Visual Predictions in the Orbitofrontal Cortex Rely on Associative Content

PubMed Central

Chaumon, Maximilien; Kveraga, Kestutis; Barrett, Lisa Feldman; Bar, Moshe

2014-01-01

Predicting upcoming events from incomplete information is an essential brain function. The orbitofrontal cortex (OFC) plays a critical role in this process by facilitating recognition of sensory inputs via predictive feedback to sensory cortices. In the visual domain, the OFC is engaged by low spatial frequency (LSF) and magnocellular-biased inputs, but beyond this, we know little about the information content required to activate it. Is the OFC automatically engaged to analyze any LSF information for meaning? Or is it engaged only when LSF information matches preexisting memory associations? We tested these hypotheses and show that only LSF information that could be linked to memory associations engages the OFC. Specifically, LSF stimuli activated the OFC in 2 distinct medial and lateral regions only if they resembled known visual objects. More identifiable objects increased activity in the medial OFC, known for its function in affective responses. Furthermore, these objects also increased the connectivity of the lateral OFC with the ventral visual cortex, a crucial region for object identification. At the interface between sensory, memory, and affective processing, the OFC thus appears to be attuned to the associative content of visual information and to play a central role in visuo-affective prediction. PMID:23771980

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

5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

PubMed

Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

2017-03-01

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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…

Brain, emotion and decision making: the paradigmatic example of regret.

PubMed

Coricelli, Giorgio; Dolan, Raymond J; Sirigu, Angela

2007-06-01

Human decisions cannot be explained solely by rational imperatives but are strongly influenced by emotion. Theoretical and behavioral studies provide a sound empirical basis to the impact of the emotion of regret in guiding choice behavior. Recent neuropsychological and neuroimaging data have stressed the fundamental role of the orbitofrontal cortex in mediating the experience of regret. Functional magnetic resonance imaging data indicate that reactivation of activity within the orbitofrontal cortex and amygdala occurring during the phase of choice, when the brain is anticipating possible future consequences of decisions, characterizes the anticipation of regret. In turn, these patterns reflect learning based on cumulative emotional experience. Moreover, affective consequences can induce specific mechanisms of cognitive control of the choice processes, involving reinforcement or avoidance of the experienced behavior.

Decision-making performance in Parkinson's disease correlates with lateral orbitofrontal volume.

PubMed

Kobayakawa, Mutsutaka; Tsuruya, Natsuko; Kawamura, Mitsuru

2017-01-15

Patients with Parkinson's disease (PD) exhibit poor decision-making, and the underlying neural correlates are unclear. We used voxel-based morphometry with Diffeomorphic Anatomical Registration through Exponentiated Lie algebra to examine this issue. The decision-making abilities of 20 patients with PD and 37 healthy controls (HCs) were measured with a computerized Iowa Gambling Task (IGT). We assessed the local gray matter volumes of the patients and HCs and their correlations with decision-making performance, disease duration, disease severity, and anti-Parkinsonism medication dose. Compared with the HCs, the patients with PD exhibited poor IGT performances. The gray matter volumes in the medial orbitofrontal cortex, left inferior temporal cortex, and right middle frontal gyrus were decreased in the patients. Results in the regression analysis showed that lateral orbitofrontal volume correlated with performance in the IGT in PD. Regions that correlated with disease duration, severity, and medication dose did not overlap with orbitofrontal regions. Our results indicate that the lateral and medial orbitofrontal cortex are related to decision-making in PD patients. Since the medial orbitofrontal cortex is shown to be involved in monitoring reward, reward monitoring seems to be impaired as a whole in PD patients. Meanwhile, the lateral region is related to evaluation of punishment, which is considered to have an influence on individual differences in decision-making performance in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Reduced amygdala-orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits

PubMed Central

Marsh, Abigail A.; Finger, Elizabeth C.; Fowler, Katherine A.; Jurkowitz, Ilana T.N.; Schechter, Julia C.; Yu, Henry H.; Pine, Daniel S.; Blair, R. J. R.

2011-01-01

We used functional magnetic resonance imaging (fMRI) to investigate dysfunction in the amygdala and orbitofrontal cortex in adolescents with disruptive behavior disorders and psychopathic traits during a moral judgment task. Fourteen adolescents with psychopathic traits and 14 healthy controls were assessed using fMRI while they categorized illegal and legal behaviors in a moral judgment implicit association task. fMRI data were then analyzed using random-effects analysis of variance and functional connectivity. Youths with psychopathic traits showed reduced amygdala activity when making judgments about legal actions and reduced functional connectivity between the amygdala and orbitofrontal cortex during task performance. These results suggest that psychopathic traits are associated with amygdala and orbitofrontal cortex dysfunction. This dysfunction may relate to previous findings of disrupted moral judgment in this population. PMID:22047730

Differential involvement of the basolateral amygdala and orbitofrontal cortex in the formation of sensory-specific associations in conditioned flavor preference and magazine approach paradigms.

PubMed

Scarlet, Janina; Delamater, Andrew R; Campese, Vincent; Fein, Matthew; Wheeler, Daniel S

2012-06-01

Four experiments examined the roles of the basolateral amygdala and orbitofrontal cortex in the formation of sensory-specific associations in conditioned flavor preference and conditioned magazine approach paradigms using unconditioned stimulus (US) devaluation and selective Pavlovian-instrumental transfer procedures in Long Evans rats. Experiment 1 found that pre-training amygdala and orbitofrontal cortex lesions had no detectable effect on the formation or flexible use of sensory-specific flavor-nutrient associations in a US devaluation task, where flavor cues were paired either simultaneously or sequentially with nutrient rewards in water-deprived subjects. In Experiment 2, pre-training amygdala and orbitofrontal cortex lesions both attenuated outcome-specific Pavlovian-instrumental transfer. Experiment 3 indicated that amygdala lesions have no effect on the formation of sensory-specific flavor-nutrient associations in a US devaluation task in food-deprived subjects. Finally, Experiment 4 demonstrated that the outcomes used in Experiment 3 were sufficiently motivationally significant to support conditioned flavor preference. These findings suggest that, although both orbitofrontal cortex and amygdala lesions attenuate the acquisition of sensory-specific associations in magazine approach conditioning, neither lesion reduces the ability to appropriately respond to a flavor cue that was paired with a devalued outcome. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Affective network and default mode network in depressive adolescents with disruptive behaviors

PubMed Central

Kim, Sun Mi; Park, Sung Yong; Kim, Young In; Son, Young Don; Chung, Un-Sun; Min, Kyung Joon; Han, Doug Hyun

2016-01-01

Aim Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD) in adolescents. In resting-state functional connectivity (RSFC) studies of MDD, the affective network (limbic network) and the default mode network (DMN) have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors. Methods Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD) and 20 age- and sex-matched healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC) for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors. Results The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively correlated with RSFC from the PCC to the left insular cortex. Conclusion Depressive mood might be correlated with the affective network, and disruptive behavior might be correlated with the DMN in adolescent depression. PMID:26770059

Spike-Timing of Orbitofrontal Neurons Is Synchronized With Breathing.

PubMed

Kőszeghy, Áron; Lasztóczi, Bálint; Forro, Thomas; Klausberger, Thomas

2018-01-01

The orbitofrontal cortex (OFC) has been implicated in a multiplicity of complex brain functions, including representations of expected outcome properties, post-decision confidence, momentary food-reward values, complex flavors and odors. As breathing rhythm has an influence on odor processing at primary olfactory areas, we tested the hypothesis that it may also influence neuronal activity in the OFC, a prefrontal area involved also in higher order processing of odors. We recorded spike timing of orbitofrontal neurons as well as local field potentials (LFPs) in awake, head-fixed mice, together with the breathing rhythm. We observed that a large majority of orbitofrontal neurons showed robust phase-coupling to breathing during immobility and running. The phase coupling of action potentials to breathing was significantly stronger in orbitofrontal neurons compared to cells in the medial prefrontal cortex. The characteristic synchronization of orbitofrontal neurons with breathing might provide a temporal framework for multi-variable processing of olfactory, gustatory and reward-value relationships.

Disentangling neural representations of value and salience in the human brain

PubMed Central

Kahnt, Thorsten; Park, Soyoung Q; Haynes, John-Dylan; Tobler, Philippe N.

2014-01-01

A large body of evidence has implicated the posterior parietal and orbitofrontal cortex in the processing of value. However, value correlates perfectly with salience when appetitive stimuli are investigated in isolation. Accordingly, considerable uncertainty has remained about the precise nature of the previously identified signals. In particular, recent evidence suggests that neurons in the primate parietal cortex signal salience instead of value. To investigate neural signatures of value and salience, here we apply multivariate (pattern-based) analyses to human functional MRI data acquired during a noninstrumental outcome-prediction task involving appetitive and aversive outcomes. Reaction time data indicated additive and independent effects of value and salience. Critically, we show that multivoxel ensemble activity in the posterior parietal cortex encodes predicted value and salience in superior and inferior compartments, respectively. These findings reinforce the earlier reports of parietal value signals and reconcile them with the recent salience report. Moreover, we find that multivoxel patterns in the orbitofrontal cortex correlate with value. Importantly, the patterns coding for the predicted value of appetitive and aversive outcomes are similar, indicating a common neural scale for appetite and aversive values in the orbitofrontal cortex. Thus orbitofrontal activity patterns satisfy a basic requirement for a neural value signal. PMID:24639493

Reduced amygdala-orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits.

