (n = 9) showed greater activation in the bilateral ventrolateral prefrontal cortex, indicating that these individuals prefer emotional processing. On the other hand, the intropunitive group (n = 9) showed greater activation in the left dorsolateral prefrontal cortex, possibly reflecting an effortful control for anger reduction. Such patterns were not observed in the superego-blocking condition. These results indicate that the prefrontal cortex is the source of individual differences in aggression direction in the ego-blocking situation. PMID:24454951

Spatiotemporal dynamics of brain activity during the transition from visually guided to memory-guided force control

PubMed Central

Poon, Cynthia; Chin-Cottongim, Lisa G.; Coombes, Stephen A.; Corcos, Daniel M.

2012-01-01

It is well established that the prefrontal cortex is involved during memory-guided tasks whereas visually guided tasks are controlled in part by a frontal-parietal network. However, the nature of the transition from visually guided to memory-guided force control is not as well established. As such, this study examines the spatiotemporal pattern of brain activity that occurs during the transition from visually guided to memory-guided force control. We measured 128-channel scalp electroencephalography (EEG) in healthy individuals while they performed a grip force task. After visual feedback was removed, the first significant change in event-related activity occurred in the left central region by 300 ms, followed by changes in prefrontal cortex by 400 ms. Low-resolution electromagnetic tomography (LORETA) was used to localize the strongest activity to the left ventral premotor cortex and ventral prefrontal cortex. A second experiment altered visual feedback gain but did not require memory. In contrast to memory-guided force control, altering visual feedback gain did not lead to early changes in the left central and midline prefrontal regions. Decreasing the spatial amplitude of visual feedback did lead to changes in the midline central region by 300 ms, followed by changes in occipital activity by 400 ms. The findings show that subjects rely on sensorimotor memory processes involving left ventral premotor cortex and ventral prefrontal cortex after the immediate transition from visually guided to memory-guided force control. PMID:22696535

Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

PubMed Central

Gilmartin, Marieke R.; Helmstetter, Fred J.

2010-01-01

The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increased activity during the trace interval separating the CS and UCS. We investigated the contribution of prefrontal neural activity in the rat to the acquisition of trace fear conditioning using microinfusions of the γ-aminobutyric acid type A (GABAA) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-d-aspartate (NMDA) receptor-mediated signaling in trace fear conditioning using the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Temporary inactivation of prefrontal activity with muscimol or blockade of NMDA receptor-dependent transmission in mPFC impaired the acquisition of trace, but not delay, conditional fear responses. Simultaneously acquired contextual fear responses were also impaired in drug-treated rats exposed to trace or delay, but not unpaired, training protocols. Our results support the idea that synaptic plasticity within the mPFC is critical for the long-term storage of memory in trace fear conditioning. PMID:20504949

Response repetition biases in human perceptual decisions are explained by activity decay in competitive attractor models

PubMed Central

Bonaiuto, James J; de Berker, Archy; Bestmann, Sven

2016-01-01

Animals and humans have a tendency to repeat recent choices, a phenomenon known as choice hysteresis. The mechanism for this choice bias remains unclear. Using an established, biophysically informed model of a competitive attractor network for decision making, we found that decaying tail activity from the previous trial caused choice hysteresis, especially during difficult trials, and accurately predicted human perceptual choices. In the model, choice variability could be directionally altered through amplification or dampening of post-trial activity decay through simulated depolarizing or hyperpolarizing network stimulation. An analogous intervention using transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (dlPFC) yielded a close match between model predictions and experimental results: net soma depolarizing currents increased choice hysteresis, while hyperpolarizing currents suppressed it. Residual activity in competitive attractor networks within dlPFC may thus give rise to biases in perceptual choices, which can be directionally controlled through non-invasive brain stimulation. DOI: http://dx.doi.org/10.7554/eLife.20047.001 PMID:28005007

Chronic cocaine disrupts mesocortical learning mechanisms

PubMed Central

Buchta, William C.; Riegel, Arthur C.

2016-01-01

The addictive power of drugs of abuse such as cocaine comes from their ability to hijack natural reward and plasticity mechanisms mediated by dopamine signaling in the brain. Reward learning involves burst firing of midbrain dopamine neurons in response to rewards and cues predictive of reward. The resulting release of dopamine in terminal regions is thought to act as a teaching signaling to areas such as the prefrontal cortex and striatum. In this review, we posit that a pool of extrasynaptic dopaminergic D1-like receptors activated in response to dopamine neuron burst firing serve to enable synaptic plasticity in the prefrontal cortex in response to rewards and their cues. We propose that disruptions in these mechanisms following chronic cocaine use contribute to addiction pathology, in part due to the unique architecture of the mesocortical pathway. By blocking dopamine reuptake in the cortex, cocaine elevates dopamine signaling at these extra-synaptic receptors, prolonging D1-receptor activation and the subsequent activation of intracellular signaling cascades, and thus inducing long-lasting maladaptive plasticity. These cellular adaptations may account for many of the changes in cortical function observed in drug addicts, including an enduring vulnerability to relapse. Therefore, understanding and targeting these neuroadaptations may provide cognitive benefits and help prevent relapse in human drug addicts. PMID:25704202

Medial prefrontal cortex activity during the extinction of conditioned fear: an investigation using functional near-infrared spectroscopy.

PubMed

Guhn, Anne; Dresler, Thomas; Hahn, Tim; Mühlberger, Andreas; Ströhle, Andreas; Deckert, Jürgen; Herrmann, Martin J

2012-06-01

The majority of fear conditioning studies in humans have focused on fear acquisition rather than fear extinction. For this reason only a few functional imaging studies on fear extinction are available. A large number of animal studies indicate the medial prefrontal cortex (mPFC) as neuronal substrate of extinction. We therefore determined mPFC contribution during extinction learning after a discriminative fear conditioning in 34 healthy human subjects by using functional near-infrared spectroscopy. During the extinction training, a previously conditioned neutral face (conditioned stimulus, CS+) no longer predicted an aversive scream (unconditioned stimulus, UCS). Considering differential valence and arousal ratings as well as skin conductance responses during the acquisition phase, we found a CS+ related increase in oxygenated haemoglobin concentration changes within the mPFC over the time course of extinction. Late CS+ trials further revealed higher activation than CS- trials in a cluster of probe set channels covering the mPFC. These results are in line with previous findings on extinction and further emphasize the mPFC as significant for associative learning processes. During extinction, the diminished fear association between a former CS+ and a UCS is inversely correlated with mPFC activity--a process presumably dysfunctional in anxiety disorders. Copyright © 2012 S. Karger AG, Basel.

Frames, biases, and rational decision-making in the human brain.

PubMed

De Martino, Benedetto; Kumaran, Dharshan; Seymour, Ben; Dolan, Raymond J

2006-08-04

Human choices are remarkably susceptible to the manner in which options are presented. This so-called "framing effect" represents a striking violation of standard economic accounts of human rationality, although its underlying neurobiology is not understood. We found that the framing effect was specifically associated with amygdala activity, suggesting a key role for an emotional system in mediating decision biases. Moreover, across individuals, orbital and medial prefrontal cortex activity predicted a reduced susceptibility to the framing effect. This finding highlights the importance of incorporating emotional processes within models of human choice and suggests how the brain may modulate the effect of these biasing influences to approximate rationality.

Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)

PubMed Central

Blackman, Rachael K.; Crowe, David A.; DeNicola, Adele L.; Sakellaridi, Sofia; MacDonald, Angus W.

2016-01-01

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia. SIGNIFICANCE STATEMENT Functional imaging studies have demonstrated that cognitive control deficits in schizophrenia are associated with reduced activation of the dorsolateral prefrontal cortex (MacDonald et al., 2005). However, these data do not reveal how the disease has disrupted the function of prefrontal neurons to produce the observed deficits in cognitive control. Relating cognitive control to neurophysiological signals at a cellular level in prefrontal cortex is a necessary first step toward understanding how disruption of these signals could lead to cognitive control failure in neuropsychiatric disease. To that end, we translated a task that measures cognitive control deficits in patients with schizophrenia to monkeys and describe here how neural signals in prefrontal cortex relate to performance. PMID:27053213

A machine learning approach to identify functional biomarkers in human prefrontal cortex for individuals with traumatic brain injury using functional near-infrared spectroscopy.

PubMed

Karamzadeh, Nader; Amyot, Franck; Kenney, Kimbra; Anderson, Afrouz; Chowdhry, Fatima; Dashtestani, Hadis; Wassermann, Eric M; Chernomordik, Victor; Boccara, Claude; Wegman, Edward; Diaz-Arrastia, Ramon; Gandjbakhche, Amir H

2016-11-01

We have explored the potential prefrontal hemodynamic biomarkers to characterize subjects with Traumatic Brain Injury (TBI) by employing the multivariate machine learning approach and introducing a novel task-related hemodynamic response detection followed by a heuristic search for optimum set of hemodynamic features. To achieve this goal, the hemodynamic response from a group of 31 healthy controls and 30 chronic TBI subjects were recorded as they performed a complexity task. To determine the optimum hemodynamic features, we considered 11 features and their combinations in characterizing TBI subjects. We investigated the significance of the features by utilizing a machine learning classification algorithm to score all the possible combinations of features according to their predictive power. The identified optimum feature elements resulted in classification accuracy, sensitivity, and specificity of 85%, 85%, and 84%, respectively. Classification improvement was achieved for TBI subject classification through feature combination. It signified the major advantage of the multivariate analysis over the commonly used univariate analysis suggesting that the features that are individually irrelevant in characterizing the data may become relevant when used in combination. We also conducted a spatio-temporal classification to identify regions within the prefrontal cortex (PFC) that contribute in distinguishing between TBI and healthy subjects. As expected, Brodmann areas (BA) 10 within the PFC were isolated as the region that healthy subjects (unlike subjects with TBI), showed major hemodynamic activity in response to the High Complexity task. Overall, our results indicate that identified temporal and spatio-temporal features from PFC's hemodynamic activity are promising biomarkers in classifying subjects with TBI.

Sex-related differences in neural activity during emotion regulation.

PubMed

Mak, Amanda K Y; Hu, Zhi-guo; Zhang, John X X; Xiao, Zhuangwei; Lee, Tatia M C

2009-11-01

The sex disparity in the development of depression has long been an important research topic, but the sex-related differences in neural activity during emotion regulation have been less thoroughly studied. It was hypothesized that, during the regulation of emotion, there would be more activation in the prefrontal regions implicated in cognitive processing for males, while there would be more activation in the prefrontal regions implicated in affective processing for females. This fMRI study recruited 12 females and 12 males who were required to view or to regulate the negative and positive emotion induced by some emotion-arousing pictures. During the regulation of negative emotion, both males and females had stronger activation in the left anterior cingulate gyrus, but males showed more activation in the prefrontal regions in general, including the left dorsolateral and lateral orbitofrontal gyrus as well as the right anterior cingulate gyrus, while females only showed stronger activation in the left medial orbitofrontal gyrus. For the regulation of positive emotion, both males and females showed stronger activation in the left dorsomedial prefrontal gyrus, but males were found to also have stronger activity in the left lateral orbitofrontal gyrus. It was concluded that there are common as well as sex-specific sets of brain regions involved in regulating negative and positive emotion, and the findings may have significant implications for females' vulnerability to developing depression.

Frontal Theta Links Prediction Errors to Behavioral Adaptation in Reinforcement Learning

PubMed Central

Cavanagh, James F.; Frank, Michael J.; Klein, Theresa J.; Allen, John J.B.

2009-01-01

Investigations into action monitoring have consistently detailed a fronto-central voltage deflection in the Event-Related Potential (ERP) following the presentation of negatively valenced feedback, sometimes termed the Feedback Related Negativity (FRN). The FRN has been proposed to reflect a neural response to prediction errors during reinforcement learning, yet the single trial relationship between neural activity and the quanta of expectation violation remains untested. Although ERP methods are not well suited to single trial analyses, the FRN has been associated with theta band oscillatory perturbations in the medial prefrontal cortex. Medio-frontal theta oscillations have been previously associated with expectation violation and behavioral adaptation and are well suited to single trial analysis. Here, we recorded EEG activity during a probabilistic reinforcement learning task and fit the performance data to an abstract computational model (Q-learning) for calculation of single-trial reward prediction errors. Single-trial theta oscillatory activities following feedback were investigated within the context of expectation (prediction error) and adaptation (subsequent reaction time change). Results indicate that interactive medial and lateral frontal theta activities reflect the degree of negative and positive reward prediction error in the service of behavioral adaptation. These different brain areas use prediction error calculations for different behavioral adaptations: with medial frontal theta reflecting the utilization of prediction errors for reaction time slowing (specifically following errors), but lateral frontal theta reflecting prediction errors leading to working memory-related reaction time speeding for the correct choice. PMID:19969093

A three-layered model of primate prefrontal cortex encodes identity and abstract categorical structure of behavioral sequences.

PubMed

Hinaut, Xavier; Dominey, Peter Ford

2011-01-01

Categorical encoding is crucial for mastering large bodies of related sensory-motor experiences, but what is its neural substrate? In an effort to respond to this question, recent single-unit recording studies in the macaque lateral prefrontal cortex (LPFC) have demonstrated two characteristic forms of neural encoding of the sequential structure of the animal's sensory-motor experience. One population of neurons encodes the specific behavioral sequences. A second population of neurons encodes the sequence category (e.g. ABAB, AABB or AAAA) and does not differentiate sequences within the category (Shima, K., Isoda, M., Mushiake, H., Tanji, J., 2007. Categorization of behavioural sequences in the prefrontal cortex. Nature 445, 315-318.). Interestingly these neurons are intermingled in the lateral prefrontal cortex, and not topographically segregated. Thus, LPFC may provide a neurophysiological basis for sensorimotor categorization. Here we report on a neural network simulation study that reproduces and explains these results. We model a cortical circuit composed of three layers (infragranular, granular, and supragranular) of 5*5 leaky integrator neurons with a sigmoidal output function, and we examine 1000 such circuits running in parallel. Crucially the three layers are interconnected with recurrent connections, thus producing a dynamical system that is inherently sensitive to the spatiotemporal structure of the sequential inputs. The model is presented with 11 four-element sequences following Shima et al. We isolated one subpopulation of neurons each of whose activity predicts individual sequences, and a second population that predicts category independent of the specific sequence. We argue that a richly interconnected cortical circuit is capable of internally generating a neural representation of category membership, thus significantly extending the scope of recurrent network computation. In order to demonstrate that these representations can be used to create an explicit categorization capability, we introduced an additional neural structure corresponding to the striatum. We showed that via cortico-striatal plasticity, neurons in the striatum could produce an explicit representation both of the identity of each sequence, and its category membership. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neuroelectrical imaging investigation of cortical activity during listening to music in prelingually deaf children with cochlear implants.