PubMed

Marsh, Abigail A; Finger, Elizabeth C; Fowler, Katherine A; Jurkowitz, Ilana T N; Schechter, Julia C; Yu, Henry H; Pine, Daniel S; Blair, R J R

2011-12-30

We used functional magnetic resonance imaging (fMRI) to investigate dysfunction in the amygdala and orbitofrontal cortex in adolescents with disruptive behavior disorders and psychopathic traits during a moral judgment task. Fourteen adolescents with psychopathic traits and 14 healthy controls were assessed using fMRI while they categorized illegal and legal behaviors in a moral judgment implicit association task. fMRI data were then analyzed using random-effects analysis of variance and functional connectivity. Youths with psychopathic traits showed reduced amygdala activity when making judgments about legal actions and reduced functional connectivity between the amygdala and orbitofrontal cortex during task performance. These results suggest that psychopathic traits are associated with amygdala and orbitofrontal cortex dysfunction. This dysfunction may relate to previous findings of disrupted moral judgment in this population. 2011 Elsevier Ireland Ltd. All rights reserved.

Emotion disrupts neural activity during selective attention in psychopathy

PubMed Central

Spielberg, Jeffrey M.; Heller, Wendy; Herrington, John D.; Engels, Anna S.; Warren, Stacie L.; Crocker, Laura D.; Sutton, Bradley P.; Miller, Gregory A.

2013-01-01

Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes. PMID:22210673

Emotion disrupts neural activity during selective attention in psychopathy.

PubMed

Sadeh, Naomi; Spielberg, Jeffrey M; Heller, Wendy; Herrington, John D; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

2013-03-01

Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes.

Neurocognitive Elements of Antisocial Behavior: Relevance of an Orbitofrontal Cortex Account

ERIC Educational Resources Information Center

Seguin, Jean R.

2004-01-01

This paper reviews the role of orbitofrontal cortex (OFC) lesions in antisocial behaviors and the adequacy of a strict OFC account of antisocial disorders where there is no evidence of lesion. Neurocognitive accounts of antisocial behaviors are extended beyond the OFC. Several methodological shortcomings specific to this neuroscience approach to…

Orbito-Frontal Cortex Is Necessary for Temporal Context Memory

ERIC Educational Resources Information Center

Duarte, Audrey; Henson, Richard N.; Knight, Robert T.; Emery, Tina; Graham, Kim S.

2010-01-01

Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two…

Behavioral and neurophysiological correlates of regret in rat decision-making on a neuroeconomic task

PubMed Central

Steiner, Adam P.; Redish, A. David

2014-01-01

Summary Disappointment entails the recognition that one did not get the value one expected. In contrast, regret entails the recognition that an alternate (counterfactual) action would have produced a more valued outcome. Thus, the key to identifying regret is the representation of that counterfactual option in situations in which a mistake has been made. In humans, the orbitofrontal cortex is active during expressions of regret, and humans with damage to the orbitofrontal cortex do not express regret. In rats and non-human primates, both the orbitofrontal cortex and the ventral striatum have been implicated in decision-making, particularly in representations of expectations of reward. In order to examine representations of regretful situations, we recorded neural ensembles from orbitofrontal cortex and ventral striatum in rats encountering a spatial sequence of wait/skip choices for delayed delivery of different food flavors. We were able to measure preferences using an economic framework. Rats occasionally skipped low-cost choices and then encountered a high-cost choice. This sequence economically defines a potential regret-inducing instance. In these situations, rats looked backwards towards the lost option, the cells within the orbitofrontal cortex and ventral striatum represented that missed action, rats were more likely to wait for the long delay, and rats rushed through eating the food after that delay. That these situations drove rats to modify their behavior suggests that regret-like processes modify decision-making in non-human mammals. PMID:24908102

Disentangling Depression and Distress Networks in the Tinnitus Brain

PubMed Central

Joos, Kathleen; Vanneste, Sven; De Ridder, Dirk

2012-01-01

Tinnitus is the continuous perception of an internal auditory stimulus. This permanent sound often affects a person's emotional state inducing distress and depressive feelings changes in 6–25% of the affected population. Distress and depression are two distinct emotional states. Whereas distress describes a transient aversive state, interfering with a person's ability to adequately adapt to stressors, depressive feelings should rather be considered as a more constant emotional state. Based on previous observations in chronic pain, posttraumatic stress disorder and depression, we assume that both states are related to separate neural circuits. We used the Dutch version of the Tinnitus Questionnaire to assess the global index of distress together with the Beck Depression Inventory to evaluate the depressive symptoms accompanying tinnitus. Furthermore sLORETA analysis was performed to correlate current density distribution with distress and depression scores, revealing a lateralization effect of depression versus distress. Distress is mainly correlated with alpha 2, beta 1 and beta 2 activity of the right frontopolar cortex and orbitofrontal cortex in combination with beta 2 activation of the anterior cingulate cortex. In contrast, the more permanent depressive alterations induced by tinnitus are associated with activity of alpha 2 activity in the left frontopolar and orbitofrontal cortex. These specific neural circuits are embedded in a greater neural network, with the parahippocampal region functioning as a crucial linkage between both tinnitus related pathways. PMID:22808188

Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

PubMed

Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

2016-11-01

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

Oscillations in human orbitofrontal cortex during even chance gambling.

PubMed

Kahn, Kevin; Kerr, Matthew S D; Park, Hyun-Joo; Thompson, Susan; Bulacio, Juan; Gonzalez-Martinez, Jorge; Sarma, Sridevi V; Gale, John

2014-01-01

Evaluating value and risk as well as comparing expected and actual outcomes is the crux of decision making and reinforcement based learning. In this study, we record from stereotactic electroencephalograph depth electrodes in a human subject in numerous areas in the brain. We focus on the lateral and medial orbitofrontal cortex while they perform a gambling task involving betting on a high card. Preliminary time-frequency analysis shows modulations in the 5-15 Hz band that is well synced to the different events of the task. These oscillations increase in both high betting scenarios as well as in losing scenarios though their effects cannot be decoupled. However, the activity between lateral and medial orbitofrontal cortex is a lot more homogenous than previously seen. Additionally, the timing of some of these oscillations occurs before even a response in the visual cortex. This evidence hints that these areas encode priors that influence our decision in future statistically ambiguous scenarios.

Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

PubMed Central

Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.

2013-01-01

Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior based on changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining brain regions contributing to the encoding, maintenance and retrieval of overlapping identity information during working memory using a delayed match-to-sample (DMS) task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the non-overlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and non-overlapping condition at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the DMS task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory while the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses. PMID:23640112

Neural Coding of Reward Magnitude in the Orbitofrontal Cortex of the Rat during a Five-Odor Olfactory Discrimination Task

ERIC Educational Resources Information Center

van Duuren, Esther; Nieto Escamez, Francisco A.; Joosten, Ruud N. J. M. A.; Visser, Rein; Mulder, Antonius B.; Pennartz, Cyriel M. A.

2007-01-01

The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory…

Acetylcholine in the Orbitofrontal Cortex Is Necessary for the Acquisition of a Socially Transmitted Food Preference

ERIC Educational Resources Information Center

Ross, Robert S.; McGaughy, Jill; Eichenbaum, Howard

2005-01-01

The social transmission of food preference task (STFP) has been used to examine the involvement of the hippocampus in learning and memory for a natural odor-odor association. However, cortical involvement in STFP has not been extensively studied. The orbitofrontal cortex (OFC) is important in odor-guided learning, and cholinergic depletion of the…

Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

PubMed

Mitchell, D G V; Fine, C; Richell, R A; Newman, C; Lumsden, J; Blair, K S; Blair, R J R

2006-05-01

Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. Copyright (c) 2006 APA, all rights reserved.

The neural substrates of in-group bias: a functional magnetic resonance imaging investigation.

PubMed

Van Bavel, Jay J; Packer, Dominic J; Cunningham, William A

2008-11-01

Classic minimal-group studies found that people arbitrarily assigned to a novel group quickly display a range of perceptual, affective, and behavioral in-group biases. We randomly assigned participants to a mixed-race team and used functional magnetic resonance imaging to identify brain regions involved in processing novel in-group and out-group members independently of preexisting attitudes, stereotypes, or familiarity. Whereas previous research on intergroup perception found amygdala activity--typically interpreted as negativity--in response to stigmatized social groups, we found greater activity in the amygdala, fusiform gyri, orbitofrontal cortex, and dorsal striatum when participants viewed novel in-group faces than when they viewed novel out-group faces. Moreover, activity in orbitofrontal cortex mediated the in-group bias in self-reported liking for the faces. These in-group biases in neural activity were not moderated by race or by whether participants explicitly attended to team membership or race, a finding suggesting that they may occur automatically. This study helps clarify the role of neural substrates involved in perceptual and affective in-group biases.

Trait self-esteem and neural activities related to self-evaluation and social feedback

PubMed Central

Yang, Juan; Xu, Xiaofan; Chen, Yu; Shi, Zhenhao; Han, Shihui

2016-01-01

Self-esteem has been associated with neural responses to self-reflection and attitude toward social feedback but in different brain regions. The distinct associations might arise from different tasks or task-related attitudes in the previous studies. The current study aimed to clarify these by investigating the association between self-esteem and neural responses to evaluation of one’s own personality traits and of others’ opinion about one’s own personality traits. We scanned 25 college students using functional MRI during evaluation of oneself or evaluation of social feedback. Trait self-esteem was measured using the Rosenberg self-esteem scale after scanning. Whole-brain regression analyses revealed that trait self-esteem was associated with the bilateral orbitofrontal activity during evaluation of one’s own positive traits but with activities in the medial prefrontal cortex, posterior cingulate, and occipital cortices during evaluation of positive social feedback. Our findings suggest that trait self-esteem modulates the degree of both affective processes in the orbitofrontal cortex during self-reflection and cognitive processes in the medial prefrontal cortex during evaluation of social feedback. PMID:26842975

Trait self-esteem and neural activities related to self-evaluation and social feedback.