PubMed

Marsella, Pasquale; Scorpecci, Alessandro; Vecchiato, Giovanni; Maglione, Anton Giulio; Colosimo, Alfredo; Babiloni, Fabio

2014-05-01

To date, no objective measure of the pleasantness of music perception by children with cochlear implants has been reported. The EEG alpha asymmetries of pre-frontal cortex activation are known to relate to emotional/affective engagement in a perceived stimulus. More specifically, according to the "withdrawal/approach" model, an unbalanced de-synchronization of the alpha activity in the left prefrontal cortex has been associated with a positive affective state/approach toward a stimulus, and an unbalanced de-synchronization of the same activity in the right prefrontal cortex with a negative affective state/withdrawal from a stimulus. In the present study, High-Resolution EEG with Source Reconstruction was used to compare the music-induced alpha asymmetries of the prefrontal cortex in a group of prelingually deaf implanted children and in a control group of normal-hearing children. Six normal-hearing and six age-matched deaf children using a unilateral cochlear implants underwent High-Resolution EEG recordings as they were listening to a musical cartoon. Musical stimuli were delivered in three versions: Normal, Distort (reverse audio flow) and Mute. The EEG alpha rhythm asymmetry was analyzed: Power Spectral Density was calculated for each Region of Interest, together with a right-left imbalance index. A map of cortical activation was then reconstructed on a realistic cortical model. Asymmetries of EEG alpha rhythm in the prefrontal cortices were observed in both groups. In the normal-hearing children, the asymmetries were consistent with the withdrawal/approach model, whereas in cochlear implant users they were not. Moreover, in implanted children a different pattern of alpha asymmetries in extrafrontal cortical areas was noticed as compared to normal-hearing subjects. The peculiar pattern of alpha asymmetries in implanted children's prefrontal cortex in response to musical stimuli suggests an inability by these subjects to discriminate normal from dissonant music and to appreciate the pleasantness of normal music. High-Resolution EEG may prove to be a promising tool for objectively measuring prefrontal cortex alpha asymmetries in child cochlear implant users. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Dynamic Interaction between Reinforcement Learning and Attention in Multidimensional Environments.

PubMed

Leong, Yuan Chang; Radulescu, Angela; Daniel, Reka; DeWoskin, Vivian; Niv, Yael

2017-01-18

Little is known about the relationship between attention and learning during decision making. Using eye tracking and multivariate pattern analysis of fMRI data, we measured participants' dimensional attention as they performed a trial-and-error learning task in which only one of three stimulus dimensions was relevant for reward at any given time. Analysis of participants' choices revealed that attention biased both value computation during choice and value update during learning. Value signals in the ventromedial prefrontal cortex and prediction errors in the striatum were similarly biased by attention. In turn, participants' focus of attention was dynamically modulated by ongoing learning. Attentional switches across dimensions correlated with activity in a frontoparietal attention network, which showed enhanced connectivity with the ventromedial prefrontal cortex between switches. Our results suggest a bidirectional interaction between attention and learning: attention constrains learning to relevant dimensions of the environment, while we learn what to attend to via trial and error. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms of rule acquisition and rule following in inductive reasoning.

PubMed

Crescentini, Cristiano; Seyed-Allaei, Shima; De Pisapia, Nicola; Jovicich, Jorge; Amati, Daniele; Shallice, Tim

2011-05-25

Despite the recent interest in the neuroanatomy of inductive reasoning processes, the regional specificity within prefrontal cortex (PFC) for the different mechanisms involved in induction tasks remains to be determined. In this study, we used fMRI to investigate the contribution of PFC regions to rule acquisition (rule search and rule discovery) and rule following. Twenty-six healthy young adult participants were presented with a series of images of cards, each consisting of a set of circles numbered in sequence with one colored blue. Participants had to predict the position of the blue circle on the next card. The rules that had to be acquired pertained to the relationship among succeeding stimuli. Responses given by subjects were categorized in a series of phases either tapping rule acquisition (responses given up to and including rule discovery) or rule following (correct responses after rule acquisition). Mid-dorsolateral PFC (mid-DLPFC) was active during rule search and remained active until successful rule acquisition. By contrast, rule following was associated with activation in temporal, motor, and medial/anterior prefrontal cortex. Moreover, frontopolar cortex (FPC) was active throughout the rule acquisition and rule following phases before a rule became familiar. We attributed activation in mid-DLPFC to hypothesis generation and in FPC to integration of multiple separate inferences. The present study provides evidence that brain activation during inductive reasoning involves a complex network of frontal processes and that different subregions respond during rule acquisition and rule following phases.

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

PubMed

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

2005-11-07

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

Lucid Dreaming and Ventromedial versus Dorsolateral Prefrontal Task Performance

PubMed Central

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

2010-01-01

Activity in the prefrontal cortex may distinguish the meta-awareness experienced during lucid dreams from its absence in normal dreams. To examine a possible relationship between dream lucidity and prefrontal task performance, we carried out a prospective study in 28 high school students. Participants performed the Wisconsin Card Sort and Iowa Gambling tasks, then for one week kept dream journals and reported sleep quality and lucidity-related dream characteristics. Participants who exhibited a greater degree of lucidity performed significantly better on the task that engages the ventromedial prefrontal cortex (the Iowa Gambling Task), but degree of lucidity achieved did not distinguish performance on the task that engages the dorsolateral prefrontal cortex (the Wisconsin Card Sort Task), nor did it distinguish self-reported sleep quality or baseline characteristics. The association between performance on the Iowa Gambling Task and lucidity suggests a connection between lucid dreaming and ventromedial prefrontal function. PMID:20829072

Neural mechanisms tracking popularity in real-world social networks.

PubMed

Zerubavel, Noam; Bearman, Peter S; Weber, Jochen; Ochsner, Kevin N

2015-12-08

Differences in popularity are a key aspect of status in virtually all human groups and shape social interactions within them. Little is known, however, about how we track and neurally represent others' popularity. We addressed this question in two real-world social networks using sociometric methods to quantify popularity. Each group member (perceiver) viewed faces of every other group member (target) while whole-brain functional MRI data were collected. Independent functional localizer tasks were used to identify brain systems supporting affective valuation (ventromedial prefrontal cortex, ventral striatum, amygdala) and social cognition (dorsomedial prefrontal cortex, precuneus, temporoparietal junction), respectively. During the face-viewing task, activity in both types of neural systems tracked targets' sociometric popularity, even when controlling for potential confounds. The target popularity-social cognition system relationship was mediated by valuation system activity, suggesting that observing popular individuals elicits value signals that facilitate understanding their mental states. The target popularity-valuation system relationship was strongest for popular perceivers, suggesting enhanced sensitivity to differences among other group members' popularity. Popular group members also demonstrated greater interpersonal sensitivity by more accurately predicting how their own personalities were perceived by other individuals in the social network. These data offer insights into the mechanisms by which status guides social behavior.

Self-esteem Modulates Medial Prefrontal Cortical Responses to Evaluative Social Feedback

PubMed Central

Kelley, William M.; Heatherton, Todd F.

2010-01-01

Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing. PMID:20351022

Prefrontal cortex activity during response selection predicts processing speed impairment in schizophrenia

PubMed Central

Woodward, Neil D.; Duffy-Alberto, Brittney; Karbasforoushan, Haleh

2014-01-01

Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and indentifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. 26 patients with schizophrenia and 21 healthy subjects underwent fMRI scanning during performance of 2 and 4-choice-reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between 2 and 4-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia. PMID:23816240

Neural correlates of autobiographical memory retrieval in children and adults.

PubMed

Bauer, Patricia J; Pathman, Thanujeni; Inman, Cory; Campanella, Carolina; Hamann, Stephan

2017-04-01

Autobiographical memory (AM) is a critically important form of memory for life events that undergoes substantial developmental changes from childhood to adulthood. Relatively little is known regarding the functional neural correlates of AM retrieval in children as assessed with fMRI, and how they may differ from adults. We investigated this question with 14 children ages 8-11 years and 14 adults ages 19-30 years, contrasting AM retrieval with semantic memory (SM) retrieval. During scanning, participants were cued by verbal prompts to retrieve previously selected recent AMs or to verify semantic properties of words. As predicted, both groups showed AM retrieval-related increased activation in regions implicated in prior studies, including bilateral hippocampus, and prefrontal, posterior cingulate, and parietal cortices. Adults showed greater activation in the hippocampal/parahippocampal region as well as prefrontal and parietal cortex, relative to children; age-related differences were most prominent in the first 8 sec versus the second 8 sec of AM retrieval and when AM retrieval was contrasted with semantic retrieval. This study is the first to characterise similarities and differences during AM retrieval in children and adults using fMRI.

Changes in the neural bases of emotion regulation associated with clinical improvement in children with behavior problems.

PubMed

Lewis, Marc D; Granic, Isabela; Lamm, Connie; Zelazo, Philip David; Stieben, Jim; Todd, Rebecca M; Moadab, Ida; Pepler, Debra

2008-01-01

Children's behavior problems may stem from ineffective cortical mechanisms for regulating negative emotions, and the success of interventions may depend on their impact on such mechanisms. We examined neurophysiological markers associated with emotion regulation in children comorbid for externalizing and internalizing problems before and after treatment. We hypothesized that treatment success would correspond with reduced ventral prefrontal activation, and increased dorsomedial prefrontal activation, at the time point of an event-related potential (ERP) associated with inhibitory control. Twenty-seven 8- to 12-year-old children (with usable data) were tested before and after a 14-week community-based treatment program and assessed as to improvement status. Fifteen 8- to 12-year-olds from the normal population (with usable data) were tested over the same interval. All children completed an emotion-induction go/no-go task while fitted with a 128-channel electrode net at each test session. ERP amplitudes, and estimates of cortical activation in prefrontal regions of interest, were measured at the peak of the "inhibitory" N2 and compared between improvers, nonimprovers, and nonclinical children. ERP amplitudes showed no group differences. However, improvers showed an overall reduction in ventral prefrontal activation from pretreatment to posttreatment, bringing them in line with nonclinical children, whereas ventral activation remained high for nonimprovers. Both improvers and nonimprovers showed high dorsal activation relative to nonclinical children. Supplementary analyses indicated that only ventral prefrontal regions, and only within the N2 time window, showed decreased activity from pre- to posttreatment, suggesting changes in regulatory processes rather than in overall emotional arousal. These cortically mediated changes may permit a reduction in the overengaged, rigid style of emotion regulation characteristic of children with behavior problems.

Stimulant Medication and Prefrontal Functional Connectivity during Working Memory in ADHD: A Preliminary Report

ERIC Educational Resources Information Center

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

2010-01-01

Objective: Recent theoretical and empirical work suggests that while unmedicated, children with ADHD have a deficit in subcortical processing that leads to greater and more varied prefrontal cortical (PFC) activation, compared to (a) age-matched control participants and (b) their own brain activity while on stimulant medication. This pattern has…

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…

Neural and computational processes underlying dynamic changes in self-esteem

PubMed Central

Rutledge, Robb B; Moutoussis, Michael; Dolan, Raymond J

2017-01-01

Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an ‘interpersonal vulnerability’ dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability. PMID:29061228

Neural and computational processes underlying dynamic changes in self-esteem.

PubMed

Will, Geert-Jan; Rutledge, Robb B; Moutoussis, Michael; Dolan, Raymond J

2017-10-24

Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an 'interpersonal vulnerability' dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability.

An integrative theory of prefrontal cortex function.

PubMed

Miller, E K; Cohen, J D

2001-01-01

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

NR2A-Containing NMDARs in the Prefrontal Cortex Are Required for Working Memory and Associated with Age-Related Cognitive Decline.

PubMed

McQuail, Joseph A; Beas, B Sofia; Kelly, Kyle B; Simpson, Kailey L; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

2016-12-14

Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory. Experiments herein show that working memory depends on NR2A- but not NR2B-NMDARs in PFC of rats and that NR2A-NMDARs mediate the majority of evoked NMDAR currents on layer 2/3 PFC pyramidal neurons. Moreover, attenuated expression of the NR2A but not the NR2B subunit in PFC associates with naturally occurring working memory impairment in aged rats. Finally, NMDAR currents and working memory are enhanced in aged rats by promoting activation of the NR2A-enriched synaptic pool of PFC NMDARs. These results implicate NR2A-NMDARs in normal working memory and suggest novel treatment strategies for improving working memory in cognitive disorders. Working memory, the ability to hold information "in mind," requires persistent activity of pyramidal neurons in prefrontal cortex (PFC) mediated by NMDA receptor (NMDAR) activation. NMDAR loss in PFC may account for working memory impairments in aging and psychiatric disease. Our studies demonstrate that NMDARs containing the NR2A subunit, but not the NR2B subunit, are required for working memory and that loss of NR2A predicts severity of age-related working memory impairment. The importance of NR2A to working memory is likely due its abundant contribution to pyramidal neuron activity and location at synaptic sites in PFC. This information is useful in designing new therapies to treat working memory impairments by enhancing the function of NR2A-containing NMDARs. Copyright © 2016 the authors 0270-6474/16/3612537-12$15.00/0.

Someone has to give in: theta oscillations correlate with adaptive behavior in social bargaining.

PubMed

Billeke, Pablo; Zamorano, Francisco; López, Tamara; Rodriguez, Carlos; Cosmelli, Diego; Aboitiz, Francisco

2014-12-01

During social bargain, one has to both figure out the others' intentions and behave strategically in such a way that the others' behaviors will be consistent with one's expectations. To understand the neurobiological mechanisms underlying these behaviors, we used electroencephalography while subjects played as proposers in a repeated ultimatum game. We found that subjects adapted their offers to obtain more acceptances in the last round and that this adaptation correlated negatively with prefrontal theta oscillations. People with higher prefrontal theta activity related to a rejection did not adapt their offers along the game to maximize their earning. Moreover, between-subject variation in posterior theta oscillations correlated positively with how individual theta activity influenced the change of offer after a rejection, reflecting a process of behavioral adaptation to the others' demands. Interestingly, people adapted better their offers when they knew that they where playing against a computer, although the behavioral adaptation did not correlate with prefrontal theta oscillation. Behavioral changes between human and computer games correlated with prefrontal theta activity, suggesting that low adaptation in human games could be a strategy. Taken together, these results provide evidence for specific roles of prefrontal and posterior theta oscillations in social bargaining. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2014-09-05

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

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

PubMed

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

2015-10-01

Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change

PubMed Central

Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W.; Savic, Aleksandar; Yang, Genevieve J.; Repovs, Grega; Murray, John D.; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H.

2015-01-01

Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for “hypoconnectivity.” At the whole-brain level, we observed “hyperconnectivity” around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. PMID:25568120

Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change.

PubMed

Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W; Savic, Aleksandar; Yang, Genevieve J; Repovs, Grega; Murray, John D; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H; Gong, Qiyong

2015-01-07

Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for "hypoconnectivity." At the whole-brain level, we observed "hyperconnectivity" around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. Copyright © 2015 the authors 0270-6474/15/350267-20$15.00/0.

Efficient learning mechanisms hold in the social domain and are implemented in the medial prefrontal cortex.

PubMed

Seid-Fatemi, Azade; Tobler, Philippe N

2015-05-01

When we are learning to associate novel cues with outcomes, learning is more efficient if we take advantage of previously learned associations and thereby avoid redundant learning. The blocking effect represents this sort of efficiency mechanism and refers to the phenomenon in which a novel stimulus is blocked from learning when it is associated with a fully predicted outcome. Although there is sufficient evidence that this effect manifests itself when individuals learn about their own rewards, it remains unclear whether it also does when they learn about others' rewards. We employed behavioral and neuroimaging methods to address this question. We demonstrate that blocking does indeed occur in the social domain and it does so to a similar degree as observed in the individual domain. On the neural level, activations in the medial prefrontal cortex (mPFC) show a specific contribution to blocking and learning-related prediction errors in the social domain. These findings suggest that the efficiency principle that applies to reward learning in the individual domain also applies to that in the social domain, with the mPFC playing a central role in implementing it. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Prefrontal Contribution to Decision-Making under Free-Choice Conditions

PubMed Central

Funahashi, Shintaro

2017-01-01

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

Neural substrates of updating the prediction through prediction error during decision making.

PubMed

Wang, Ying; Ma, Ning; He, Xiaosong; Li, Nan; Wei, Zhengde; Yang, Lizhuang; Zha, Rujing; Han, Long; Li, Xiaoming; Zhang, Daren; Liu, Ying; Zhang, Xiaochu

2017-08-15

Learning of prediction error (PE), including reward PE and risk PE, is crucial for updating the prediction in reinforcement learning (RL). Neurobiological and computational models of RL have reported extensive brain activations related to PE. However, the occurrence of PE does not necessarily predict updating the prediction, e.g., in a probability-known event. Therefore, the brain regions specifically engaged in updating the prediction remain unknown. Here, we conducted two functional magnetic resonance imaging (fMRI) experiments, the probability-unknown Iowa Gambling Task (IGT) and the probability-known risk decision task (RDT). Behavioral analyses confirmed that PEs occurred in both tasks but were only used for updating the prediction in the IGT. By comparing PE-related brain activations between the two tasks, we found that the rostral anterior cingulate cortex/ventral medial prefrontal cortex (rACC/vmPFC) and the posterior cingulate cortex (PCC) activated only during the IGT and were related to both reward and risk PE. Moreover, the responses in the rACC/vmPFC and the PCC were modulated by uncertainty and were associated with reward prediction-related brain regions. Electric brain stimulation over these regions lowered the performance in the IGT but not in the RDT. Our findings of a distributed neural circuit of PE processing suggest that the rACC/vmPFC and the PCC play a key role in updating the prediction through PE processing during decision making. Copyright © 2017 Elsevier Inc. All rights reserved.

Disrupted prediction errors index social deficits in autism spectrum disorder

PubMed Central

Balsters, Joshua H; Apps, Matthew A J; Bolis, Dimitris; Lehner, Rea; Gallagher, Louise; Wenderoth, Nicole

2017-01-01

Abstract Social deficits are a core symptom of autism spectrum disorder; however, the perturbed neural mechanisms underpinning these deficits remain unclear. It has been suggested that social prediction errors—coding discrepancies between the predicted and actual outcome of another’s decisions—might play a crucial role in processing social information. While the gyral surface of the anterior cingulate cortex signalled social prediction errors in typically developing individuals, this crucial social signal was altered in individuals with autism spectrum disorder. Importantly, the degree to which social prediction error signalling was aberrant correlated with diagnostic measures of social deficits. Effective connectivity analyses further revealed that, in typically developing individuals but not in autism spectrum disorder, the magnitude of social prediction errors was driven by input from the ventromedial prefrontal cortex. These data provide a novel insight into the neural substrates underlying autism spectrum disorder social symptom severity, and further research into the gyral surface of the anterior cingulate cortex and ventromedial prefrontal cortex could provide more targeted therapies to help ameliorate social deficits in autism spectrum disorder. PMID:28031223

A General Role for Medial Prefrontal Cortex in Event Prediction

DTIC Science & Technology

2014-07-11

anterior cingulate cortex modulates attentional response: combined fMRI and ERP evidence. J. Cogn . Neurosci . 18, 766–780. doi: 10.1162/jocn.2006.18.5.766...losses in the anterior cingulate cortex. Cogn . Affect. Behav. Neurosci . 7, 327–336. doi: 10.3758/cabn.7.4.327 Shima, K., and Tanji, J. (1998). Role of...COMPUTATIONAL NEUROSCIENCE ORIGINAL RESEARCH ARTICLE published: 11 July 2014 doi: 10.3389/fncom.2014.00069 A general role for medial prefrontal

Neural activity during affect labeling predicts expressive writing effects on well-being: GLM and SVM approaches.

PubMed

Memarian, Negar; Torre, Jared B; Haltom, Kate E; Stanton, Annette L; Lieberman, Matthew D

2017-09-01

Affect labeling (putting feelings into words) is a form of incidental emotion regulation that could underpin some benefits of expressive writing (i.e. writing about negative experiences). Here, we show that neural responses during affect labeling predicted changes in psychological and physical well-being outcome measures 3 months later. Furthermore, neural activity of specific frontal regions and amygdala predicted those outcomes as a function of expressive writing. Using supervised learning (support vector machines regression), improvements in four measures of psychological and physical health (physical symptoms, depression, anxiety and life satisfaction) after an expressive writing intervention were predicted with an average of 0.85% prediction error [root mean square error (RMSE) %]. The predictions were significantly more accurate with machine learning than with the conventional generalized linear model method (average RMSE: 1.3%). Consistent with affect labeling research, right ventrolateral prefrontal cortex (RVLPFC) and amygdalae were top predictors of improvement in the four outcomes. Moreover, RVLPFC and left amygdala predicted benefits due to expressive writing in satisfaction with life and depression outcome measures, respectively. This study demonstrates the substantial merit of supervised machine learning for real-world outcome prediction in social and affective neuroscience. © The Author (2017). Published by Oxford University Press.

Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study

PubMed Central

Altshuler, Lori; Bookheimer, Susan; Townsend, Jennifer; Proenza, Manuel A; Sabb, Fred; Mintz, Jim; Cohen, Mark S

2011-01-01

Objective To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Methods Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis. Results Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant. Conclusions Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder. PMID:18837865

Understanding Human Original Actions Directed at Real-World Goals: The Role of the Lateral Prefrontal Cortex

PubMed Central

Sitnikova, Tatiana; Rosen, Bruce R.; Lord, Louis-David; West, W. Caroline

2014-01-01

Adaptive, original actions, which can succeed in multiple contextual situations, require understanding of what is relevant to a goal. Recognizing what is relevant may also help in predicting kinematics of observed, original actions. During action observation, comparisons between sensory input and expected action kinematics have been argued critical to accurate goal inference. Experimental studies with laboratory tasks, both in humans and nonhuman primates, demonstrated that the lateral prefrontal cortex (LPFC) can learn, hierarchically organize, and use goal-relevant information. To determine whether this LPFC capacity is generalizable to real-world cognition, we recorded functional magnetic resonance imaging (fMRI) data in the human brain during comprehension of original and usual object-directed actions embedded in video-depictions of real-life behaviors. We hypothesized that LPFC will contribute to forming goal-relevant representations necessary for kinematic predictions of original actions. Additionally, resting-state fMRI was employed to examine functional connectivity between the brain regions delineated in the video fMRI experiment. According to behavioral data, original videos could be understood by identifying elements relevant to real-life goals at different levels of abstraction. Patterns of enhanced activity in four regions in the left LPFC, evoked by original, relative to usual, video scenes, were consistent with previous neuroimaging findings on representing abstract and concrete stimuli dimensions relevant to laboratory goals. In the anterior left LPFC, the activity increased selectively when representations of broad classes of objects and actions, which could achieve the perceived overall behavioral goal, were likely to bias kinematic predictions of original actions. In contrast, in the more posterior regions, the activity increased even when concrete properties of the target object were more likely to bias the kinematic prediction. Functional connectivity was observed between contiguous regions along the rostro-caudal LPFC axis, but not between the regions that were not immediately adjacent. These findings generalize the representational hierarchy account of LPFC function to diverse core principles that can govern both production and comprehension of flexible real-life behavior. PMID:25224997

Neural response to pictorial health warning labels can predict smoking behavioral change

PubMed Central

Riddle, Philip J.; Newman-Norlund, Roger D.; Baer, Jessica; Thrasher, James F.

2016-01-01

In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants’ self-reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals’ intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). PMID:27405615

Neural response to pictorial health warning labels can predict smoking behavioral change.

PubMed

Riddle, Philip J; Newman-Norlund, Roger D; Baer, Jessica; Thrasher, James F

2016-11-01

In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants' self-reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals' intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). © The Author (2016). Published by Oxford University Press.

Altered neural activity and emotions following right middle cerebral artery stroke.

PubMed

Paradiso, Sergio; Anderson, Beth M; Boles Ponto, Laura L; Tranel, Daniel; Robinson, Robert G

2011-01-01

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims. Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Correlations between prefrontal neurons form a small-world network that optimizes the generation of multineuron sequences of activity

PubMed Central

Luongo, Francisco J.; Zimmerman, Chris A.; Horn, Meryl E.

2016-01-01

Sequential patterns of prefrontal activity are believed to mediate important behaviors, e.g., working memory, but it remains unclear exactly how they are generated. In accordance with previous studies of cortical circuits, we found that prefrontal microcircuits in young adult mice spontaneously generate many more stereotyped sequences of activity than expected by chance. However, the key question of whether these sequences depend on a specific functional organization within the cortical microcircuit, or emerge simply as a by-product of random interactions between neurons, remains unanswered. We observed that correlations between prefrontal neurons do follow a specific functional organization—they have a small-world topology. However, until now it has not been possible to directly link small-world topologies to specific circuit functions, e.g., sequence generation. Therefore, we developed a novel analysis to address this issue. Specifically, we constructed surrogate data sets that have identical levels of network activity at every point in time but nevertheless represent various network topologies. We call this method shuffling activity to rearrange correlations (SHARC). We found that only surrogate data sets based on the actual small-world functional organization of prefrontal microcircuits were able to reproduce the levels of sequences observed in actual data. As expected, small-world data sets contained many more sequences than surrogate data sets with randomly arranged correlations. Surprisingly, small-world data sets also outperformed data sets in which correlations were maximally clustered. Thus the small-world functional organization of cortical microcircuits, which effectively balances the random and maximally clustered regimes, is optimal for producing stereotyped sequential patterns of activity. PMID:26888108

Affective context interferes with cognitive control in unipolar depression: An fMRI investigation

PubMed Central

Dichter, Gabriel S.; Felder, Jennifer N.; Smoski, Moria J.

2009-01-01

Background Unipolar major depressive disorder (MDD) is characterized by aberrant amygdala responses to sad stimuli and poor cognitive control, but the interactive effects of these impairments are poorly understood. Aim To evaluate brain activation in MDD in response to cognitive control stimuli embedded within sad and neutral contexts. Method Fourteen adults with MDD and fifteen matched controls participated in a mixed block/event-related functional magnetic resonance imaging (fMRI) task that presented oddball target stimuli embedded within blocks of sad or neutral images. Results Target events activated similar prefrontal brain regions in both groups. However, responses to target events embedded within blocks of emotional images revealed a clear group dissociation. During neutral blocks, the control group demonstrated greater activation to targets in the midfrontal gyrus and anterior cingulate relative to the MDD group, replicating previous findings of prefrontal hypo-activation in MDD samples to cognitive control stimuli. However, during sad blocks, the MDD group demonstrated greater activation in a number of prefrontal regions, including the mid-, inferior, and orbito-frontal gyri and the anterior cingulate, suggesting that relatively more prefrontal brain activation was required to disengage from the sad images to respond to the target events. Limitations A larger sample size would have provided greater statistical power, and more standardized stimuli would have increased external validity. Conclusions This double dissociation of prefrontal responses to target events embedded within neutral and sad context suggests that MDD impacts not only responses to affective events, but extends to other cognitive processes carried out in the context of affective engagement. This implies that emotional reactivity to sad events in MDD may impact functioning more broadly than previously understood. PMID:18706701

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

PubMed

Szabó, Ádám György; Farkas, Kinga; Marosi, Csilla; Kozák, Lajos R; Rudas, Gábor; Réthelyi, János; Csukly, Gábor

2017-12-08

Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making.

PubMed

Kohno, Milky; Nurmi, Erika L; Laughlin, Christopher P; Morales, Angelica M; Gail, Emma H; Hellemann, Gerhard S; London, Edythe D

2016-02-01

Brain imaging has revealed links between prefrontal activity during risky decision-making and striatal dopamine receptors. Specifically, striatal dopamine D2-like receptor availability is correlated with risk-taking behavior and sensitivity of prefrontal activation to risk in the Balloon Analogue Risk Task (BART). The extent to which these associations, involving a single neurochemical measure, reflect more general effects of dopaminergic functioning on risky decision making, however, is unknown. Here, 65 healthy participants provided genotypes and performed the BART during functional magnetic resonance imaging. For each participant, dopamine function was assessed using a gene composite score combining known functional variation across five genes involved in dopaminergic signaling: DRD2, DRD3, DRD4, DAT1, and COMT. The gene composite score was negatively related to dorsolateral prefrontal cortical function during risky decision making, and nonlinearly related to earnings on the task. Iterative permutations of all possible allelic variations (7777 allelic combinations) was tested on brain function in an independently defined region of the prefrontal cortex and confirmed empirical validity of the composite score, which yielded stronger association than 95% of all other possible combinations. The gene composite score also accounted for a greater proportion of variability in neural and behavioral measures than the independent effects of each gene variant, indicating that the combined effects of functional dopamine pathway genes can provide a robust assessment, presumably reflecting the cumulative and potentially interactive effects on brain function. Our findings support the view that the links between dopaminergic signaling, prefrontal function, and decision making vary as a function of dopamine signaling capacity.

Spatial Learning and Action Planning in a Prefrontal Cortical Network Model

PubMed Central

Martinet, Louis-Emmanuel; Sheynikhovich, Denis; Benchenane, Karim; Arleo, Angelo

2011-01-01

The interplay between hippocampus and prefrontal cortex (PFC) is fundamental to spatial cognition. Complementing hippocampal place coding, prefrontal representations provide more abstract and hierarchically organized memories suitable for decision making. We model a prefrontal network mediating distributed information processing for spatial learning and action planning. Specific connectivity and synaptic adaptation principles shape the recurrent dynamics of the network arranged in cortical minicolumns. We show how the PFC columnar organization is suitable for learning sparse topological-metrical representations from redundant hippocampal inputs. The recurrent nature of the network supports multilevel spatial processing, allowing structural features of the environment to be encoded. An activation diffusion mechanism spreads the neural activity through the column population leading to trajectory planning. The model provides a functional framework for interpreting the activity of PFC neurons recorded during navigation tasks. We illustrate the link from single unit activity to behavioral responses. The results suggest plausible neural mechanisms subserving the cognitive “insight” capability originally attributed to rodents by Tolman & Honzik. Our time course analysis of neural responses shows how the interaction between hippocampus and PFC can yield the encoding of manifold information pertinent to spatial planning, including prospective coding and distance-to-goal correlates. PMID:21625569

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.

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

PubMed

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

2012-10-01

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

Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice.