PubMed

Yang, Juan; Xu, Xiaofan; Chen, Yu; Shi, Zhenhao; Han, Shihui

2016-02-04

Self-esteem has been associated with neural responses to self-reflection and attitude toward social feedback but in different brain regions. The distinct associations might arise from different tasks or task-related attitudes in the previous studies. The current study aimed to clarify these by investigating the association between self-esteem and neural responses to evaluation of one's own personality traits and of others' opinion about one's own personality traits. We scanned 25 college students using functional MRI during evaluation of oneself or evaluation of social feedback. Trait self-esteem was measured using the Rosenberg self-esteem scale after scanning. Whole-brain regression analyses revealed that trait self-esteem was associated with the bilateral orbitofrontal activity during evaluation of one's own positive traits but with activities in the medial prefrontal cortex, posterior cingulate, and occipital cortices during evaluation of positive social feedback. Our findings suggest that trait self-esteem modulates the degree of both affective processes in the orbitofrontal cortex during self-reflection and cognitive processes in the medial prefrontal cortex during evaluation of social feedback.

Neural evidence for reduced apprehensiveness of familiarized stimuli in a mere exposure paradigm.

PubMed

Zebrowitz, Leslie A; Zhang, Yi

2012-07-01

Mere familiarization with a stimulus increases liking for it or similar stimuli ("mere exposure" effects) as well as perceptual fluency, indexed by the speed and accuracy of categorizing it or similar stimuli ("priming" effects). Candidate mechanisms proposed to explain mere exposure effects include both increased positive affect associated with greater perceptual fluency, and reduced negative affect associated with diminished apprehensiveness of novel stimuli. Although these two mechanisms are not mutually exclusive, it is difficult for behavioral measures to disentangle them, since increased liking or other indices of greater positive affect toward exposed stimuli could result from increases in positive feelings or decreases in negative feelings or both. The present study sought to clarify this issue by building on research showing a dissociation at the neural level in which the lateral orbitofrontal cortex (LOFC) is activated more by negatively valenced than by neutral or positively valenced stimuli, with the reverse effect for medial orbitofrontal cortex (MOFC). Supporting the reduced apprehensiveness hypothesis, we found lower LOFC activation to familiarized faces and objects (repetition suppression). We did not find evidence to support the positive affect hypothesis in increased activation to familiarized stimuli in MOFC or in other parts of the reward circuit that respond more to positively valenced stimuli (repetition enhancement), although enhancement effects were shown in some regions.

Inducing Negative Affect Increases the Reward Value of Appetizing Foods in Dieters

PubMed Central

Wagner, Dylan D.; Boswell, Rebecca G.; Kelley, William M.; Heatherton, Todd F.

2013-01-01

Experiencing negative affect frequently precedes lapses in self-control for dieters, smokers, and drug addicts. Laboratory research has similarly shown that inducing negative emotional distress increases the consumption of food or drugs. One hypothesis for this finding is that emotional distress sensitizes the brain’s reward system to appetitive stimuli. Using functional neuroimaging, we demonstrate that inducing negative affect in chronic dieters increases activity in brain regions representing the reward value of appetitive stimuli when viewing appetizing food cues. Thirty female chronic dieters were randomly assigned to receive either a negative (n = 15) or neutral mood induction (n = 15) immediately followed by exposure to images of appetizing foods and natural scenes during functional magnetic resonance imaging (fMRI). Compared to chronic dieters in a neutral mood, those receiving a negative mood induction showed increased activity in the orbitofrontal cortex to appetizing food images. In addition, activity to food images in the orbitofrontal cortex and ventral striatum was correlated with individual differences in the degree to which the negative mood induction decreased participants’ self-esteem. These findings suggest that distress sensitizes the brain’s reward system to appetitive cues thereby offering a mechanism for the oft-observed relationship between negative affect and disinhibited eating. PMID:22524295

Tailored unilobar and multilobar resections for orbitofrontal-plus epilepsy.

PubMed

Serletis, Demitre; Bulacio, Juan; Alexopoulos, Andreas; Najm, Imad; Bingaman, William; González-Martínez, Jorge

2014-10-01

Surgery for frontal lobe epilepsy often has poor results, likely because of incomplete resection of the epileptogenic zone. To present our experience with a series of patients manifesting 2 different anatomo-electro-clinical patterns of refractory orbitofrontal epilepsy, necessitating different surgical approaches for resection in each group. Eleven patients with refractory epilepsy involving the orbitofrontal region were consecutively identified over 3 years in whom stereoelectroencephalography identified the epileptogenic zone. All patients underwent preoperative evaluation, stereoelectroencephalography, and postoperative magnetic resonance imaging. Demographic features, seizure semiology, imaging characteristics, location of the epileptogenic zone, surgical resection site, and pathological diagnosis were analyzed. Surgical outcome was correlated with type of resection. Five patients exhibited orbitofrontal plus frontal epilepsy with the epileptogenic zone consistently residing in the frontal lobe; after surgery, 4 patients were free of disabling seizures (Engel I) and 1 patient improved (Engel II). The remaining 6 patients had multilobar epilepsy with the epileptogenic zone located in the orbitofrontal cortex associated with the temporal polar region (orbitofrontal plus temporal polar epilepsy). After surgery, all 6 patients were free of disabling seizures (Engel I). Pathology confirmed focal cortical dysplasia in all patients. We report no complications or mortalities in this series. Our findings highlight the importance of differentiating between orbitofrontal plus frontal and orbitofrontal plus temporal polar epilepsy in patients afflicted with seizures involving the orbitofrontal cortex. For identified cases of orbitofrontal plus temporal polar epilepsy, a multilobar resection including the temporal pole may lead to improved postoperative outcomes with minimal morbidity or mortality.

Relative hyperperfusion by SPECT in a family with a presenilin 1 (T245P) mutation.

PubMed

Edwards-Lee, Terri; Wen, Johnny; Chung, Julia A; Vasinrapee, Panukorn; Mishkin, Frederick S

2008-01-01

Clinical characteristics of autosomal dominant Alzheimer's disease often differ clinically from sporadic disease with the onset of seizures, spasticity and myoclonus early in the disease course. Similarly imaging characteristics may also differ. We report the findings of relative hyperperfusion by Tc-99m HMPAO SPECT in the medial orbitofrontal cortex and anterior temporal lobe in four affected family members carrying a presenilin 1 mutation. SPECT of the four individuals was compared to an age-matched normal database. We speculate that the findings of relative medial orbitofrontal and anterior temporal lobe hyperperfusion may be a marker of early onset Alzheimer's disease in this family.

Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis

PubMed Central

Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

2016-01-01

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive–emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction. PMID:27801897

Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

PubMed

Schoenbaum, Geoffrey; Setlow, Barry; Saddoris, Michael P; Gallagher, Michela

2006-03-01

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

Face-selective and auditory neurons in the primate orbitofrontal cortex.

PubMed

Rolls, Edmund T; Critchley, Hugo D; Browning, Andrew S; Inoue, Kazuo

2006-03-01

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2-13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130-220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.

Cooperative interactions between hippocampal and striatal systems support flexible navigation

PubMed Central

Brown, Thackery I; Ross, Robert S; Tobyne, Sean M; Stern, Chantal E

2012-01-01

Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually-dependent navigation. PMID:22266411

Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal.

PubMed

Albein-Urios, Natalia; Verdejo-Román, Juan; Soriano-Mas, Carles; Asensio, Samuel; Martínez-González, José Miguel; Verdejo-García, Antonio

2013-12-01

Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Taste, olfactory, and food reward value processing in the brain.

PubMed

Rolls, Edmund T

2015-04-01

Complementary neuronal recordings in primates, and functional neuroimaging in humans, show that the primary taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture (including fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in a second tier of processing, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by associative learning with olfactory and visual inputs, and these neurons encode food reward value on a continuous scale in that they only respond to food when hungry, and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions, and selective attention to affective value, modulate the representation of the reward value of taste and olfactory stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex, a tertiary taste cortical area. The food reward representations formed in this way play an important role in the control of appetite, and food intake. Individual differences in these reward representations may contribute to obesity, and there are age-related differences in these value representations that shape the foods that people in different age groups find palatable. In a third tier of processing in medial prefrontal cortex area 10, decisions between stimuli of different reward value are taken, by attractor decision-making networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder

PubMed Central

Huey, Edward D.; Zahn, Roland; Krueger, Frank; Moll, Jorge; Kapogiannis, Dimitrios; Wassermann, Eric M.; Grafman, Jordan

2009-01-01

Imaging, surgical, and lesion studies suggest that the prefrontal cortex (orbitofrontal and anterior cingulate cortexes), basal ganglia, and thalamus are involved in the pathogenesis of obsessive-compulsive disorder (OCD). On the basis of these findings several models of OCD have been developed, but have had difficulty fully integrating the psychological and neuroanatomical findings of OCD. Recent research in the field of cognitive neuroscience on the normal function of these brain areas demonstrates the role of the orbitofrontal cortex in reward, the anterior cingulate cortex in error detection, the basal ganglia in affecting the threshold for activation of motor and behavioral programs, and the prefrontal cortex in storing memories of behavioral sequences (called “structured event complexes” or SECs). The authors propose that the initiation of these SECs can be accompanied by anxiety that is relieved with completion of the SEC, and that a deficit in this process could be responsible for many of the symptoms of OCD. Specifically, the anxiety can form the basis of an obsession, and a compulsion can be an attempt to receive relief from the anxiety by repeating parts of, or an entire, SEC. The authors discuss empiric support for, and specific experimental predictions of, this model. The authors believe that this model explains the specific symptoms, and integrates the psychology and neuroanatomy of OCD better than previous models. PMID:19196924

Affective neuroscience of pleasure: reward in humans and animals

PubMed Central

2010-01-01

Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness. PMID:18311558

Interaction of the Left Dorsolateral Prefrontal Cortex (l-DLPFC) and Right Orbitofrontal Cortex (OFC) in Hot and Cold Executive Functions: Evidence from Transcranial Direct Current Stimulation (tDCS).

PubMed

Nejati, Vahid; Salehinejad, Mohammad Ali; Nitsche, Michael A

2018-01-15

An organizing principle which has recently emerged proposes that executive functions (EF) can be divided into cognitive (cold) and affective/reward-related (hot) processes related to the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) respectively. A controversial question is whether cold and hot EF are functionally and structurally independent or not. This study investigated how the left DLPFC (l-DLPFC) and right OFC (r-OFC) interact in hot and cold EF using transcranial direct current stimulation (tDCS). Twenty-four healthy male subjects received anodal, cathodal and sham tDCS (20 min, 1.5 mA) over the l-DLPFC (F3) and r-OFC (Fp2) with a 72-h interval between each stimulation condition. After five minutes of stimulation, participants underwent a series of cold and hot EF tasks including the Go/No-Go and Tower of Hanoi (TOH) as measures of cold EF and the BART and temporal discounting tasks as measures of hot EF. Inhibitory control mostly benefited from anodal l-DLPFC/cathodal r-OFC tDCS. Planning and problem solving were more prominently affected by anodal l-DLPFC/cathodal r-OFC stimulation, although the reversed electrode position with the anode positioned over the r-OFC also affected some aspects of task performance. Risk-taking behavior and risky decision-making decreased under both anodal l-DLPFC/cathodal r-OFC and anodal r-OFC/cathodal l-DLPFC tDCS. Cold EF rely on DLPFC activation while hot EF rely on both, DLPFC and OFC activation. Results suggest that EF are placed on continuum with lateral and mesial prefrontal areas contributing to cold and hot aspects respectively. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Modulation of value representation by social context in the primate orbitofrontal cortex.

PubMed

Azzi, João C B; Sirigu, Angela; Duhamel, Jean-René

2012-02-07

Primates depend for their survival on their ability to understand their social environment, and their behavior is often shaped by social circumstances. We report that the orbitofrontal cortex, a brain region involved in motivation and reward, is tuned to social information. Macaque monkeys worked to collect rewards for themselves and two monkey partners. Behaviorally, monkeys discriminated between cues signaling large and small [corrected] rewards, and between cues signaling rewards to self only and reward to both self and another monkey, with a preference for the former over the latter in both instances. Single neurons recorded during this task encoded the meaning of visual cues that predicted the magnitude of future rewards, as well as the motivational value of rewards obtained in a social context. Furthermore, neuronal activity was found to track momentary social preferences and partner's identity and social rank. The orbitofrontal cortex thus contains key neuronal mechanisms for the evaluation of social information.

Regret and its avoidance: a neuroimaging study of choice behavior.

PubMed

Coricelli, Giorgio; Critchley, Hugo D; Joffily, Mateus; O'Doherty, John P; Sirigu, Angela; Dolan, Raymond J

2005-09-01

Human decisions can be shaped by predictions of emotions that ensue after choosing advantageously or disadvantageously. Indeed, anticipating regret is a powerful predictor of future choices. We measured brain activity using functional magnetic resonance imaging (fMRI) while subjects selected between two gambles wherein regret was induced by providing information about the outcome of the unchosen gamble. Increasing regret enhanced activity in the medial orbitofrontal region, the anterior cingulate cortex and the hippocampus. Notably, across the experiment, subjects became increasingly regret-aversive, a cumulative effect reflected in enhanced activity within medial orbitofrontal cortex and amygdala. This pattern of activity reoccurred just before making a choice, suggesting that the same neural circuitry mediates direct experience of regret and its anticipation. These results demonstrate that medial orbitofrontal cortex modulates the gain of adaptive emotions in a manner that may provide a substrate for the influence of high-level emotions on decision making.

Biased and unbiased perceptual decision-making on vocal emotions.

PubMed

Dricu, Mihai; Ceravolo, Leonardo; Grandjean, Didier; Frühholz, Sascha

2017-11-24

Perceptual decision-making on emotions involves gathering sensory information about the affective state of another person and forming a decision on the likelihood of a particular state. These perceptual decisions can be of varying complexity as determined by different contexts. We used functional magnetic resonance imaging and a region of interest approach to investigate the brain activation and functional connectivity behind two forms of perceptual decision-making. More complex unbiased decisions on affective voices recruited an extended bilateral network consisting of the posterior inferior frontal cortex, the orbitofrontal cortex, the amygdala, and voice-sensitive areas in the auditory cortex. Less complex biased decisions on affective voices distinctly recruited the right mid inferior frontal cortex, pointing to a functional distinction in this region following decisional requirements. Furthermore, task-induced neural connectivity revealed stronger connections between these frontal, auditory, and limbic regions during unbiased relative to biased decision-making on affective voices. Together, the data shows that different types of perceptual decision-making on auditory emotions have distinct patterns of activations and functional coupling that follow the decisional strategies and cognitive mechanisms involved during these perceptual decisions.

The human brain representation of odor identification.

PubMed

Kjelvik, Grete; Evensmoen, Hallvard R; Brezova, Veronika; Håberg, Asta K

2012-07-01

Odor identification (OI) tests are increasingly used clinically as biomarkers for Alzheimer's disease and schizophrenia. The aim of this study was to directly compare the neuronal correlates to identified odors vs. nonidentified odors. Seventeen females with normal olfactory function underwent a functional magnetic resonance imaging (fMRI) experiment with postscanning assessment of spontaneous uncued OI. An event-related analysis was performed to compare within-subject activity to spontaneously identified vs. nonidentified odors at the whole brain level, and in anatomic and functional regions of interest (ROIs) in the medial temporal lobe (MTL). Parameter estimate values and blood oxygenated level-dependent (BOLD) signal curves for correctly identified and nonidentified odors were derived from functional ROIs in hippocampus, entorhinal, piriform, and orbitofrontal cortices. Number of activated voxels and max parameter estimate values were obtained from anatomic ROIs in the hippocampus and the entorhinal cortex. At the whole brain level the correct OI gave rise to increased activity in the left entorhinal cortex and secondary olfactory structures, including the orbitofrontal cortex. Increased activation was also observed in fusiform, primary visual, and auditory cortices, inferior frontal plus inferior temporal gyri. The anatomic MTL ROI analysis showed increased activation in the left entorhinal cortex, right hippocampus, and posterior parahippocampal gyri in correct OI. In the entorhinal cortex and hippocampus the BOLD signal increased specifically in response to identified odors and decreased for nonidentified odors. In orbitofrontal and piriform cortices both identified and nonidentified odors gave rise to an increased BOLD signal, but the response to identified odors was significantly greater than that for nonidentified odors. These results support a specific role for entorhinal cortex and hippocampus in OI, whereas piriform and orbitofrontal cortices are active in both smelling and OI. Moreover, episodic as well as semantic memory systems appeared to support OI.

Social intelligence and adequate self-expression in patients with orbitofrontal cortex injury and in the criminals

PubMed Central

Pąchalska, Maria; Ledwoch, Beata; Moskała, Marek; Zieniewicz, Katarzyna; Mańko, Grzegorz; Polak, Jarosław

2012-01-01

Summary Background The aim of present article is to compare patients with damage to the orbitofrontal cortex and prison inmates in terms of social intelligence and social intelligence monitoring. In addition, personal principles and emotional regulation of behavior will be assessed in both groups. Material/Methods 20 patients with orbitofrontal cortical injury, 20 prisoners and 20 controls answered questions from the Social Interactions Assessment Questionnaire. Then they evaluated their self-disclosure, reported their emotions related to self-disclosure and declared their personal principles concerning conversations with strangers. Results The patients with damage to the orbitofrontal cortex disclosed themselves to a stranger less appropriately than did other subjects, and did not assess it critically. They also violated their own declared principles, but did not feel embarrassed because of that. The prison inmates spoke out less forthrightly on many topics and felt confused during the whole examination. Conclusions Damage to the the orbital part of frontal lobes may result in a disorder of self-disclosure monitoring and impairment of social intelligence in conversations with unknown persons. Prison inmates give information about themselves unwillingly, which may result from their specific experiences during criminal and judicatory procedures and confinement. PMID:22648252

Rule Encoding in Orbitofrontal Cortex and Striatum Guides Selection

PubMed Central

Castagno, Meghan D.; Hayden, Benjamin Y.