PubMed

Pham, T H; Mendez-David, I; Defaix, C; Guiard, B P; Tritschler, L; David, D J; Gardier, A M

2017-01-01

Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain serotonergic system in the AD-like activity of an acute sub-anaesthetic ketamine dose. We compared ketamine and fluoxetine responses in several behavioral tests currently used to predict anxiolytic/antidepressant-like potential in rodents. We also measured their effects on extracellular serotonin levels [5-HT] ext in the medial prefrontal cortex (mPFCx) and brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus involved in emotional behavior, and on 5-HT cell firing in the DRN in highly anxious BALB/cJ mice. Ketamine (10 mg/kg i.p.) had no anxiolytic-like effect, but displayed a long lasting AD-like activity, i.e., 24 h post-administration, compared to fluoxetine (18 mg/kg i.p.). Ketamine (144%) and fluoxetine (171%) increased mPFCx [5-HT] ext compared to vehicle. Ketamine-induced AD-like effect was abolished by a tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA) pointing out the role of the 5-HT system in its behavioral activity. Interestingly, increase in cortical [5-HT] ext following intra-mPFCx ketamine bilateral injection (0.25 μg/side) was correlated with its AD-like activity as measured on swimming duration in the FST in the same mice. Furthermore, pre-treatment with a selective AMPA receptor antagonist (intra-DRN NBQX) blunted the effects of intra-mPFCx ketamine on both the swimming duration in the FST and mPFCx [5-HT] ext suggesting that the AD-like activity of ketamine required activation of DRN AMPA receptors and recruited the prefrontal cortex/brainstem DRN neural circuit in BALB/c mice. These results confirm a key role of cortical 5-HT release in ketamine's AD-like activity following the blockade of glutamatergic NMDA receptors. Tight interactions between mPFCx glutamatergic and serotonergic systems may explain the differences in this activity between ketamine and fluoxetine in vivo. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Copyright © 2016. Published by Elsevier Ltd.

Frontal Preparatory Neural Oscillations Associated with Cognitive Control: A Developmental Study Comparing Young Adults and Adolescents

PubMed Central

Hwang, Kai; Ghuman, Avniel S.; Manoach, Dara S.; Jones, Stephanie R.; Luna, Beatriz

2016-01-01

Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials – AS) compared to preparing to generate a more automatic saccade (prosaccade trials – PS). We found that for adults, AS were associated with increased beta-band (16–38 Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10–18 Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10–26 Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in prefrontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes. PMID:27173759

Metabolomics identifies perturbations in amino acid metabolism in the prefrontal cortex of the learned helplessness rat model of depression.

PubMed

Zhou, Xinyu; Liu, Lanxiang; Zhang, Yuqing; Pu, Juncai; Yang, Lining; Zhou, Chanjuan; Yuan, Shuai; Zhang, Hanping; Xie, Peng

2017-02-20

Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neuroadaptive technology enables implicit cursor control based on medial prefrontal cortex activity.

PubMed

Zander, Thorsten O; Krol, Laurens R; Birbaumer, Niels P; Gramann, Klaus

2016-12-27

The effectiveness of today's human-machine interaction is limited by a communication bottleneck as operators are required to translate high-level concepts into a machine-mandated sequence of instructions. In contrast, we demonstrate effective, goal-oriented control of a computer system without any form of explicit communication from the human operator. Instead, the system generated the necessary input itself, based on real-time analysis of brain activity. Specific brain responses were evoked by violating the operators' expectations to varying degrees. The evoked brain activity demonstrated detectable differences reflecting congruency with or deviations from the operators' expectations. Real-time analysis of this activity was used to build a user model of those expectations, thus representing the optimal (expected) state as perceived by the operator. Based on this model, which was continuously updated, the computer automatically adapted itself to the expectations of its operator. Further analyses showed this evoked activity to originate from the medial prefrontal cortex and to exhibit a linear correspondence to the degree of expectation violation. These findings extend our understanding of human predictive coding and provide evidence that the information used to generate the user model is task-specific and reflects goal congruency. This paper demonstrates a form of interaction without any explicit input by the operator, enabling computer systems to become neuroadaptive, that is, to automatically adapt to specific aspects of their operator's mindset. Neuroadaptive technology significantly widens the communication bottleneck and has the potential to fundamentally change the way we interact with technology.

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

PubMed Central

Moorman, David E.; Aston-Jones, Gary

2015-01-01

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

Cognitive and affective theory of mind share the same local patterns of activity in posterior temporal but not medial prefrontal cortex

PubMed Central

Hofstetter, Christoph; Vuilleumier, Patrik

2014-01-01

Understanding emotions in others engages specific brain regions in temporal and medial prefrontal cortices. These activations are often attributed to more general cognitive ‘mentalizing’ functions, associated with theory of mind and also necessary to represent people’s non-emotional mental states, such as beliefs or intentions. Here, we directly investigated whether understanding emotional feelings recruit similar or specific brain systems, relative to other non-emotional mental states. We used functional magnetic resonance imaging with multivoxel pattern analysis in 46 volunteers to compare activation patterns in theory-of-mind tasks for emotions, relative to beliefs or somatic states accompanied with pain. We found a striking dissociation between the temporoparietal cortex, that exhibited a remarkable voxel-by-voxel pattern overlap between emotions and beliefs (but not pain), and the dorsomedial prefrontal cortex, that exhibited distinct (and yet nearby) patterns of activity during the judgment of beliefs and emotions in others. Pain judgment was instead associated with activity in the supramarginal gyrus, middle cingulate cortex and middle insular cortex. Our data reveal for the first time a functional dissociation within brain networks sub-serving theory of mind for different mental contents, with a common recruitment for cognitive and affective states in temporal regions, and distinct recruitment in prefrontal areas. PMID:23770622

Face Encoding and Recognition in the Human Brain

NASA Astrophysics Data System (ADS)

Haxby, James V.; Ungerleider, Leslie G.; Horwitz, Barry; Maisog, Jose Ma.; Rapoport, Stanley I.; Grady, Cheryl L.

1996-01-01

A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition. The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations.

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.

PubMed

Clarke, Hannah F; Horst, Nicole K; Roberts, Angela C

2015-03-31

Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach-avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala-anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

Neural activity to a partner's facial expression predicts self-regulation after conflict.

PubMed

Hooker, Christine I; Gyurak, Anett; Verosky, Sara C; Miyakawa, Asako; Ayduk, Ozlem

2010-03-01

Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to emotion regulation in response to laboratory-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk factor for mood and behavior problems after an interpersonal conflict. However, it remains unclear whether LPFC activity to a laboratory-based affective challenge predicts self-regulation in real life. We investigated whether LPFC activity to a laboratory-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During a functional magnetic resonance imaging scan, healthy, adult participants in committed relationships (n = 27) viewed positive, negative, and neutral facial expressions of their partners. In a three-week online daily diary, participants reported conflict occurrence, level of negative mood, rumination, and substance use. LPFC activity in response to the laboratory-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance use. Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural activity to a partner's facial expression predicts self-regulation after conflict

PubMed Central

Hooker, Christine I.; Gyurak, Anett; Verosky, Sara; Miyakawa, Asako; Ayduk, Özlem

2009-01-01

Introduction Failure to self-regulate after an interpersonal conflict can result in persistent negative mood and maladaptive behaviors. Research indicates that lateral prefrontal cortex (LPFC) activity is related to the regulation of emotional experience in response to lab-based affective challenges, such as viewing emotional pictures. This suggests that compromised LPFC function may be a risk-factor for mood and behavior problems after an interpersonal stressor. However, it remains unclear whether LPFC activity to a lab-based affective challenge predicts self-regulation in real-life. Method We investigated whether LPFC activity to a lab-based affective challenge (negative facial expressions of a partner) predicts self-regulation after a real-life affective challenge (interpersonal conflict). During an fMRI scan, healthy, adult participants in committed, dating relationships (N = 27) viewed positive, negative, and neutral facial expressions of their partners. In an online daily-diary, participants reported conflict occurrence, level of negative mood, rumination, and substance-use. Results LPFC activity in response to the lab-based affective challenge predicted self-regulation after an interpersonal conflict in daily life. When there was no interpersonal conflict, LPFC activity was not related to the change in mood or behavior the next day. However, when an interpersonal conflict did occur, ventral LPFC (VLPFC) activity predicted the change in mood and behavior the next day, such that lower VLPFC activity was related to higher levels of negative mood, rumination, and substance-use. Conclusions Low LPFC function may be a vulnerability and high LPFC function may be a protective factor for the development of mood and behavior problems after an interpersonal stressor. PMID:20004365

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

PubMed

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

2016-01-13

Neuronal activity in the lateral prefrontal cortex (LPFC) reflects the structure and cognitive demands of memory-guided sensory discrimination tasks. However, we still do not know how neuronal activity articulates in network states involved in perceiving, remembering, and comparing sensory information during such tasks. Oscillations in local field potentials (LFPs) provide fingerprints of such network dynamics. Here, we examined LFPs recorded from LPFC of macaques while they compared the directions or the speeds of two moving random-dot patterns, S1 and S2, separated by a delay. LFP activity in the theta, beta, and gamma bands tracked consecutive components of the task. In response to motion stimuli, LFP theta and gamma power increased, and beta power decreased, but showed only weak motion selectivity. In the delay, LFP beta power modulation anticipated the onset of S2 and encoded the task-relevant S1 feature, suggesting network dynamics associated with memory maintenance. After S2 onset the difference between the current stimulus S2 and the remembered S1 was strongly reflected in broadband LFP activity, with an early sensory-related component proportional to stimulus difference and a later choice-related component reflecting the behavioral decision buildup. Our results demonstrate that individual LFP bands reflect both sensory and cognitive processes engaged independently during different stages of the task. This activation pattern suggests that during elementary cognitive tasks, the prefrontal network transitions dynamically between states and that these transitions are characterized by the conjunction of LFP rhythms rather than by single LFP bands. Neurons in the brain communicate through electrical impulses and coordinate this activity in ensembles that pulsate rhythmically, very much like musical instruments in an orchestra. These rhythms change with "brain state," from sleep to waking, but also signal with different oscillation frequencies rapid changes between sensory and cognitive processing. Here, we studied rhythmic electrical activity in the monkey prefrontal cortex, an area implicated in working memory, decision making, and executive control. Monkeys had to identify and remember a visual motion pattern and compare it to a second pattern. We found orderly transitions between rhythmic activity where the same frequency channels were active in all ongoing prefrontal computations. This supports prefrontal circuit dynamics that transitions rapidly between complex rhythmic patterns during structured cognitive tasks. Copyright © 2016 the authors 0270-6474/16/360489-17$15.00/0.

Functionally dissociable influences on learning rate in a dynamic environment

PubMed Central

McGuire, Joseph T.; Nassar, Matthew R.; Gold, Joshua I.; Kable, Joseph W.

2015-01-01

Summary Maintaining accurate beliefs in a changing environment requires dynamically adapting the rate at which one learns from new experiences. Beliefs should be stable in the face of noisy data, but malleable in periods of change or uncertainty. Here we used computational modeling, psychophysics and fMRI to show that adaptive learning is not a unitary phenomenon in the brain. Rather, it can be decomposed into three computationally and neuroanatomically distinct factors that were evident in human subjects performing a spatial-prediction task: (1) surprise-driven belief updating, related to BOLD activity in visual cortex; (2) uncertainty-driven belief updating, related to anterior prefrontal and parietal activity; and (3) reward-driven belief updating, a context-inappropriate behavioral tendency related to activity in ventral striatum. These distinct factors converged in a core system governing adaptive learning. This system, which included dorsomedial frontal cortex, responded to all three factors and predicted belief updating both across trials and across individuals. PMID:25459409

When giving is good: Ventromedial prefrontal cortex activation for others’ intentions

PubMed Central

Cooper, Jeffrey C.; Kreps, Tamar A.; Wiebe, Taylor; Pirkl, Tristana; Knutson, Brian

2010-01-01

Summary In social decision-making, people care both about others’ outcomes and their intentions to help or harm. How the brain integrates representations of others’ intentions with their outcomes, however, is unknown. In this study, participants inferred others’ decisions in an economic game during functional magnetic resonance imaging. When the game was described in terms of donations, ventromedial prefrontal cortex (VMPFC) activation increased for inferring generous play and decreased for inferring selfish play. When the game was described in terms of individual savings, however, VMPFC activation did not distinguish between strategies. Distinct medial prefrontal regions also encoded consistency with situational norms. A separate network, including right temporoparietal junction and parahippocampal gyrus, was more activated for inferential errors in the donation than in the savings condition. These results for the first time demonstrate that neural responses to others’ generosity or selfishness depend not only on their actions but also on their perceived intentions. PMID:20696386

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

PubMed

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

2017-11-02

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

Emotional eating and routine restraint scores are associated with activity in brain regions involved in urge and self-control.

PubMed

Wood, Samantha M W; Schembre, Susan M; He, Qinghua; Engelmann, Jeffrey M; Ames, Susan L; Bechara, Antoine

2016-10-15

Researchers have proposed a variety of behavioral traits that may lead to weight gain and obesity; however, little is known about the neurocognitive mechanisms underlying these weight-related eating behaviors. In this study, we measured activation of reward circuitry during a task requiring response and inhibition to food stimuli. We assessed participants' emotional eating, external eating, and two subscales of dietary restraint-routine restraint and compensatory restraint-using the Weight-Related Eating Questionnaire. For routine restraint, we found positive associations with activation in the insula, dorsolateral prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex and ventromedial prefrontal cortex in response to high-calorie versus low-calorie foods. For emotional eating, we found positive associations with insula and dorsolateral prefrontal cortex activation in response to high-calorie versus low-calorie foods. We also found positive associations between emotional eating and dorsolateral prefrontal cortex activation in response to approach versus inhibition towards high-calorie foods. Thus, our results demonstrate an increase in activation across brain regions related to self-control and urges in response to high-calorie food associated with both emotional eating and routine restraint. Overall, these results support the construct validity of both emotional eating and routine restraint and provide preliminary evidence that these subscales have similar neural correlates. Copyright © 2016 Elsevier Inc. All rights reserved.

Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence.

PubMed

Driesen, Naomi R; Leung, Hoi-Chung; Calhoun, Vincent D; Constable, R Todd; Gueorguieva, Ralitza; Hoffman, Ralph; Skudlarski, Pawel; Goldman-Rakic, Patricia S; Krystal, John H

2008-12-15

Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases. Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load. Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task. Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.

Common and distinct networks for self-referential and social stimulus processing in the human brain.

PubMed

Herold, Dorrit; Spengler, Stephanie; Sajonz, Bastian; Usnich, Tatiana; Bermpohl, Felix

2016-09-01

Self-referential processing is a complex cognitive function, involving a set of implicit and explicit processes, complicating investigation of its distinct neural signature. The present study explores the functional overlap and dissociability of self-referential and social stimulus processing. We combined an established paradigm for explicit self-referential processing with an implicit social stimulus processing paradigm in one fMRI experiment to determine the neural effects of self-relatedness and social processing within one study. Overlapping activations were found in the orbitofrontal cortex and in the intermediate part of the precuneus. Stimuli judged as self-referential specifically activated the posterior cingulate cortex, the ventral medial prefrontal cortex, extending into anterior cingulate cortex and orbitofrontal cortex, the dorsal medial prefrontal cortex, the ventral and dorsal lateral prefrontal cortex, the left inferior temporal gyrus, and occipital cortex. Social processing specifically involved the posterior precuneus and bilateral temporo-parietal junction. Taken together, our data show, not only, first, common networks for both processes in the medial prefrontal and the medial parietal cortex, but also, second, functional differentiations for self-referential processing versus social processing: an anterior-posterior gradient for social processing and self-referential processing within the medial parietal cortex and specific activations for self-referential processing in the medial and lateral prefrontal cortex and for social processing in the temporo-parietal junction.

Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment

PubMed Central

Apergis-Schoute, Annemieke M; Vaghi, Matilde M; Banca, Paula; Gillan, Claire M; Voon, Valerie; Chamberlain, Samuel R; Cinosi, Eduardo; Reid, Jemma; Shahper, Sonia; Bullmore, Edward T; Sahakian, Barbara J; Robbins, Trevor W

2018-01-01

Abstract Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder. PMID:29036632

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

Neurofunctional Differences Among Youth With and at Varying Risk for Developing Mania.

PubMed

Welge, Jeffrey A; Saliba, Lawrence J; Strawn, Jeffrey R; Eliassen, James C; Patino, L Rodrigo; Adler, Caleb M; Weber, Wade; Schneider, Marguerite Reid; Barzman, Drew H; Strakowski, Stephen M; DelBello, Melissa P; McNamara, Robert K

2016-11-01

To examine prefrontal and amygdala activation during emotional processing in youth with or at varying risk for developing mania to identify candidate central prodromal risk biomarkers. Four groups of medication-free adolescents (10-20 years old) participated: adolescents with first-episode bipolar I disorder (BP-I; n = 32), adolescents with a parent with bipolar disorder and a depressive disorder (at-risk depressed [ARD]; n = 32), healthy adolescents with a parent with bipolar disorder (at-risk healthy [ARH]; n = 32), and healthy adolescents with no personal or family history of psychiatric illness (healthy comparison [HC]; n = 32). Participants underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. Region-of-interest analyses were performed for the bilateral amygdala and for subregions of the ventrolateral prefrontal cortex and anterior cingulate cortex. Overall, no group differences in bilateral amygdala and ventrolateral prefrontal cortex (Brodmann area [BA] 45/47) activation during emotional or neutral stimuli were observed. The BP-I group exhibited lower right pregenual anterior cingulate cortex activation compared with the HC group, and activation in the left BA 44 was greater in the ARH and ARD groups compared with the HC group. BP-I and ARD groups exhibited blunted activation in the right BA 10 compared with the ARH group. During emotional processing, amygdala and ventrolateral prefrontal cortex (BA 45/47) activation does not differ in youth with or at increasing risk for BP-I. However, blunted pregenual anterior cingulate cortex activation in first-episode mania could represent an illness biomarker, and greater prefrontal BA 10 and BA 44 activations in at-risk youth could represent a biomarker of risk or resilience warranting additional investigation in prospective longitudinal studies. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

PubMed Central

Carhart-Harris, Robin L.; Erritzoe, David; Williams, Tim; Stone, James M.; Reed, Laurence J.; Colasanti, Alessandro; Tyacke, Robin J.; Leech, Robert; Malizia, Andrea L.; Murphy, Kevin; Hobden, Peter; Evans, John; Feilding, Amanda; Wise, Richard G.; Nutt, David J.

2012-01-01

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition. PMID:22308440

The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia.

PubMed

Durstewitz, Daniel; Seamans, Jeremy K

2008-11-01

There is now general consensus that at least some of the cognitive deficits in schizophrenia are related to dysfunctions in the prefrontal cortex (PFC) dopamine (DA) system. At the cellular and synaptic level, the effects of DA in PFC via D1- and D2-class receptors are highly complex, often apparently opposing, and hence difficult to understand with regard to their functional implications. Biophysically realistic computational models have provided valuable insights into how the effects of DA on PFC neurons and synaptic currents as measured in vitro link up to the neural network and cognitive levels. They suggest the existence of two discrete dynamical regimes, a D1-dominated state characterized by a high energy barrier among different network patterns that favors robust online maintenance of information and a D2-dominated state characterized by a low energy barrier that is beneficial for flexible and fast switching among representational states. These predictions are consistent with a variety of electrophysiological, neuroimaging, and behavioral results in humans and nonhuman species. Moreover, these biophysically based models predict that imbalanced D1:D2 receptor activation causing extremely low or extremely high energy barriers among activity states could lead to the emergence of cognitive, positive, and negative symptoms observed in schizophrenia. Thus, combined experimental and computational approaches hold the promise of allowing a detailed mechanistic understanding of how DA alters information processing in normal and pathological conditions, thereby potentially providing new routes for the development of pharmacological treatments for schizophrenia.

[Effects of prefrontal ablations on the reaction of the active choice of feeder under different probability and value of the reinforcement on dog].

PubMed

Preobrazhenskaia, L A; Ioffe, M E; Mats, V N

2004-01-01

The role of the prefrontal cortex was investigated on the reaction of the active choice of the two feeders under changes value and probability reinforcement. The experiments were performed on 2 dogs with prefrontal ablation (g. proreus). Before the lesions the dogs were taught to receive food in two different feeders to conditioned stimuli with equally probable alimentary reinforcement. After ablation in the inter-trial intervals the dogs were running from the one feeder to another. In the answer to conditioned stimuli for many times the dogs choose the same feeder. The disturbance of the behavior after some times completely restored. In the experiments with competition of probability events and values of reinforcement the dogs chose the feeder with low-probability but better quality of reinforcement. In the experiments with equal value but different probability the intact dogs chose the feeder with higher probability. In our experiments the dogs with prefrontal lesions chose the each feeder equiprobably. Thus in condition of free behavior one of different functions of the prefrontal cortex is the reactions choose with more probability of reinforcement.

The direct pathway from the brainstem reticular formation to the cerebral cortex in the ascending reticular activating system: A diffusion tensor imaging study.

PubMed

Jang, Sung Ho; Kwon, Hyeok Gyu

2015-10-08

Precise evaluation of the ascending reticular activating system (ARAS) is important for diagnosis, prediction of prognosis, and management of patients with disorders of impaired consciousness. In the current study, we attempted to reconstruct the direct neural pathway between the brainstem reticular formation (RF) and the cerebral cortex in normal subjects, using diffusion tensor imaging (DTI). Forty-one healthy subjects were recruited for this study. DTIs were performed using a sensitivity-encoding head coil at 1.5Tesla with FMRIB Software Library. For connectivity of the brainstem RF, we used two regions of interest (ROIs) for the brainstem RF (seed ROI) and the thalamus and hypothalamus (exclusion ROI). Connectivity was defined as the incidence of connection between the brainstem RF and target brain regions at the threshold of 5 and 50 streamlines. Regarding the thresholds of 5 and 50, the brainstem RF showed high connectivity to the lateral prefrontal cortex (lPFC, 67.1% and 20.7%) and ventromedial prefrontal cortex (vmPFC, 50.0% and 18.3%), respectively. In contrast, the brainstem RF showed low connectivity to the primary motor cortex (31.7% and 3.7%), premotor cortex (24.4% and 3.7%), primary somatosensory cortex (23.2% and 2.4%), orbitofrontal cortex (17.1% and 7.3%), and posterior parietal cortex (12.2% and 0%), respectively. The brainstem RF was mainly connected to the prefrontal cortex, particularly lPFC and vmPFC. We believe that the methodology and results of this study would be useful to clinicians involved in the care of patients with impaired consciousness and researchers in studies of the ARAS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2007-10-17

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

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

PubMed Central

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

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic cocaine self-administration in rats leads to decrements in medial prefrontal structural and functional plasticity. Notably, these impairments were largely accounted for in rats that self-administered cocaine compared with yoked counterparts. Moreover, we verified previous reports showing that adrenocortical output is augmented by cocaine administration and is more protracted in rats that were permitted to receive the drug contingently instead of passively. These studies suggest that increased adrenocortical activity resulting from cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. PMID:26311772

Effects of aripiprazole versus risperidone on brain activation during planning and social-emotional evaluation in schizophrenia: A single-blind randomized exploratory study.

PubMed

Liemburg, Edith J; van Es, Frank; Knegtering, Henderikus; Aleman, André

2017-10-03

Impaired function of prefrontal brain networks may be the source of both negative symptoms and neurocognitive problems in psychotic disorders. Whereas most antipsychotics may decrease prefrontal activation, the partial dopamine D2-receptor agonist aripiprazole is hypothesized to improve prefrontal function. This study investigated whether patients with a psychotic disorder would show stronger activation of prefrontal areas and associated regions after treatment with aripiprazole compared to risperidone treatment. In this exploratory pharmacological neuroimaging study, 24 patients were randomly assigned to either aripiprazole or risperidone. At baseline and after nine weeks treatment they underwent an interview and MRI session. Here we report on brain activation (measured with arterial spin labeling) during performance of two tasks, the Tower of London and the Wall of Faces. Aripiprazole treatment decreased activation of the middle frontal, superior frontal and occipital gyrus (ToL) and medial temporal and inferior frontal gyrus, putamen and cuneus (WoF), while activation increased after risperidone. Activation increased in the ventral anterior cingulate and posterior insula (ToL), and superior frontal, superior temporal and precentral gyrus (WoF) after aripiprazole treatment and decreased after risperidone. Both treatment groups had increased ventral insula activation (ToL) and middle temporal gyrus (WoF), and decreased occipital cortex, precuneus and caudate head activation (ToL) activation. In conclusion, patients treated with aripiprazole may need less frontal resources for planning performance and may show increased frontotemporal and frontostriatal reactivity to emotional stimuli. More research is needed to corroborate and extend these preliminary findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms

PubMed Central

Wall, Anders; Olsson, Ulf; Marteinsdottir, Ina; Holstad, Maria; Ågren, Hans; Långström, Bengt; Naessén, Tord

2016-01-01

Study Objective To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. Background Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. Methods Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity–a proxy for serotonin precursor uptake and synthesis–was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single “whole brain”. Results There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual—follicular) correlated with changes in self ratings of ‘irritability’ for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual—follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation. Conclusion Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies. PMID:27617751

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

PubMed

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

2018-03-01

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

Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age

PubMed Central

Axelsson, Jan; Riklund, Katrine; Nyberg, Lars; Dayan, Peter; Bäckman, Lars

2017-01-01

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. PMID:28870286

Enhanced Neural Responses to Imagined Primary Rewards Predict Reduced Monetary Temporal Discounting.

PubMed

Hakimi, Shabnam; Hare, Todd A

2015-09-23

The pervasive tendency to discount the value of future rewards varies considerably across individuals and has important implications for health and well-being. Here, we used fMRI with human participants to examine whether an individual's neural representation of an imagined primary reward predicts the degree to which the value of delayed monetary payments is discounted. Because future rewards can never be experienced at the time of choice, imagining or simulating the benefits of a future reward may play a critical role in decisions between alternatives with either immediate or delayed benefits. We found that enhanced ventromedial prefrontal cortex response during imagined primary reward receipt was correlated with reduced discounting in a separate monetary intertemporal choice task. Furthermore, activity in enhanced ventromedial prefrontal cortex during reward imagination predicted temporal discounting behavior both between- and within-individual decision makers with 62% and 73% mean balanced accuracy, respectively. These results suggest that the quality of reward imagination may impact the degree to which future outcomes are discounted. Significance statement: We report a novel test of the hypothesis that an important factor influencing the discount rate for future rewards is the quality with which they are imagined or estimated in the present. Previous work has shown that temporal discounting is linked to individual characteristics ranging from general intelligence to the propensity for addiction. We demonstrate that individual differences in a neurobiological measure of primary reward imagination are significantly correlated with discounting rates for future monetary payments. Moreover, our neurobiological measure of imagination can be used to accurately predict choice behavior both between and within individuals. These results suggest that improving reward imagination may be a useful therapeutic target for individuals whose high discount rates promote detrimental behaviors. Copyright © 2015 the authors 0270-6474/15/3513103-07$15.00/0.

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

PubMed

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

2016-03-30

The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinase involved in neuronal differentiation and synaptic plasticity and a major candidate of Down syndrome brain alterations and cognitive deficits. DYRK1A is strongly expressed in the cerebral cortex, and its overexpression leads to defective cortical pyramidal cell morphology, synaptic plasticity deficits, and altered excitation/inhibition balance. These previous observations, however, do not allow predicting how the behavior of the prefrontal cortex (PFC) network and the resulting properties of its emergent activity are affected. Here, we integrate functional, anatomical, and computational data describing the prefrontal network alterations in transgenic mice overexpressingDyrk1A(TgDyrk1A). Usingin vivoextracellular recordings, we show decreased firing rate and gamma frequency power in the prefrontal network of anesthetized and awakeTgDyrk1Amice. Immunohistochemical analysis identified a selective reduction of vesicular GABA transporter punctae on parvalbumin positive neurons, without changes in the number of cortical GABAergic neurons in the PFC ofTgDyrk1Amice, which suggests that selective disinhibition of parvalbumin interneurons would result in an overinhibited functional network. Using a conductance-based computational model, we quantitatively demonstrate that this alteration could explain the observed functional deficits including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. DYRK1Ais a major candidate gene in Down syndrome. Its overexpression results into altered cognitive abilities, explained by defective cortical microarchitecture and excitation/inhibition imbalance. An open question is how these deficits impact the functionality of the prefrontal cortex network. Combining functional, anatomical, and computational approaches, we identified decreased neuronal firing rate and deficits in gamma frequency in the prefrontal cortices of transgenic mice overexpressingDyrk1A We also identified a reduction of vesicular GABA transporter punctae specifically on parvalbumin positive interneurons. Using a conductance-based computational model, we demonstrate that this decreased inhibition on interneurons recapitulates the observed functional deficits, including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. Copyright © 2016 the authors 0270-6474/16/363649-12$15.00/0.

[Psychotherapy of Depression as Neurobiological Process - Evidence from Neuroimaging].

PubMed

Rubart, Antonie; Hohagen, Fritz; Zurowski, Bartosz

2018-06-01

Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training. © Georg Thieme Verlag KG Stuttgart · New York.

[Effects of Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats].