2016-01-01

Active maintenance of rules, like other executive functions, is often thought to be the domain of a discrete executive system. An alternative view is that rule maintenance is a broadly distributed function relying on widespread cortical and subcortical circuits. Tentative evidence supporting this view comes from research showing some rule selectivity in the orbitofrontal cortex and dorsal striatum. We recorded in these regions and in the ventral striatum, which has not been associated previously with rule representation, as macaques performed a Wisconsin Card Sorting Task. We found robust encoding of rule category (color vs shape) and rule identity (six possible rules) in all three regions. Rule identity modulated responses to potential choice targets, suggesting that rule information guides behavior by highlighting choice targets. The effects that we observed were not explained by differences in behavioral performance across rules and thus cannot be attributed to reward expectation. Our results suggest that rule maintenance and rule-guided selection of options are distributed processes and provide new insight into orbital and striatal contributions to executive control. SIGNIFICANCE STATEMENT Rule maintenance, an important executive function, is generally thought to rely on dorsolateral brain regions. In this study, we examined activity of single neurons in orbitofrontal cortex and in ventral and dorsal striatum of macaques in a Wisconsin Card Sorting Task. Neurons in all three areas encoded rules and rule categories robustly. Rule identity also affected neural responses to potential choice options, suggesting that stored information is used to influence decisions. These results endorse the hypothesis that rule maintenance is a broadly distributed mental operation. PMID:27807165

Distributed coding of actual and hypothetical outcomes in the orbital and dorsolateral prefrontal cortex

PubMed Central

Abe, Hiroshi; Lee, Daeyeol

2011-01-01

SUMMARY Knowledge about hypothetical outcomes from unchosen actions is beneficial only when such outcomes can be correctly attributed to specific actions. Here, we show that during a simulated rock-paper-scissors game, rhesus monkeys can adjust their choice behaviors according to both actual and hypothetical outcomes from their chosen and unchosen actions, respectively. In addition, neurons in both dorsolateral prefrontal cortex and orbitofrontal cortex encoded the signals related to actual and hypothetical outcomes immediately after they were revealed to the animal. Moreover, compared to the neurons in the orbitofrontal cortex, those in the dorsolateral prefrontal cortex were more likely to change their activity according to the hypothetical outcomes from specific actions. Conjunctive and parallel coding of multiple actions and their outcomes in the prefrontal cortex might enhance the efficiency of reinforcement learning and also contribute to their context-dependent memory. PMID:21609828

"Anything is good that stimulates thought" in the hippocampus. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Hofmann, Markus J.; Kuchinke, Lars

2015-06-01

While the emotional trias of brainstem, diencephalon, and orbitofrontal cortex is generally accepted to hold an affective function at its core, fewer researchers would agree that the least common denominator function of the hippocampus is affective [1]. There is a greater consensus on complementary learning systems theory proposing that in contrast to the outer cerebral cortex hosting more stable memories, synaptic associations in the hippocampus create novel knowledge in the context of episodic memories [2]. We chose Oscar Wilde's quote [3, p. 108] as title because we think that the novel hippocampal conjunction of for the most part familiar (long-term) knowledge patterns elicits the positive affect of appreciation [4,5].

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

PubMed

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

2017-05-01

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

Lateral orbitofrontal cortex anticipates choices and integrates prior with current information

PubMed Central

Nogueira, Ramon; Abolafia, Juan M.; Drugowitsch, Jan; Balaguer-Ballester, Emili; Sanchez-Vives, Maria V.; Moreno-Bote, Rubén

2017-01-01

Adaptive behavior requires integrating prior with current information to anticipate upcoming events. Brain structures related to this computation should bring relevant signals from the recent past into the present. Here we report that rats can integrate the most recent prior information with sensory information, thereby improving behavior on a perceptual decision-making task with outcome-dependent past trial history. We find that anticipatory signals in the orbitofrontal cortex about upcoming choice increase over time and are even present before stimulus onset. These neuronal signals also represent the stimulus and relevant second-order combinations of past state variables. The encoding of choice, stimulus and second-order past state variables resides, up to movement onset, in overlapping populations. The neuronal representation of choice before stimulus onset and its build-up once the stimulus is presented suggest that orbitofrontal cortex plays a role in transforming immediate prior and stimulus information into choices using a compact state-space representation. PMID:28337990

Face processing in different brain areas, and critical band masking.

PubMed

Rolls, Edmund T

2008-09-01

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size, view, and spatial frequency of faces and objects, and that these neurons show rapid processing and rapid learning. Critical band spatial frequency masking is shown to be a property of these face-selective neurons and of the human visual perception of faces. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximizing the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalization, and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses generalize to other views of the same face. A theory is described of how such invariant representations may be produced by self-organizing learning in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory utilizes either temporal or spatial continuity with an associative synaptic modification rule. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye-gaze, face view, and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the human orbitofrontal and pregenual cingulate cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

The representation of information about faces in the temporal and frontal lobes.

PubMed

Rolls, Edmund T

2007-01-07

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size and view of faces and objects, and that these neurons show rapid processing and rapid learning. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximising the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalisation and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses, generalise to other views of the same face. A theory is described of how such invariant representations may be produced in a hierarchically organised set of visual cortical areas with convergent connectivity. The theory proposes that neurons in these visual areas use a modified Hebb synaptic modification rule with a short-term memory trace to capture whatever can be captured at each stage that is invariant about objects as the objects change in retinal view, position, size and rotation. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye gaze, face view and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the orbitofrontal cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

Individual Variations in Maternal Care Early in Life Correlate with Later Life Decision-Making and c-Fos Expression in Prefrontal Subregions of Rats

PubMed Central

van Hasselt, Felisa N.; de Visser, Leonie; Tieskens, Jacintha M.; Cornelisse, Sandra; Baars, Annemarie M.; Lavrijsen, Marla; Krugers, Harm J.; van den Bos, Ruud; Joëls, Marian

2012-01-01

Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology–e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures. PMID:22693577

Orbitofrontal overactivation in reward processing in borderline personality disorder: the role of non-suicidal self-injury.

PubMed

Vega, Daniel; Ripollés, Pablo; Soto, Àngel; Torrubia, Rafael; Ribas, Joan; Monreal, Jose Antonio; Pascual, Juan Carlos; Salvador, Raymond; Pomarol-Clotet, Edith; Rodríguez-Fornells, Antoni; Marco-Pallarés, Josep

2018-02-01

Borderline Personality Disorder (BPD) is a disabling and difficult-to-treat mental disease. One of its core features is a significant difficulty in affect regulation, which is often accompanied by Non-Suicidal Self-Injury (NSSI). It is suggested that this type of behavior elicits positive emotions and mitigates emotional distress, and therefore can ultimately be reinforced and promoted. In spite of the high prevalence of NSSI behaviors (also in non-BPD samples), their role in modulating reward-related processes has not yet been investigated in BPD patients. In the present study, this lack of research was addressed. A large sample of BPD patients (N = 40), divided into two groups depending on the presence of NSSI, and a group of matched healthy controls underwent functional Magnetic Resonance Imaging (fMRI) while performing a gambling task. Patients who committed NSSI acts exhibited enhanced activation of the orbitofrontal cortex following an unexpected reward, when compared with controls and BPD patients with no NSSI behavior. In addition, the NSSI group showed diminished functional connectivity between the left orbitofrontal cortex and the right parahippocampal gyrus. These findings might suggest impaired ability to update reward associations of potential choices when both BPD and NSSI are present. We propose that the presence of NSSI involves alterations in the reward system independently of BPD, and thus can be considered as a possible phenotype for reward-related alterations.

Volumetric cerebral characteristics of children exposed to opiates and other substances in utero

PubMed Central

Walhovd, K. B.; Moe, V.; Slinning, K.; Due-Tønnessen, P.; Bjørnerud, A.; Dale, A. M.; van der Kouwe, A.; Quinn, B. T.; Kosofsky, B.; Greve, D.; Fischl, B.

2007-01-01

Morphometric cerebral characteristics were studied in children with prenatal poly-substance exposure (n =14) compared to controls (n = 14) without such exposure. Ten of the substance exposed children were born to mothers who used opiates (heroin) throughout the pregnancy. Groups were compared across 16 brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, lateral ventricles, inferior lateral ventricles, and the 3rd and 4th ventricles. In addition, continuous measurement of thickness across the entire cortical mantle was performed. Volumetric characteristics were correlated with ability and questionnaire assessments 2 years prior to scan. Compared to controls, the substance-exposed children had smaller intracranial and brain volumes, including smaller cerebral cortex, amygdala, accumbens area, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, and inferior lateral ventricles, and thinner cortex of the right anterior cingulate and lateral orbitofrontal cortex. Pallidum and putamen appeared especially reduced in the subgroup exposed to opiates. Only volumes of the right anterior cingulate, the right lateral orbitofrontal cortex and the accumbens area, showed some association with ability and questionnaire measures. The sample studied is rare, and hence small, so conclusions cannot be drawn with certainty. Morphometric group differences were observed, but associations with previous behavioral assessment were generally weak. Some of the volumetric differences, particularly thinner cortex in part of the right lateral orbitofrontal cortex, may be moderately involved in cognitive and behavioral difficulties more frequently experienced by opiate and poly-substance exposed children. PMID:17513131

Individual differences in the Behavioral Inhibition System are associated with orbitofrontal cortex and precuneus gray matter volume.

PubMed

Fuentes, Paola; Barrós-Loscertales, Alfonso; Bustamante, Juan Carlos; Rosell, Patricia; Costumero, Víctor; Ávila, César

2012-09-01

The Behavioral Inhibition System (BIS) is described in Gray's Reinforcement Sensitivity Theory as a hypothetical construct that mediates anxiety in animals and humans. The neuroanatomical correlates of this system are not fully clear, although they are known to involve the amygdala, the septohippocampal system, and the prefrontal cortex. Previous neuroimaging research has related individual differences in BIS with regional volume and functional variations in the prefrontal cortex, amygdala, and hippocampal formation. The aim of the present work was to study BIS-related individual differences and their relationship with brain regional volume. BIS sensitivity was assessed through the BIS/BAS questionnaire in a sample of male participants (N = 114), and the scores were correlated with brain regional volume in a voxel-based morphometry analysis. The results show a negative correlation between the BIS and the volume of the right and medial orbitofrontal cortices and the precuneus. Our results and previous findings suggest that individual differences in anxiety-related personality traits and their related psychopathology may be associated with reduced brain volume in certain structures relating to emotional control (i.e., the orbitofrontal cortex) and self-consciousness (i.e., the precuneus), as shown by our results.

Orbitofrontal volumes in early adolescence predict initiation of cannabis use: a 4-year longitudinal and prospective study.

PubMed

Cheetham, Ali; Allen, Nicholas B; Whittle, Sarah; Simmons, Julian G; Yücel, Murat; Lubman, Dan I

2012-04-15

There is growing evidence that long-term, heavy cannabis use is associated with alterations in regional brain volumes. Although these changes are frequently attributed to the neurotoxic effects of cannabis, it is possible that some abnormalities might predate use and represent markers of vulnerability. To date, no studies have examined whether structural brain abnormalities are present before the onset of cannabis use. This study aims to determine whether adolescents who have initiated cannabis use early (i.e., before age 17 years) show premorbid structural abnormalities in the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex. Participants (n = 121) were recruited from primary schools in Melbourne, Australia, as part of a larger study examining adolescent emotional development. Participants underwent structural magnetic resonance imaging at age 12 years and were assessed for cannabis use 4 years later, at age 16 years. At the follow-up assessment, 28 participants had commenced using cannabis (16 female subjects [57%]), and 93 had not (43 female subjects [46%]). Smaller orbitofrontal cortex volumes at age 12 years predicted initiation of cannabis use by age 16 years. The volumes of other regions (amygdala, hippocampus, and anterior cingulate cortex) did not predict later cannabis use. These findings suggest that structural abnormalities in the orbitofrontal cortex might contribute to risk for cannabis exposure. Although the results have important implications for understanding neurobiological predictors of cannabis use, further research is needed to understand their relationship with heavier patterns of use in adulthood as well as later abuse of other substances. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.

Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. The objective is to examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls. Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles).more » The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors. The results are: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls; (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use; and (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables. Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.« less

Orbitofrontal Function and Educational Attainment

ERIC Educational Resources Information Center

Spinella, Marcello; Miley, William M.

2004-01-01

Orbitofrontal cortex (OFC) plays important roles in processes of reward and self-regulation. Lesions of OFC induce changes in personality and social conduct characterized by behavioral disinhibition, impulsivity, reduced autonomy, lack of concern with negative consequences, and mood lability. Many of these processes relate to aspects of education,…

The Neural Correlates of Hierarchical Predictions for Perceptual Decisions.

PubMed

Weilnhammer, Veith A; Stuke, Heiner; Sterzer, Philipp; Schmack, Katharina

2018-05-23

Sensory information is inherently noisy, sparse, and ambiguous. In contrast, visual experience is usually clear, detailed, and stable. Bayesian theories of perception resolve this discrepancy by assuming that prior knowledge about the causes underlying sensory stimulation actively shapes perceptual decisions. The CNS is believed to entertain a generative model aligned to dynamic changes in the hierarchical states of our volatile sensory environment. Here, we used model-based fMRI to study the neural correlates of the dynamic updating of hierarchically structured predictions in male and female human observers. We devised a crossmodal associative learning task with covertly interspersed ambiguous trials in which participants engaged in hierarchical learning based on changing contingencies between auditory cues and visual targets. By inverting a Bayesian model of perceptual inference, we estimated individual hierarchical predictions, which significantly biased perceptual decisions under ambiguity. Although "high-level" predictions about the cue-target contingency correlated with activity in supramodal regions such as orbitofrontal cortex and hippocampus, dynamic "low-level" predictions about the conditional target probabilities were associated with activity in retinotopic visual cortex. Our results suggest that our CNS updates distinct representations of hierarchical predictions that continuously affect perceptual decisions in a dynamically changing environment. SIGNIFICANCE STATEMENT Bayesian theories posit that our brain entertains a generative model to provide hierarchical predictions regarding the causes of sensory information. Here, we use behavioral modeling and fMRI to study the neural underpinnings of such hierarchical predictions. We show that "high-level" predictions about the strength of dynamic cue-target contingencies during crossmodal associative learning correlate with activity in orbitofrontal cortex and the hippocampus, whereas "low-level" conditional target probabilities were reflected in retinotopic visual cortex. Our findings empirically corroborate theorizations on the role of hierarchical predictions in visual perception and contribute substantially to a longstanding debate on the link between sensory predictions and orbitofrontal or hippocampal activity. Our work fundamentally advances the mechanistic understanding of perceptual inference in the human brain. Copyright © 2018 the authors 0270-6474/18/385008-14$15.00/0.

Structural and functional connectivity of the subthalamic nucleus during vocal emotion decoding

PubMed Central

Frühholz, Sascha; Ceravolo, Leonardo; Grandjean, Didier

2016-01-01

Our understanding of the role played by the subthalamic nucleus (STN) in human emotion has recently advanced with STN deep brain stimulation, a neurosurgical treatment for Parkinson’s disease and obsessive-compulsive disorder. However, the potential presence of several confounds related to pathological models raises the question of how much they affect the relevance of observations regarding the physiological function of the STN itself. This underscores the crucial importance of obtaining evidence from healthy participants. In this study, we tested the structural and functional connectivity between the STN and other brain regions related to vocal emotion in a healthy population by combining diffusion tensor imaging and psychophysiological interaction analysis from a high-resolution functional magnetic resonance imaging study. As expected, we showed that the STN is functionally connected to the structures involved in emotional prosody decoding, notably the orbitofrontal cortex, inferior frontal gyrus, auditory cortex, pallidum and amygdala. These functional results were corroborated by probabilistic fiber tracking, which revealed that the left STN is structurally connected to the amygdala and the orbitofrontal cortex. These results confirm, in healthy participants, the role played by the STN in human emotion and its structural and functional connectivity with the brain network involved in vocal emotions. PMID:26400857

A biased activation theory of the cognitive and attentional modulation of emotion.

PubMed

Rolls, Edmund T

2013-01-01

Cognition can influence emotion by biasing neural activity in the first cortical region in which the reward value and subjective pleasantness of stimuli is made explicit in the representation, the orbitofrontal cortex (OFC). The same effect occurs in a second cortical tier for emotion, the anterior cingulate cortex (ACC). Similar effects are found for selective attention, to for example the pleasantness vs. the intensity of stimuli, which modulates representations of reward value and affect in the orbitofrontal and anterior cingulate cortices. The mechanisms for the effects of cognition and attention on emotion are top-down biased competition and top-down biased activation. Affective and mood states can in turn influence memory and perception, by backprojected biasing influences. Emotion-related decision systems operate to choose between gene-specified rewards such as taste, touch, and beauty. Reasoning processes capable of planning ahead with multiple steps held in working memory in the explicit system can allow the gene-specified rewards not to be selected, or to be deferred. The stochastic, noisy, dynamics of decision-making systems in the brain may influence whether decisions are made by the selfish-gene-specified reward emotion system, or by the cognitive reasoning system that explicitly calculates reward values that are in the interests of the individual, the phenotype.

Reduced Orbitofrontal and Temporal Grey Matter in a Community Sample of Maltreated Children

ERIC Educational Resources Information Center

De Brito, Stephane A.; Viding, Essi; Sebastian, Catherine L.; Kelly, Philip A.; Mechelli, Andrea; Maris, Helen; McCrory, Eamon J.

2013-01-01

Background: Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to…

Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers.

PubMed

London, Edythe D; Simon, Sara L; Berman, Steven M; Mandelkern, Mark A; Lichtman, Aaron M; Bramen, Jennifer; Shinn, Ann K; Miotto, Karen; Learn, Jennifer; Dong, Yun; Matochik, John A; Kurian, Varughese; Newton, Thomas; Woods, Roger; Rawson, Richard; Ling, Walter

2004-01-01

Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood. To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers. Two groups were compared by measures of mood and cerebral glucose metabolism ([18F]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task. Participants were recruited from the general community to a research center. Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women). Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum. Abusers of MA provided higher self-ratings of depression and anxiety than control subjects and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitofrontal cortex and positively with amygdala activity. Abusers of MA have abnormalities in brain regions implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence.

Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

PubMed

Zois, E; Vollstädt-Klein, S; Hoffmann, S; Reinhard, I; Charlet, K; Beck, A; Jorde, A; Kirsch, M; Walter, H; Heinz, A; Kiefer, F

2017-10-01

Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dissociable contributions of the human amygdala and orbitofrontal cortex to incentive motivation and goal selection.

PubMed

Arana, F Sergio; Parkinson, John A; Hinton, Elanor; Holland, Anthony J; Owen, Adrian M; Roberts, Angela C

2003-10-22

Theories of incentive motivation attempt to capture the way in which objects and events in the world can acquire high motivational value and drive behavior, even in the absence of a clear biological need. In addition, for an individual to select the most appropriate goal, the incentive values of competing desirable objects need to be defined and compared. The present study examined the neural substrates by which appetitive incentive value influences prospective goal selection, using positron emission tomographic neuroimaging in humans. Sated subjects were shown a series of restaurant menus that varied in incentive value, specifically tailored for each individual, and in half the trials, were asked to make a selection from the menu. The amygdala was activated by high-incentive menus regardless of whether a choice was required. Indeed, activity in this region varied as a function of individual subjective ratings of incentive value. In contrast, distinct regions of the orbitofrontal cortex were recruited both during incentive judgments and goal selection. Activity in the medial orbital cortex showed a greater response to high-incentive menus and when making a choice, with the latter activity also correlating with subjective ratings of difficulty. Lateral orbitofrontal activity was observed selectively when participants had to suppress responses to alternative desirable items to select their most preferred. Taken together, these data highlight the differential contribution of the amygdala and regions within the orbitofrontal cortex in a neural system underlying the selection of goals based on the prospective incentive value of stimuli, over and above homeostatic influences.

Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep.

PubMed

Onisawa, Naomi; Manabe, Hiroyuki; Mori, Kensaku

2017-01-01

During slow-wave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-to-down transition. Such temporal coordination between neocortical up- and downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition. Simultaneous recordings of local field potentials and spike activities in the anterior piriform cortex (APC) and orbitofrontal cortex (OFC) during slow-wave sleep showed that APC sharp waves tended to occur during two distinct phases of OFC upstate: early phase, shortly after the down-to-up transition, and late phase, shortly before the up-to-down transition, suggesting that during slow-wave sleep, olfactory cortex and OFC areas communicate preferentially in the specific time windows. Copyright © 2017 the American Physiological Society.

Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep

PubMed Central

Onisawa, Naomi; Mori, Kensaku

2016-01-01

During slow-wave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-to-down transition. Such temporal coordination between neocortical up- and downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition. NEW & NOTEWORTHY Simultaneous recordings of local field potentials and spike activities in the anterior piriform cortex (APC) and orbitofrontal cortex (OFC) during slow-wave sleep showed that APC sharp waves tended to occur during two distinct phases of OFC upstate: early phase, shortly after the down-to-up transition, and late phase, shortly before the up-to-down transition, suggesting that during slow-wave sleep, olfactory cortex and OFC areas communicate preferentially in the specific time windows. PMID:27733591

Remembering beauty: roles of orbitofrontal and hippocampal regions in successful memory encoding of attractive faces.

PubMed

Tsukiura, Takashi; Cabeza, Roberto

2011-01-01

Behavioral data have shown that attractive faces are better remembered but the neural mechanisms of this effect are largely unknown. To investigate this issue, female participants were scanned with event-related functional MRI (fMRI) while rating the attractiveness of male faces. Memory for the faces was tested after fMRI scanning and was used to identify successful encoding activity (subsequent memory paradigm). As expected, attractive faces were remembered better than other faces. The study yielded three main fMRI findings. First, activity in the right orbitofrontal cortex increased linearly as a function of attractiveness ratings. Second, activity in the left hippocampus increased as a function of subsequent memory (subsequent misses

Remembering beauty: Roles of orbitofrontal and hippocampal regions in successful memory encoding of attractive faces

PubMed Central

Tsukiura, Takashi; Cabeza, Roberto

2010-01-01

Behavioral data have shown that attractive faces are better remembered but the neural mechanisms of this effect are largely unknown. To investigate this issue, female participants were scanned with event-related functional MRI (fMRI) while rating the attractiveness of male faces. Memory for the faces was tested after fMRI scanning and was used to identify successful encoding activity (subsequent memory paradigm). As expected, attractive faces were remembered better than other faces. The study yielded three main fMRI findings. First, activity in the right orbitofrontal cortex increased linearly as a function of attractiveness ratings. Second, activity in the left hippocampus increased as a function of subsequent memory (subsequent misses

Orchestrating emotion and action in an evolutionary framework. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Arbib, Michael A.

2015-06-01

The lead author of the Quartet Theory [10] is, appropriately enough, an expert on the neuroscience linking music and emotion, and examples of this linkage are a welcome feature of the article. Actually, the article charts two quartets: A structural quartet of affect systems centered on (i) brainstem, (ii) diencephalon, (iii) hippocampus and (iv) orbitofrontal cortex.

Neurocircuitry of Addiction

PubMed Central

Koob, George F; Volkow, Nora D

2010-01-01

Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: ‘binge/intoxication', ‘withdrawal/negative affect', and ‘preoccupation/anticipation' (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex–dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction. PMID:19710631

A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy

PubMed Central

Sidhu, Meneka K.; Stretton, Jason; Winston, Gavin P.; Bonelli, Silvia; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Koepp, Matthias J.

2013-01-01

Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment. PMID:23674488

Distinct frontal regions subserve evaluation of linguistic and emotional aspects of speech intonation.

PubMed

Wildgruber, D; Hertrich, I; Riecker, A; Erb, M; Anders, S; Grodd, W; Ackermann, H

2004-12-01

In addition to the propositional content of verbal utterances, significant linguistic and emotional information is conveyed by the tone of speech. To differentiate brain regions subserving processing of linguistic and affective aspects of intonation, discrimination of sentences differing in linguistic accentuation and emotional expressiveness was evaluated by functional magnetic resonance imaging. Both tasks yielded rightward lateralization of hemodynamic responses at the level of the dorsolateral frontal cortex as well as bilateral thalamic and temporal activation. Processing of linguistic and affective intonation, thus, seems to be supported by overlapping neural networks comprising partially right-sided brain regions. Comparison of hemodynamic activation during the two different tasks, however, revealed bilateral orbito-frontal responses restricted to the affective condition as opposed to activation of the left lateral inferior frontal gyrus confined to evaluation of linguistic intonation. These findings indicate that distinct frontal regions contribute to higher level processing of intonational information depending on its communicational function. In line with other components of language processing, discrimination of linguistic accentuation seems to be lateralized to the left inferior-lateral frontal region whereas bilateral orbito-frontal areas subserve evaluation of emotional expressiveness.

Neural mechanisms of reinforcement learning in unmedicated patients with major depressive disorder.

PubMed

Rothkirch, Marcus; Tonn, Jonas; Köhler, Stephan; Sterzer, Philipp

2017-04-01

According to current concepts, major depressive disorder is strongly related to dysfunctional neural processing of motivational information, entailing impairments in reinforcement learning. While computational modelling can reveal the precise nature of neural learning signals, it has not been used to study learning-related neural dysfunctions in unmedicated patients with major depressive disorder so far. We thus aimed at comparing the neural coding of reward and punishment prediction errors, representing indicators of neural learning-related processes, between unmedicated patients with major depressive disorder and healthy participants. To this end, a group of unmedicated patients with major depressive disorder (n = 28) and a group of age- and sex-matched healthy control participants (n = 30) completed an instrumental learning task involving monetary gains and losses during functional magnetic resonance imaging. The two groups did not differ in their learning performance. Patients and control participants showed the same level of prediction error-related activity in the ventral striatum and the anterior insula. In contrast, neural coding of reward prediction errors in the medial orbitofrontal cortex was reduced in patients. Moreover, neural reward prediction error signals in the medial orbitofrontal cortex and ventral striatum showed negative correlations with anhedonia severity. Using a standard instrumental learning paradigm we found no evidence for an overall impairment of reinforcement learning in medication-free patients with major depressive disorder. Importantly, however, the attenuated neural coding of reward in the medial orbitofrontal cortex and the relation between anhedonia and reduced reward prediction error-signalling in the medial orbitofrontal cortex and ventral striatum likely reflect an impairment in experiencing pleasure from rewarding events as a key mechanism of anhedonia in major depressive disorder. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cortical thickness, cortico-amygdalar networks, and externalizing behaviors in healthy children.

PubMed

Ameis, Stephanie H; Ducharme, Simon; Albaugh, Matthew D; Hudziak, James J; Botteron, Kelly N; Lepage, Claude; Zhao, Lu; Khundrakpam, Budhachandra; Collins, D Louis; Lerch, Jason P; Wheeler, Anne; Schachar, Russell; Evans, Alan C; Karama, Sherif

2014-01-01

Fronto-amygdalar networks are implicated in childhood psychiatric disorders characterized by high rates of externalizing (aggressive, noncompliant, oppositional) behavior. Although externalizing behaviors are distributed continuously across clinical and nonclinical samples, little is known about how brain variations may confer risk for problematic behavior. Here, we studied cortical thickness, amygdala volume, and cortico-amygdalar network correlates of externalizing behavior in a large sample of healthy children. Two hundred ninety-seven healthy children (6-18 years; mean = 12 ± 3 years), with 517 magnetic resonance imaging scans, from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development, were studied. Relationships between externalizing behaviors (measured with the Child Behavior Checklist) and cortical thickness, amygdala volume, and cortico-amygdalar structural networks were examined using first-order linear mixed-effects models, after controlling for age, sex, scanner, and total brain volume. Results significant at p ≤ .05, following multiple comparison correction, are reported. Left orbitofrontal, right retrosplenial cingulate, and medial temporal cortex thickness were negatively correlated with externalizing behaviors. Although amygdala volume alone was not correlated with externalizing behaviors, an orbitofrontal cortex-amygdala network predicted rates of externalizing behavior. Children with lower levels of externalizing behaviors exhibited positive correlations between orbitofrontal cortex and amygdala structure, while these regions were not correlated in children with higher levels of externalizing behavior. Our findings identify key cortical nodes in frontal, cingulate, and temporal cortex associated with externalizing behaviors in children; and indicate that orbitofrontal-amygdala network properties may influence externalizing behaviors, along a continuum and across healthy and clinical samples. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Lateral Orbitofrontal Inactivation Dissociates Devaluation-Sensitive Behavior and Economic Choice.

PubMed

Gardner, Matthew P H; Conroy, Jessica S; Shaham, Michael H; Styer, Clay V; Schoenbaum, Geoffrey

2017-12-06

How do we choose between goods that have different subjective values, like apples and oranges? Neuroeconomics proposes that this is done by reducing complex goods to a single unitary value to allow comparison. This value is computed "on the fly" from the underlying model of the goods space, allowing decisions to meet current needs. This is termed "model-based" behavior to distinguish it from pre-determined, habitual, or "model-free" behavior. The lateral orbitofrontal cortex (OFC) supports model-based behavior in rats and primates, but whether the OFC is necessary for economic choice is less clear. Here we tested this question by optogenetically inactivating the lateral OFC in rats in a classic model-based task and during economic choice. Contrary to predictions, inactivation disrupted model-based behavior without affecting economic choice. Published by Elsevier Inc.

Thinking Outside the Box: Orbitofrontal Cortex, Imagination, and How We Can Treat Addiction.