PubMed

Tong, Hai-Ying; Wu, Jisiguleng; Bai, Liang-Feng; Bao, Wu-Ye; Hu, Rilebagen; Li, Jing; Zhang, Yue

2014-05-01

To observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats. Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA). The AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill. The AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Ventral Midline Thalamus Is Critical for Hippocampal–Prefrontal Synchrony and Spatial Working Memory

PubMed Central

Hallock, Henry L.; Wang, Arick

2016-01-01

Maintaining behaviorally relevant information in spatial working memory (SWM) requires functional synchrony between the dorsal hippocampus and medial prefrontal cortex (mPFC). However, the mechanism that regulates synchrony between these structures remains unknown. Here, we used a unique dual-task approach to compare hippocampal–prefrontal synchrony while rats switched between an SWM-dependent task and an SWM-independent task within a single behavioral session. We show that task-specific representations in mPFC neuronal populations are accompanied by SWM-specific oscillatory synchrony and directionality between the dorsal hippocampus and mPFC. We then demonstrate that transient inactivation of the reuniens and rhomboid (Re/Rh) nuclei of the ventral midline thalamus abolished only the SWM-specific activity patterns that were seen during dual-task sessions within the hippocampal–prefrontal circuit. These findings demonstrate that Re/Rh facilitate bidirectional communication between the dorsal hippocampus and mPFC during SWM, providing evidence for a causal role of Re/Rh in regulating hippocampal–prefrontal synchrony and SWM-directed behavior. SIGNIFICANCE STATEMENT Hippocampal–prefrontal synchrony has long been thought to be critical for spatial working memory (SWM) and the ventral midline thalamic reuniens and rhomboid nuclei (Re/Rh) have long been considered a potential site for synchronizing the hippocampus and medial prefrontal cortex. However, the hypothesis that Re/Rh are critical for hippocampal–prefrontal synchrony and SWM has not been tested. We first used a dual-task approach to identify SWM-specific patterns of hippocampal–prefrontal synchrony. We then demonstrated that Re/Rh inactivation concurrently disrupted SWM-specific behavior and the SWM-specific patterns of hippocampal–prefrontal synchrony seen during dual-task performance. These results provide the first direct evidence that Re/Rh contribute to SWM by modulating hippocampal–prefrontal synchrony. PMID:27511010

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

PubMed

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

2012-11-01

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

Working memory performance and neural activity in prefrontal cortex of peripubertal monkeys

PubMed Central

Zhou, Xin; Zhu, Dantong; Qi, Xue-Lian; Lees, Cynthia J.; Bennett, Allyson J.; Salinas, Emilio; Stanford, Terrence R.

2013-01-01

The dorsolateral prefrontal cortex matures late into adolescence or early adulthood. This pattern of maturation mirrors working memory abilities, which continue to improve into adulthood. However, the nature of the changes that prefrontal neuronal activity undergoes during this process is poorly understood. We investigated behavioral performance and neural activity in working memory tasks around the time of puberty, a developmental event associated with the release of sex hormones and significant neurological change. The developmental stages of male rhesus monkeys were evaluated with a series of morphometric, hormonal, and radiographic measures. Peripubertal monkeys were trained to perform an oculomotor delayed response task and a variation of this task involving a distractor stimulus. We found that the peripubertal monkeys tended to abort a relatively large fraction of trials, and these were associated with low levels of task-related neuronal activity. However, for completed trials, accuracy in the delayed saccade task was high and the appearance of a distractor stimulus did not impact performance significantly. In correct trials delay period activity was robust and was not eliminated by the presentation of a distracting stimulus, whereas in trials that resulted in errors the sustained cue-related activity was significantly weaker. Our results show that in peripubertal monkeys the prefrontal cortex is capable of generating robust persistent activity in the delay periods of working memory tasks, although in general it may be more prone to stochastic failure than in adults. PMID:24047904

Alcohol Attenuates Load-related Activation During a Working Memory Task: Relation to Level of Response to Alcohol

PubMed Central

Paulus, Martin P.; Tapert, Susan F.; Pulido, Carmen; Schuckit, Marc A.

2008-01-01

Background A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Method Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level–dependent activation to an event-related visual working memory test was examined. Results The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load–dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Conclusion Low-level responders relative to high-level responders exhibited an increased working memory load–dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol. PMID:16899039

Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth.

PubMed

Bertocci, Michele A; Bebko, Genna; Dwojak, Amanda; Iyengar, Satish; Ladouceur, Cecile D; Fournier, Jay C; Versace, Amelia; Perlman, Susan B; Almeida, Jorge R C; Travis, Michael J; Gill, Mary Kay; Bonar, Lisa; Schirda, Claudiu; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Frazier, Thomas; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2017-05-01

Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort. Forty-one youth completed two study visits (mean=21.3 months). Elastic-net regression (Multiple response Gaussian family) identified emotional regulation neural circuitry that changed in association with changes in depression, mania, anxiety, affect lability, and positive mood and energy dysregulation, accounting for clinical and demographic variables. Non-zero coefficients between change in the above symptom measures and change in activity over the inter-scan interval were identified in right amygdala and left ventrolateral prefrontal cortex. Differing patterns of neural activity change were associated with changes in each of the above symptoms over time. Specifically, from Scan1 to Scan2, worsening affective lability and depression severity were associated with increased right amygdala and left ventrolateral prefrontal cortical activity. Worsening anxiety and positive mood and energy dysregulation were associated with decreased right amygdala and increased left ventrolateral prefrontal cortical activity. Worsening mania was associated with increased right amygdala and decreased left ventrolateral prefrontal cortical activity. These changes in neural activity between scans accounted for 13.6% of the variance; that is 25% of the total explained variance (39.6%) in these measures. Distinct neural mechanisms underlie changes in different mood and anxiety symptoms overtime.

Monitoring of prefrontal cortex activation during verbal n-back task with 24-channel functional NIRS imager

NASA Astrophysics Data System (ADS)

Li, Chengjun; Gong, Hui; Gan, Zhuo; Luo, Qingming

2005-01-01

Human prefrontal cortex (PFC) helps mediate working memory (WM), a system that is used for temporary storage and manipulation of information and is involved with many higher-level cognitive functions. Here, we report a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by verbal WM task. For investigating the effect of memory load on brain activation, we adopted the "n-back" task in which subjects must decide for each present letter whether it matches the letter presented n items back in sequence. 27 subjects (ages 18-24, 13 females) participated in the work. Concentration changes in oxy-Hb (HbO2), deoxy-Hb (Hb), and total-Hb (HbT) in the subjects" prefrontal cortex were monitored by a 24-channel functional NIRS imager. The cortical activations and deactivations were found in left ventrolateral PFC and bilateral dorsolateral PFC. As memory load increased, subjects showed poorer behavioral performance as well as monotonically increasing magnitudes of the activations and deactivations in PFC.

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

NASA Astrophysics Data System (ADS)

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

2011-03-01

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

EEG activity during the spatial span task in young men: Differences between short-term and working memory.

PubMed

Guevara, Miguel Angel; Cruz Paniagua, Edwin Iván; Hernández González, Marisela; Sandoval Carrillo, Ivett Karina; Almanza Sepúlveda, Mayra Linné; Hevia Orozco, Jorge Carlos; Amezcua Gutiérrez, Claudia

2018-03-15

Short-term memory and working memory are two closely-related concepts that involve the prefrontal and parietal areas. These two types of memory have been evaluated by means of the spatial span task in its forward and backward conditions, respectively. To determine possible neurofunctional differences between them, this study recorded electroencephalographic activity (EEG) in the frontopolar (Fp1, Fp2), dorsolateral (F3, F4), and parietal (P3 and P4) areas during performance of the forward and backward conditions of this task in young men. The backward condition (an indicator of working memory) was characterized by fewer correct answers, higher absolute power (AP) of the delta band in dorsolateral areas, and a lower correlation between frontopolar and dorsolateral regions in the fast bands (alpha, beta and gamma), mainly in the right hemisphere. The prefrontal EEG changes during backward performance may be associated with the higher attentional demands and inhibition processes required to invert the order of reproduction of a sequence. These data provide evidence that the forward and backward conditions of the spatial span task can be distinguished on the basis of neurofunctional activity and performance, and that each one is associated with a distinct pattern of electrical activity and synchronization between prefrontal areas. The higher AP of the delta band and lower correlation of the fast bands, particularly between right prefrontal areas during the backward condition of this visuospatial task, suggest greater participation by the right prefrontal areas in working memory. Copyright © 2018 Elsevier B.V. All rights reserved.

Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

PubMed

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

Variability in Prefrontal Hemodynamic Response during Exposure to Repeated Self-Selected Music Excerpts, a Near-Infrared Spectroscopy Study

PubMed Central

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes. PMID:25837268

Decreased prefrontal cortical sensitivity to monetary reward is associated with impaired motivation and self-control in cocaine addiction

PubMed Central

Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Zhang, Lei; Cottone, Lisa A.; Maloney, Thomas; Telang, Frank; Caparelli, Elisabeth C.; Chang, Linda; Ernst, Thomas; Samaras, Dimitris; Squires, Nancy K.; Volkow, Nora D.

2008-01-01

Objective To examine the brain’s sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with activations in the orbitofrontal cortex. For cocaine subjects, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions These findings suggest that in cocaine addiction (1) activation of the corticolimbic reward circuit to gradations of money is altered; (2) lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and (3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication. PMID:17202543

A model for integrating elementary neural functions into delayed-response behavior.

PubMed

Gisiger, Thomas; Kerszberg, Michel

2006-04-01

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asensio, S.; Goldstein, R.; Asensio, S.

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

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

PubMed Central

Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.; Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Volkow, Nora D.; Goldstein, Rita Z.

2009-01-01

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to non-drug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [11C]raclopride and positron emission tomography and response to monetary reward was measured (an average of 3 years later) with functional magnetic resonance imaging in seven cocaine addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a non-drug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine addicted individuals. PMID:20034014

Novelty response of rats determines the effect of prefrontal alpha-2 adrenoceptor modulation on anxiety.

PubMed

Uzsoki, B; Tóth, M; Hernádi, I

2011-07-25

In this study we provide evidence that animals of the same population, although identical in age and sex, have individual reactions to the prefrontal modulation of adrenoceptors. We have examined the dose-dependent action of α(2)-adrenoceptor agents on the anxiety of rats with different response to novelty in the elevated plus maze (EPM) apparatus. Rats were divided into high (HR) and low responder (LR) groups based on their locomotor activity in a novel open field environment. HR rats also showed increased locomotion and low anxiety in the EPM. Prefrontal injection of α(2)-receptor antagonist yohimbine, BRL44408 or imiloxan caused anxiety only in HR rats. The α(2A/D)-receptor agonist guanfacine increased anxiety levels of both groups. However, the effective dose was lower in HR rats. The present results propose different prefrontal adrenoceptor sensitivity of rats showing distinct baseline activity levels. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Decreased leftward bias of prefrontal activity in autism spectrum disorder revealed by functional near-infrared spectroscopy.

PubMed

Tamura, Ryu; Kitamura, Hideaki; Endo, Taro; Abe, Ryo; Someya, Toshiyuki

2012-01-01

Hemodynamic responses in rostral prefrontal cortex (RoPFC) were measured by functional near-infrared spectroscopy. Although performance level was equal, autistic patients showed a decrease in leftward bias of the balance between right and left RoPFC activity when compared with typically developing children when anatomical imitation was contrasted with mirror-image imitation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Acting, seeing, and conscious awareness.

PubMed

Passingham, R E; Lau, H C

2017-06-13

We argue that there is a relation between the judgements that 'I did it' and 'I saw it'. Both are statements are about the individual, not just the world. We show that the dorsal prefrontal cortex is activated both when human subjects judge that they are the agents of their actions and when they judge that they are confident that they have seen a masked visual stimulus. Macaque monkeys have also been taught to report whether they have or have not seen visual stimuli and cells can be found in the dorsal prefrontal cortex that distinguish between 'seen' and 'not seen'. The judgement is abstract in that it applies largely irrespective of the nature and location of the stimulus. We suggest that the reason why the prefrontal cortex is involved is that it evolved in primates, adapted by searching for fruit and leaves and using their hands to retrieve them. There is cell activity in the dorsal prefrontal cortex that relates to eye movements, covert attention and visual search; activity that relates to learning abstract rules; and activity that relates to the planning of the hand movements that are appropriate. We propose that this is the reason why this area is involved in making judgements about both agency and visual detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Noninvasive imaging of prefrontal activation during attention-demanding tasks performed while walking using a wearable optical topography system

NASA Astrophysics Data System (ADS)

Atsumori, Hirokazu; Kiguchi, Masashi; Katura, Takusige; Funane, Tsukasa; Obata, Akiko; Sato, Hiroki; Manaka, Takaaki; Iwamoto, Mitsumasa; Maki, Atsushi; Koizumi, Hideaki; Kubota, Kisou

2010-07-01

Optical topography (OT) based on near-infrared spectroscopy is a noninvasive technique for mapping the relative concentration changes in oxygenated and deoxygenated hemoglobin (oxy- and deoxy-Hb, respectively) in the human cerebral cortex. In our previous study, we developed a small and light wearable optical topography (WOT) system that covers the entire forehead for monitoring prefrontal activation. In the present study, we examine whether the WOT system is applicable to OT measurement while walking, which has been difficult with conventional OT systems. We conduct OT measurements while subjects perform an attention-demanding (AD) task of balancing a ping-pong ball on a small card while walking. The measured time course and power spectra of the relative concentration changes in oxy- and deoxy-Hb show that the step-related changes in the oxy- and deoxy-Hb signals are negligible compared to the task-related changes. Statistical assessment of the task-related changes in the oxy-Hb signals show that the dorsolateral prefrontal cortex and rostral prefrontal area are significantly activated during the AD task. These results suggest that our functional imaging technique with the WOT system is applicable to OT measurement while walking, and will be a powerful tool for evaluating brain activation in a natural environment.

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

PubMed Central

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

2009-01-01

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

The relation of general socio-emotional processing to parenting specific behavior: a study of mothers with and without posttraumatic stress disorder

PubMed Central

Moser, Dominik A.; Aue, Tatjana; Suardi, Francesca; Manini, Aurélia; Sancho Rossignol, Ana; Cordero, Maria I.; Merminod, Gaëlle; Ansermet, François; Rusconi Serpa, Sandra; Favez, Nicolas; Schechter, Daniel S.

2015-01-01

Socio-emotional information processing during everyday human interactions has been assumed to translate to social-emotional information processing when parenting a child. Yet, few studies have examined whether this is indeed the case. This study aimed to improve on this by connecting the functional neuroimaging data when seeing socio-emotional interactions that are not parenting specific to observed maternal sensitivity. The current study considered 45 mothers of small children (12–42 months of age). It included healthy controls (HC) and mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), as well as mothers without PTSD, both with and without IPV exposure. We found that anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC) activity correlated negatively with observed maternal sensitivity when mothers watched videos of menacing vs. prosocial adult male–female interactions. This relationship was independent of whether mothers were HC or had IPV-PTSD. We also found dorsolateral prefrontal cortex (dlPFC) activity to be correlated negatively with maternal sensitivity when mothers watched any kind of arousing adult interactions. With regards to ACC and vmPFC activity, we interpret our results to mean that the ease of general emotional information integration translates to parenting-specific behavior. Our dlPFC activity findings support the idea that the efficiency of top-down control of socio-emotional processing in non-parenting specific contexts may be predictive of parenting behavior. PMID:26578996

Prefrontal spatial working memory network predicts animal's decision making in a free choice saccade task

PubMed Central

Mochizuki, Kei

2015-01-01

While neurons in the lateral prefrontal cortex (PFC) encode spatial information during the performance of working memory tasks, they are also known to participate in subjective behavior such as spatial attention and action selection. In the present study, we analyzed the activity of primate PFC neurons during the performance of a free choice memory-guided saccade task in which the monkeys needed to choose a saccade direction by themselves. In trials when the receptive field location was subsequently chosen by the animal, PFC neurons with spatially selective visual response started to show greater activation before cue onset. This result suggests that the fluctuation of firing before cue presentation prematurely biased the representation of a certain spatial location and eventually encouraged the subsequent choice of that location. In addition, modulation of the activity by the animal's choice was observed only in neurons with high sustainability of activation and was also dependent on the spatial configuration of the visual cues. These findings were consistent with known characteristics of PFC neurons in information maintenance in spatial working memory function. These results suggest that precue fluctuation of spatial representation was shared and enhanced through the working memory network in the PFC and could finally influence the animal's free choice of saccade direction. The present study revealed that the PFC plays an important role in decision making in a free choice condition and that the dynamics of decision making are constrained by the network architecture embedded in this cortical area. PMID:26490287

Stimulus onset predictability modulates proactive action control in a Go/No-go task

PubMed Central

Berchicci, Marika; Lucci, Giuliana; Spinelli, Donatella; Di Russo, Francesco

2015-01-01

The aim of the study was to evaluate whether the presence/absence of visual cues specifying the onset of an upcoming, action-related stimulus modulates pre-stimulus brain activity, associated with the proactive control of goal-directed actions. To this aim we asked 12 subjects to perform an equal probability Go/No-go task with four stimulus configurations in two conditions: (1) uncued, i.e., without any external information about the timing of stimulus onset; and (2) cued, i.e., with external visual cues providing precise information about the timing of stimulus onset. During task both behavioral performance and event-related potentials (ERPs) were recorded. Behavioral results showed faster response times in the cued than uncued condition, confirming existing literature. ERPs showed novel results in the proactive control stage, that started about 1 s before the motor response. We observed a slow rising prefrontal positive activity, more pronounced in the cued than the uncued condition. Further, also pre-stimulus activity of premotor areas was larger in cued than uncued condition. In the post-stimulus period, the P3 amplitude was enhanced when the time of stimulus onset was externally driven, confirming that external cueing enhances processing of stimulus evaluation and response monitoring. Our results suggest that different pre-stimulus processing come into play in the two conditions. We hypothesize that the large prefrontal and premotor activities recorded with external visual cues index the monitoring of the external stimuli in order to finely regulate the action. PMID:25964751

Increases in brain activity during social competition predict decreases in working memory performance and later recall.

PubMed

DiMenichi, Brynne C; Tricomi, Elizabeth

2017-01-01

In our fMRI experiment, participants completed a learning task in both a noncompetitive and a socially competitive learning environment. Despite reporting a preference for completing the task while competing, participants remembered significantly more during the task and later recalled more from the noncompetitive learning environment. Furthermore, during working memory maintenance, there was performance-related deactivation in the medial prefrontal cortex (mPFC) and the precuneus/PCC. During feedback presentation, there was greater activation in the mPFC and the precuneus/PCC while competing. Differential activation in the precuneus/PCC predicted worse later recall for information learned competitively. Since previous research suggests that the mPFC is involved in social-referencing, while the precuneus/PCC is implicated in off-task thoughts, our results suggest that receiving feedback regarding competition produces more activation in brain regions implicated in social interaction, as well as task distraction. While competition may make a task more enjoyable, the goal of winning may distract from maximizing performance. Hum Brain Mapp 38:457-471, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Does Feedback-Related Brain Response during Reinforcement Learning Predict Socio-motivational (In-)dependence in Adolescence?

PubMed Central

Raufelder, Diana; Boehme, Rebecca; Romund, Lydia; Golde, Sabrina; Lorenz, Robert C.; Gleich, Tobias; Beck, Anne

2016-01-01

This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students (N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students’ membership to the independent MT, or the peer-and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students’ individual motivation and (2) its potential neurobiological basis. PMID:27199873

The Neural Correlates of Self-Regulatory Fatigability During Inhibitory Control of Eye Blinking.

PubMed

Abi-Jaoude, Elia; Segura, Barbara; Cho, Sang Soo; Crawley, Adrian; Sandor, Paul

2018-05-30

The capacity to regulate urges is an important human characteristic associated with a range of social and health outcomes. Self-regulatory capacity has been postulated to have a limited reserve, which when depleted leads to failure. The authors aimed to investigate the neural correlates of self-regulatory fatigability. Functional MRI was used to detect brain activations in 19 right-handed healthy subjects during inhibition of eye blinking, in a block design. The increase in number of blinks during blink inhibition from the first to the last block was used as covariate of interest. There was an increase in the number of eye blinks escaping inhibitory control across blink inhibition blocks, whereas there was no change in the number of eye blinks occurring during rest blocks. Inhibition of blinking activated a wide network bilaterally, including the inferior frontal gyrus, dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, supplementary motor area, and caudate. Deteriorating performance was associated with activity in orbitofrontal cortex, ventromedial prefrontal cortex, rostroventral anterior cingulate cortex, precuneus, somatosensory, and parietal areas. As anticipated, effortful eye-blink control resulted in activation of prefrontal control areas and regions involved in urge and interoceptive processing. Worsening performance was associated with activations in brain areas involved in urge, as well as regions involved in motivational evaluation. These findings suggest that self-regulatory fatigability is associated with relatively less recruitment of prefrontal cortical regions involved in executive control.

Imagine All the People: How the Brain Creates and Uses Personality Models to Predict Behavior

PubMed Central

Hassabis, Demis; Spreng, R. Nathan; Rusu, Andrei A.; Robbins, Clifford A.; Mar, Raymond A.; Schacter, Daniel L.

2014-01-01

The behaviors of other people are often central to envisioning the future. The ability to accurately predict the thoughts and actions of others is essential for successful social interactions, with far-reaching consequences. Despite its importance, little is known about how the brain represents people in order to predict behavior. In this functional magnetic resonance imaging study, participants learned the unique personality of 4 protagonists and imagined how each would behave in different scenarios. The protagonists' personalities were composed of 2 traits: Agreeableness and Extraversion. Which protagonist was being imagined was accurately inferred based solely on activity patterns in the medial prefrontal cortex using multivariate pattern classification, providing novel evidence that brain activity can reveal whom someone is thinking about. Lateral temporal and posterior cingulate cortex discriminated between different degrees of agreeableness and extraversion, respectively. Functional connectivity analysis confirmed that regions associated with trait-processing and individual identities were functionally coupled. Activity during the imagination task, and revealed by functional connectivity, was consistent with the default network. Our results suggest that distinct regions code for personality traits, and that the brain combines these traits to represent individuals. The brain then uses this “personality model” to predict the behavior of others in novel situations. PMID:23463340

Hippocampal-prefrontal input supports spatial encoding in working memory.

PubMed

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

2015-06-18

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

The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

PubMed Central

Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

2013-01-01

This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

Parsing dimensional vs diagnostic category-related patterns of reward circuitry function in behaviorally and emotionally dysregulated youth in the Longitudinal Assessment of Manic Symptoms study.

PubMed

Bebko, Genna; Bertocci, Michele A; Fournier, Jay C; Hinze, Amanda K; Bonar, Lisa; Almeida, Jorge R C; Perlman, Susan B; Versace, Amelia; Schirda, Claudiu; Travis, Michael; Gill, Mary Kay; Demeter, Christine; Diwadkar, Vaibhav A; Ciuffetelli, Gary; Rodriguez, Eric; Olino, Thomas; Forbes, Erika; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2014-01-01

Pediatric disorders characterized by behavioral and emotional dysregulation pose diagnostic and treatment challenges because of high comorbidity, suggesting that they may be better conceptualized dimensionally rather than categorically. Identifying neuroimaging measures associated with behavioral and emotional dysregulation in youth may inform understanding of underlying dimensional vs disorder-specific pathophysiologic features. To identify, in a large cohort of behaviorally and emotionally dysregulated youth, neuroimaging measures that (1) are associated with behavioral and emotional dysregulation pathologic dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory 10-Item Mania Scale [PGBI-10M], mania, depression, and anxiety) or (2) differentiate diagnostic categories (bipolar spectrum disorders, attention-deficit/hyperactivity disorder, anxiety, and disruptive behavior disorders). A multisite neuroimaging study was conducted from February 1, 2011, to April 15, 2012, at 3 academic medical centers: University Hospitals Case Medical Center, Cincinnati Children's Hospital Medical Center, and University of Pittsburgh Medical Center. Participants included a referred sample of behaviorally and emotionally dysregulated youth from the Longitudinal Assessment of Manic Symptoms (LAMS) study (n = 85) and healthy youth (n = 20). Region-of-interest analyses examined relationships among prefrontal-ventral striatal reward circuitry during a reward paradigm (win, loss, and control conditions), symptom dimensions, and diagnostic categories. Regardless of diagnosis, higher PGBI-10M scores were associated with greater left middle prefrontal cortical activity (r = 0.28) and anxiety with greater right dorsal anterior cingulate cortical (r = 0.27) activity to win. The 20 highest (t = 2.75) and 20 lowest (t = 2.42) PGBI-10M-scoring youth showed significantly greater left middle prefrontal cortical activity to win compared with 20 healthy youth. Disruptive behavior disorders were associated with lower left ventrolateral prefrontal cortex activity to win (t = 2.68) (all P < .05, corrected). Greater PGBI-10M-related left middle prefrontal cortical activity and anxiety-related right dorsal anterior cingulate cortical activity to win may reflect heightened reward sensitivity and greater attention to reward in behaviorally and emotionally dysregulated youth regardless of diagnosis. Reduced left ventrolateral prefrontal cortex activity to win may reflect reward insensitivity in youth with disruptive behavior disorders. Despite a distinct reward-related neurophysiologic feature in disruptive behavior disorders, findings generally support a dimensional approach to studying neural mechanisms in behaviorally and emotionally dysregulated youth.

Neural mechanisms tracking popularity in real-world social networks

PubMed Central

Zerubavel, Noam; Bearman, Peter S.; Weber, Jochen; Ochsner, Kevin N.

2015-01-01

Differences in popularity are a key aspect of status in virtually all human groups and shape social interactions within them. Little is known, however, about how we track and neurally represent others’ popularity. We addressed this question in two real-world social networks using sociometric methods to quantify popularity. Each group member (perceiver) viewed faces of every other group member (target) while whole-brain functional MRI data were collected. Independent functional localizer tasks were used to identify brain systems supporting affective valuation (ventromedial prefrontal cortex, ventral striatum, amygdala) and social cognition (dorsomedial prefrontal cortex, precuneus, temporoparietal junction), respectively. During the face-viewing task, activity in both types of neural systems tracked targets’ sociometric popularity, even when controlling for potential confounds. The target popularity–social cognition system relationship was mediated by valuation system activity, suggesting that observing popular individuals elicits value signals that facilitate understanding their mental states. The target popularity–valuation system relationship was strongest for popular perceivers, suggesting enhanced sensitivity to differences among other group members’ popularity. Popular group members also demonstrated greater interpersonal sensitivity by more accurately predicting how their own personalities were perceived by other individuals in the social network. These data offer insights into the mechanisms by which status guides social behavior. PMID:26598684

Individualism, conservatism, and radicalism as criteria for processing political beliefs: a parametric fMRI study.

PubMed

Zamboni, Giovanna; Gozzi, Marta; Krueger, Frank; Duhamel, Jean-René; Sirigu, Angela; Grafman, Jordan

2009-01-01

Politics is a manifestation of the uniquely human ability to debate, decide, and reach consensus on decisions affecting large groups over long durations of time. Recent neuroimaging studies on politics have focused on the association between brain regions and specific political behaviors by adopting party or ideological affiliation as a criterion to classify either experimental stimuli or subjects. However, it is unlikely that complex political beliefs (i.e., "the government should protect freedom of speech") are evaluated only on a liberal-to-conservative criterion. Here we used multidimensional scaling and parametric functional magnetic resonance imaging to identify which criteria/dimensions people use to structure complex political beliefs and which brain regions are concurrently activated. We found that three independent dimensions explained the variability of a set of statements expressing political beliefs and that each dimension was reflected in a distinctive pattern of neural activation: individualism (medial prefrontal cortex and temporoparietal junction), conservatism (dorsolateral prefrontal cortex), and radicalism (ventral striatum and posterior cingulate). The structures we identified are also known to be important in self-other processing, social decision-making in ambivalent situations, and reward prediction. Our results extend current knowledge on the neural correlates of the structure of political beliefs, a fundamental aspect of the human ability to coalesce into social entities.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

PubMed

Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne

2015-06-30

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

Chang, Chun-Hui

2017-07-01

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

Prefrontal oxygenation correlates to the responses in facial skin blood flows during exposure to pleasantly charged movie.

PubMed

Matsukawa, Kanji; Endo, Kana; Asahara, Ryota; Yoshikawa, Miho; Kusunoki, Shinya; Ishida, Tomoko

2017-11-01

Our laboratory reported that facial skin blood flow may serve as a sensitive tool to assess an emotional status. Cerebral neural correlates during emotional interventions should be sought in relation to the changes in facial skin blood flow. To test the hypothesis that prefrontal activity has positive relation to the changes in facial skin blood flow during emotionally charged stimulation, we examined the dynamic changes in prefrontal oxygenation (with near-infrared spectroscopy) and facial skin blood flows (with two-dimensional laser speckle and Doppler flowmetry) during emotionally charged audiovisual challenges for 2 min (by viewing comedy, landscape, and horror movie) in 14 subjects. Hand skin blood flow and systemic hemodynamics were simultaneously measured. The extents of pleasantness and consciousness for each emotional stimulus were estimated by subjective rating from -5 (the most unpleasant; the most unconscious) to +5 (the most pleasant; the most conscious). Positively charged emotional stimulation (comedy) simultaneously decreased ( P  <   0.05) prefrontal oxygenation and facial skin blood flow, whereas negatively charged (horror) or neutral (landscape) emotional stimulation did not alter or slightly decreased them. Any of hand skin blood flow and systemic cardiovascular variables did not change significantly during positively charged emotional stimulation. The changes in prefrontal oxygenation had a highly positive correlation with the changes in facial skin blood flow without altering perfusion pressure, and they were inversely correlated with the subjective rating of pleasantness. The reduction in prefrontal oxygenation during positively charged emotional stimulation suggests a decrease in prefrontal neural activity, which may in turn elicit neurally mediated vasoconstriction of facial skin blood vessels. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.

PubMed

Tanaka, Tatsunori; Ago, Yukio; Umehara, Chiaki; Imoto, Emina; Hasebe, Shigeru; Hashimoto, Hitoshi; Takuma, Kazuhiro; Matsuda, Toshio

2017-05-01

Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice. To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days. The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron. The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression. © The Author 2016. Published by Oxford University Press on behalf of CINP.

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

PubMed

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

2015-02-01

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

The Function and Organization of Lateral Prefrontal Cortex: A Test of Competing Hypotheses

PubMed Central

Reynolds, Jeremy R.; O'Reilly, Randall C.; Cohen, Jonathan D.; Braver, Todd S.

2012-01-01

The present experiment tested three hypotheses regarding the function and organization of lateral prefrontal cortex (PFC). The first account (the information cascade hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the timing with which cue stimuli reduce uncertainty in the action selection process. The second account (the levels-of-abstraction hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the degree of abstraction of the task goals. The current study began by investigating these two hypotheses, and identified several areas of lateral PFC that were predicted to be active by both the information cascade and levels-of-abstraction accounts. However, the pattern of activation across experimental conditions was inconsistent with both theoretical accounts. Specifically, an anterior area of mid-dorsolateral PFC exhibited sensitivity to experimental conditions that, according to both accounts, should have selectively engaged only posterior areas of PFC. We therefore investigated a third possible account (the adaptive context maintenance hypothesis) that postulates that both posterior and anterior regions of PFC are reliably engaged in task conditions requiring active maintenance of contextual information, with the temporal dynamics of activity in these regions flexibly tracking the duration of maintenance demands. Activity patterns in lateral PFC were consistent with this third hypothesis: regions across lateral PFC exhibited transient activation when contextual information had to be updated and maintained in a trial-by-trial manner, but sustained activation when contextual information had to be maintained over a series of trials. These findings prompt a reconceptualization of current views regarding the anterior-posterior organization of lateral PFC, but do support other findings regarding the active maintenance role of lateral PFC in sequential working memory paradigms. PMID:22355309

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

PubMed

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

2015-06-01

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

The Spatial Release of Cognitive Load in Cocktail Party Is Determined by the Relative Levels of the Talkers.

PubMed

Andéol, Guillaume; Suied, Clara; Scannella, Sébastien; Dehais, Frédéric

2017-06-01

In a multi-talker situation, spatial separation between talkers reduces cognitive processing load: this is the "spatial release of cognitive load". The present study investigated the role played by the relative levels of the talkers on this spatial release of cognitive load. During the experiment, participants had to report the speech emitted by a target talker in the presence of a concurrent masker talker. The spatial separation (0° and 120° angular distance in azimuth) and the relative levels of the talkers (adverse, intermediate, and favorable target-to-masker ratio) were manipulated. The cognitive load was assessed with a prefrontal functional near-infrared spectroscopy. Data from 14 young normal-hearing listeners revealed that the target-to-masker ratio had a direct impact on the spatial release of cognitive load. Spatial separation significantly reduced the prefrontal activity only for the intermediate target-to-masker ratio and had no effect on prefrontal activity for the favorable and the adverse target-to-masker ratios. Therefore, the relative levels of the talkers might be a key point to determine the spatial release of cognitive load and more specifically the prefrontal activity induced by spatial cues in multi-talker situations.

The Predictive Brain State: Timing Deficiency in Traumatic Brain Injury?

PubMed Central

Ghajar, Jamshid; Ivry, Richard B.

2015-01-01

Attention and memory deficits observed in traumatic brain injury (TBI) are postulated to result from the shearing of white matter connections between the prefrontal cortex, parietal lobe, and cerebellum that are critical in the generation, maintenance, and precise timing of anticipatory neural activity. These fiber tracts are part of a neural network that generates predictions of future states and events, processes that are required for optimal performance on attention and working memory tasks. The authors discuss the role of this anticipatory neural system for understanding the varied symptoms and potential rehabilitation interventions for TBI. Preparatory neural activity normally allows the efficient integration of sensory information with goal-based representations. It is postulated that an impairment in the generation of this activity in traumatic brain injury (TBI) leads to performance variability as the brain shifts from a predictive to reactive mode. This dysfunction may constitute a fundamental defect in TBI as well as other attention disorders, causing working memory deficits, distractibility, a loss of goal-oriented behavior, and decreased awareness. “The future is not what is coming to meet us, but what we are moving forward to meet.” —Jean-Marie Guyau1 PMID:18460693

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

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.

Prefrontal brain asymmetry and pre-menstrual dysphoric disorder symptomatology.

PubMed

Accortt, Eynav E; Stewart, Jennifer L; Coan, James A; Manber, Rachel; Allen, John J B

2011-01-01

Pre-menstrual dysphoric disorder (PMDD), a dysphoric form of pre-menstrual syndrome, is included as a diagnosis for further study in the DSM-IV-TR (APA, 2000). The present study investigated whether a marker of risk for major depressive disorder (MDD), prefrontal brain asymmetry, also characterizes women with PMDD. In a sample of 25 college women with PMDD symptomatology and 25 matched controls, resting frontal electroencephalographic (EEG) activity was assessed on four occasions within a two-week span. Across several frontal sites women with PMDD had relatively less left than right prefrontal brain activity, consistent with a diathesis-stress model for menstrual-related dysphoria. The findings suggest an overlap in the risk profile for MDD and PMDD. Published by Elsevier B.V.

The role of left prefrontal cortex in language and memory

PubMed Central

Gabrieli, John D. E.; Poldrack, Russell A.; Desmond, John E.

1998-01-01

This article reviews attempts to characterize the mental operations mediated by left inferior prefrontal cortex, especially the anterior and inferior portion of the gyrus, with the functional neuroimaging techniques of positron emission tomography and functional magnetic resonance imaging. Activations in this region occur during semantic, relative to nonsemantic, tasks for the generation of words to semantic cues or the classification of words or pictures into semantic categories. This activation appears in the right prefrontal cortex of people known to be atypically right-hemisphere dominant for language. In this region, activations are associated with meaningful encoding that leads to superior explicit memory for stimuli and deactivations with implicit semantic memory (repetition priming) for words and pictures. New findings are reported showing that patients with global amnesia show deactivations in the same region associated with repetition priming, that activation in this region reflects selection of a response from among numerous relative to few alternatives, and that activations in a portion of this region are associated specifically with semantic relative to phonological processing. It is hypothesized that activations in left inferior prefrontal cortex reflect a domain-specific semantic working memory capacity that is invoked more for semantic than nonsemantic analyses regardless of stimulus modality, more for initial than for repeated semantic analysis of a word or picture, more when a response must be selected from among many than few legitimate alternatives, and that yields superior later explicit memory for experiences. PMID:9448258

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

PubMed Central

Luechinger, Roger; Boesiger, Peter; Rasch, Björn

2013-01-01

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks. PMID:23565239

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

PubMed

Ito, Jun; Fujiwara, Takeo; Monden, Yukifumi; Yamagata, Takanori; Ohira, Hideki

2017-01-01

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

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Cortical Dopamine Transmission as Measured with the [11C]FLB 457 – Amphetamine PET Imaging Paradigm Is Not Influenced by COMT Genotype

PubMed Central

Narendran, Rajesh; Tumuluru, Divya; May, Maureen A.; Chowdari, Kodavali V.; Himes, Michael L.; Fasenmyer, Kelli; Frankle, W. Gordon; Nimgaonkar, Vishwajit L.

2016-01-01

Basic investigations link a Val158Met polymorphism (rs4680) in the catechol-O-methyltransferase (COMT) gene to not only its enzymatic activity, but also to its dopaminergic tone in the prefrontal cortex. Previous PET studies have documented the relationship between COMT Val158Met polymorphism and D1 and D2/3 receptor binding potential (BP), and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D1 and D2/3 receptor binding potential (BPND) as a proxy for dopaminergic tone is problematic because they reflect both endogenous dopamine levels (a change in radiotracer's apparent affinity) and receptor density. In this analysis of 31 healthy controls genotyped for the Val158Met polymorphism (Val/Val, Val/Met, and Met/Met), we used amphetamine-induced displacement of [11C]FLB 457 as a direct measure of dopamine release. Our analysis failed to show a relationship between COMT genotype status and prefrontal cortical dopamine release. COMT genotype was also not predictive of baseline dopamine D2/3 receptor BPND. PMID:27322568

From Concrete Examples to Abstract Relations: The Rostrolateral Prefrontal Cortex Integrates Novel Examples into Relational Categories.

PubMed

Davis, Tyler; Goldwater, Micah; Giron, Josue

2017-04-01

The ability to form relational categories for objects that share few features in common is a hallmark of human cognition. For example, anything that can play a preventative role, from a boulder to poverty, can be a "barrier." However, neurobiological research has focused solely on how people acquire categories defined by features. The present functional magnetic resonance imaging study examines how relational and feature-based category learning compare in well-matched learning tasks. Using a computational model-based approach, we observed a cluster in left rostrolateral prefrontal cortex (rlPFC) that tracked quantitative predictions for the representational distance between test and training examples during relational categorization. Contrastingly, medial and dorsal PFC exhibited graded activation that tracked decision evidence during both feature-based and relational categorization. The results suggest that rlPFC computes an alignment signal that is critical for integrating novel examples during relational categorization whereas other PFC regions support more general decision functions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Perceived stress predicts altered reward and loss feedback processing in medial prefrontal cortex

PubMed Central

Treadway, Michael T.; Buckholtz, Joshua W.; Zald, David H.

2013-01-01

Stress is a significant risk factor for the development of psychopathology, particularly symptoms related to reward processing. Importantly, individuals display marked variation in how they perceive and cope with stressful events, and such differences are strongly linked to risk for developing psychiatric symptoms following stress exposure. However, many questions remain regarding the neural architecture that underlies inter-subject variability in perceptions of stressors. Using functional magnetic resonance imaging (fMRI) during a Monetary Incentive Delay (MID) paradigm, we examined the effects of self-reported perceived stress levels on neural activity during reward anticipation and feedback in a sample of healthy individuals. We found that subjects reporting more uncontrollable and overwhelming stressors displayed blunted neural responses in medial prefrontal cortex (mPFC) following feedback related to monetary gains as well monetary losses. This is consistent with preclinical models that implicate the mPFC as a key site of vulnerability to the noxious effects of uncontrollable stressors. Our data help translate these findings to humans, and elucidate some of the neural mechanisms that may underlie stress-linked risk for developing reward-related psychiatric symptoms. PMID:23730277

Differential representation of Pavlovian-instrumental transfer by prefrontal cortex subregions and striatum.

PubMed

Homayoun, Houman; Moghaddam, Bita

2009-04-01

Environmental cues that once predicted reward can restore extinguished behavior directed toward that reward. This process may be modeled by the Pavlovian-instrumental transfer (PIT) paradigm where a previously learned Pavlovian conditioned stimulus (CS) elicits a representation of the reward associated with that CS, prompts motivation toward the absent reward, and triggers an instrumental action. We recorded in the medial and orbital prefrontal cortex (mPFC and OFC) and dorsal striatum (DS) of freely moving rats during PIT and found that a Pavlovian CS, as compared with neutral or no stimuli, amplified the phasic neuronal responses to instrumental nosepokes ('transfer' event). In mPFC and OFC, but not the DS, representation of the transfer event correlated with the strength of PIT behavior. Neurons in all three regions showed CS-selective amplification of Pavlovian approaches toward the reward delivery site. Whereas striatal neurons represented transfer and approach behavior through mostly segregated neuronal subsets, overlapping subsets represented these events in the mPFC and OFC. These findings suggest that parallel phasic activation of mPFC and OFC neuronal subsets participates in the transfer from Pavlovian incentives to instrumental actions.

EEG oscillations during sleep and dream recall: state- or trait-like individual differences?

PubMed Central

Scarpelli, Serena; D’Atri, Aurora; Gorgoni, Maurizio; Ferrara, Michele; De Gennaro, Luigi

2015-01-01

Dreaming represents a peculiar form of cognitive activity during sleep. On the basis of the well-known relationship between sleep and memory, there has been a growing interest in the predictive role of human brain activity during sleep on dream recall. Neuroimaging studies indicate that rapid eye movement (REM) sleep is characterized by limbic activation and prefrontal cortex deactivation. This pattern could explain the presence of emotional contents in dream reports. Furthermore, the morphoanatomical measures of amygdala and hippocampus predict some features of dream contents (bizarreness, vividness, and emotional load). More relevant for a general view of dreaming mechanisms, empirical data from neuropsychological and electroencephalographic (EEG) studies support the hypothesis that there is a sort of continuity between the neurophysiological mechanisms of encoding and retrieval of episodic memories across sleep and wakefulness. A notable overlap between the electrophysiological mechanisms underlying emotional memory formation and some peculiar EEG features of REM sleep has been suggested. In particular, theta (5–8 Hz) EEG oscillations on frontal regions in the pre-awakening sleep are predictive of dream recall, which parallels the predictive relation during wakefulness between theta activity and successful retrieval of episodic memory. Although some observations support an interpretation more in terms of an intraindividual than interindividual mechanism, the existing empirical evidence still precludes from definitely disentangling if this relation is explained by state- or trait-like differences. PMID:25999908

Sex differences in structural brain asymmetry predict overt aggression in early adolescents.

PubMed

Visser, Troy A W; Ohan, Jeneva L; Whittle, Sarah; Yücel, Murat; Simmons, Julian G; Allen, Nicholas B

2014-04-01

The devastating social, emotional and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e. left vs right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here, we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.

Contextual Processing of Abstract Concepts Reveals Neural Representations of Non-Linguistic Semantic Content

PubMed Central

Wilson-Mendenhall, Christine D.; Simmons, W. Kyle; Martin, Alex; Barsalou, Lawrence W.

2014-01-01

Concepts develop for many aspects of experience, including abstract internal states and abstract social activities that do not refer to concrete entities in the world. The current study assessed the hypothesis that, like concrete concepts, distributed neural patterns of relevant, non-linguistic semantic content represent the meanings of abstract concepts. In a novel neuroimaging paradigm, participants processed two abstract concepts (convince, arithmetic) and two concrete concepts (rolling, red) deeply and repeatedly during a concept-scene matching task that grounded each concept in typical contexts. Using a catch trial design, neural activity associated with each concept word was separated from neural activity associated with subsequent visual scenes to assess activations underlying the detailed semantics of each concept. We predicted that brain regions underlying mentalizing and social cognition (e.g., medial prefrontal cortex, superior temporal sulcus) would become active to represent semantic content central to convince, whereas brain regions underlying numerical cognition (e.g., bilateral intraparietal sulcus) would become active to represent semantic content central to arithmetic. The results supported these predictions, suggesting that the meanings of abstract concepts arise from distributed neural systems that represent concept-specific content. PMID:23363408

Measuring emotion in advertising research: prefrontal brain activity.

PubMed

Silberstein, Richard B; Nield, Geoffrey E

2012-01-01

With the current interest in the role of emotion in advertising and advertising research, there has been an increasing interest in the use of various brain activity measures to access nonverbal emotional responses. One such approach relies on measuring the difference between left and right hemisphere prefrontal cortical activity to assess like and dislike. This approach is based on electroencephalography (EEG) and neuroimaging work, suggesting that the approach/withdrawal (frequently but not always associated with like/dislike) dimension of emotion is indicated by the balance of activity between the left and right prefrontal cortex. Much of this work was initiated by Richard Davidson in the early 1990s. An early study by Davidson et al. measured brain electrical activity to assess patterns of activation during the experience of happiness and disgust. The authors reported that disgust was found to be associated with increased right-sided activation in the frontal and anterior temporal regions compared with happiness. In contrast, happiness was found to be accompanied by left-sided activation in the anterior temporal region compared with disgust. Early reports suggested that frontal laterality indexes motivational valence with positive emotions (happy, like) associated with left greater than the right frontal activity and vice versa. Although these findings appear to be consistent with personality traits (e.g., optimism pessimism), state changes in frontal laterality appears to index approach withdraw rather than emotional valence. Interestingly, the behavioral and motivational correlates of prefrontal asymmetric activity are not restricted to humans or even primates but have been observed in numerous species such as birds and fish (see [4]). Henceforth, we use the term motivational valence (MV) rather than the more cumbersome term approach withdraw.