PubMed

Schoenbaum, Geoffrey; Chang, Chun-Yun; Lucantonio, Federica; Takahashi, Yuji K

2016-12-01

Addiction involves an inability to control drug-seeking behavior. While this may be thought of as secondary to an overwhelming desire for drugs, it could equally well reflect a failure of the brain mechanisms that allow addicts to learn about and mentally simulate non-drug consequences. Importantly, this process of mental simulation draws upon, but is not normally bound by, our past experiences. Rather we have the ability to think outside the box of our past, integrating knowledge gained from a variety of similar and not-so-similar life experiences to derive estimates or imagine what might happen next. These estimates influence our current behavior directly and also affect future behavior by serving as the background against which outcomes are evaluated to support learning. Here we will review evidence, from our own work using a Pavlovian over-expectation task as well as from other sources, that the orbitofrontal cortex is a critical node in the neural circuit that generates these estimates. Further we will offer the specific hypothesis that degradation of this function secondary to drug-induced changes is a critical and likely addressable part of addiction.

Cerebral interactions of pain and reward and their relevance for chronic pain.

PubMed

Becker, Susanne; Gandhi, Wiebke; Schweinhardt, Petra

2012-06-29

Pain and reward are opponent, interacting processes. Such interactions are enabled by neuroanatomical and neurochemical overlaps of brain systems that process pain and reward. Cerebral processing of hedonic ('liking') and motivational ('wanting') aspects of reward can be separated: the orbitofrontal cortex and opioids play an important role for the hedonic experience, and the ventral striatum and dopamine predominantly process motivation for reward. Supported by neuroimaging studies, we present here the hypothesis that the orbitofrontal cortex and opioids are responsible for pain modulation by hedonic experience, while the ventral striatum and dopamine mediate motivational effects on pain. A rewarding stimulus that appears to be particularly important in the context of pain is pain relief. Further, reward, including pain relief, leads to operant learning, which can affect pain sensitivity. Indirect evidence points at brain mechanisms that might underlie pain relief as a reward and related operant learning but studies are scarce. Investigating the cerebral systems underlying pain-reward interactions as well as related operant learning holds the potential of better understanding mechanisms that contribute to the development and maintenance of chronic pain, as detailed in the last section of this review. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Midbrain response to milkshake correlates with ad libitum milkshake intake in the absence of hunger.

PubMed

Nolan-Poupart, Sarah; Veldhuizen, Maria G; Geha, Paul; Small, Dana M

2013-01-01

There is now widespread agreement that individual variation in the neural circuits representing the reinforcing properties of foods may be associated with risk for overeating and obesity. What is currently unknown is how and whether brain response to a food is related to immediate subsequent intake of that food. Here we used functional magnetic resonance imaging (fMRI) to test whether response to a palatable milkshake is associated with subsequent ad libitum milkshake consumption. We predicted that enhanced responses in key reward regions (insula, striatum, midbrain, medial orbitofrontal cortex) and decreased responses in regions implicated in self-control (lateral prefrontal and lateral orbitofrontal cortex) would be associated with greater intake. We found a significant positive association between response to milkshake in the periaqueductal gray region of the midbrain and ad libitum milkshake intake. Although strong bilateral insular responses were observed during consumption of the milkshake this response did not correlate with subsequent intake. The associations observed in the midbrain and orbitofrontal cortex were uninfluenced by ratings of hunger, which were near neutral. We conclude that midbrain response to a palatable food is related to eating in the absence of hunger. Copyright © 2012 Elsevier Ltd. All rights reserved.

Volumetric abnormalities in connectivity-based subregions of the thalamus in patients with chronic schizophrenia.

PubMed

Kim, Jae-Jin; Kim, Dae-Jin; Kim, Tae-Gyun; Seok, Jeong-Ho; Chun, Ji Won; Oh, Maeng-Keun; Park, Hae-Jeong

2007-12-01

The thalamus, which consists of multiple subnuclei, has been of particular interest in the study of schizophrenia. This study aimed to identify abnormalities in the connectivity-based subregions of the thalamus in patients with schizophrenia. Thalamic volume was measured by a manual tracing on superimposed images of T1-weighted and diffusion tensor images in 30 patients with schizophrenia and 22 normal volunteers. Cortical regional volumes automatically measured by a surface-based approach and thalamic subregional volumes measured by a connectivity-based technique were compared between the two groups and their correlations between the connected regions were calculated in each group. Volume reduction was observed in the bilateral orbitofrontal cortices and the left cingulate gyrus on the cortical side, whereas in subregions connected to the right orbitofrontal cortex and bilateral parietal cortices on the thalamic side. Significant volumetric correlations were identified between the right dorsal prefrontal cortex and its related thalamic subregion and between the left parietal cortex and its related thalamic subregion only in the normal group. Our results suggest that patients with schizophrenia have a structural deficit in the corticothalamic systems, especially in the orbitofrontal-thalamic system. Our findings may present evidence of corticothalamic connection problems in schizophrenia.

Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder.

PubMed

Schweren, L J S; Hartman, C A; Zwiers, M P; Heslenfeld, D J; Franke, B; Oosterlaan, J; Buitelaar, J K; Hoekstra, P J

2016-04-01

Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity within the frontal-striatal and mesolimbic pathways, in a large sample of children, adolescents and young adults with ADHD. Participants with ADHD (N=172; mean age 17, range 9-26) underwent diffusion-weighted MRI scanning, along with an age- and gendermatched group of 96 control participants. Five study-specific white matter tract masks (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medialprefrontal-striatal) were created. First we analyzed case-control differences in fractional anisotropy (FA) and mean diffusivity (MD) within each tract. Second, FA and MD in each tract was predicted from cumulative stimulant intake within the ADHD group. After correction for multiple testing, participants with ADHD showed reduced FA in the orbitofrontal-striatal pathway (p=0.010, effect size=0.269). Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway (p=0.011, effect size=-0.164), but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. It fell short of significance after adding ADHD severity or ADHD type to the model (p=0.036 and p=0.094, respectively), while the effect size changed little. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD. Longitudinal studies including a drug-naïve baseline assessment are needed to distinguish between-subject variability in ADHD severity from treatment effects. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

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

PubMed

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

2011-01-01

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

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.

The neurobiology of psychopathy: a neurodevelopmental perspective.

PubMed

Gao, Yu; Glenn, Andrea L; Schug, Robert A; Yang, Yaling; Raine, Adrian

2009-12-01

We provide an overview of the neurobiological underpinnings of psychopathy. Cognitive and affective-emotional processing deficits are associated with abnormal brain structure and function, particularly the amygdala and orbitofrontal cortex. There is limited evidence of lower cortisol levels being associated with psychopathic personality. Initial developmental research is beginning to suggest that these neurobiological processes may have their origins early in life. Findings suggest that psychopathic personality may, in part, have a neurodevelopmental basis. Future longitudinal studies delineating neurobiological correlates of the analogues of interpersonal-affective and antisocial features of psychopathy in children are needed to further substantiate a neurodevelopmental hypothesis of psychopathy.

Choice Behavior Guided by Learned, But Not Innate, Taste Aversion Recruits the Orbitofrontal Cortex.

PubMed

Ramírez-Lugo, Leticia; Peñas-Rincón, Ana; Ángeles-Durán, Sandybel; Sotres-Bayon, Francisco

2016-10-12

The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats. Interestingly, we found that inactivation of the orbitofrontal cortex (OFC), but not the dorsal or ventral medial prefrontal cortices, blocked retrieval of choice CTA. However, OFC inactivation left retrieval of no-choice CTA intact, suggesting its role in guiding choice, but not in retrieval of CTA memory. Consistently, OFC activity increased in the choice condition compared with no-choice, as measured with c-Fos immunolabeling. Notably, OFC inactivation did not affect choice behavior when it was guided by innate taste aversion. Consistent with an anterior insular cortex (AIC) involvement in storing taste memories, we found that AIC inactivation impaired retrieval of both choice and no-choice CTA. Therefore, this study provides evidence for OFC's role in guiding choice behavior and shows that this is dissociable from AIC-dependent taste aversion memory. Together, our results suggest that OFC is required and recruited to guide choice selection between options of taste associations relayed from AIC. Survival and mental health depend on being able to choose stimuli not associated with danger. This is particularly important when danger is associated with stimuli that we ingest. Although much is known about the brain mechanisms that underlie associations with dangerous taste stimuli, very little is known about how these stored emotional associations guide behavior when it involves choice. By combining pharmacological and immunohistochemistry tools with taste-guided tasks, our study provides evidence for the key role of orbitofrontal cortex activity in choice behavior and shows that this is dissociable from the adjacent insular cortex-dependent taste aversion memory. Understanding the brain mechanisms that underlie the impact that emotional associations have on survival choice behaviors may lead to better treatments for mental disorders characterized by emotional decision-making deficits. Copyright © 2016 the authors 0270-6474/16/3610574-10$15.00/0.

Neuroscience of affect: Brain mechanisms of pleasure and displeasure

PubMed Central

Berridge, Kent C.; Kringelbach, Morten L.

2013-01-01

Affective neuroscience aims to understand how affect (pleasure or displeasure) is created by brains. Progress is aided by recognizing that affect has both objective and subjective features. Those dual aspects reflect that affective reactions are generated by neural mechanisms, selected in evolution based on their real (objective) consequences for genetic fitness. We review evidence for neural representation of pleasure in the brain (gained largely from neuroimaging studies), and evidence for the causal generation of pleasure (gained largely from brain manipulation studies). We suggest that representation and causation may actually reflect somewhat separable neuropsychological functions. Representation reaches an apex in limbic regions of prefrontal cortex, especially orbitofrontal cortex, influencing decisions and affective regulation. Causation of core pleasure or liking reactions is much more subcortically weighted, and sometimes surprisingly localized. Pleasure liking is especially generated by restricted hedonic hotspot circuits in nucleus accumbens and ventral pallidum. Another example of localized valence generation, beyond hedonic hotspots, is an affective keyboard mechanism in nucleus accumbens for releasing intense motivations such as either positively-valenced desire and/or negatively-valenced dread. PMID:23375169

Effects of self-administered cocaine in adolescent and adult male rats on orbitofrontal cortex-related neurocognitive functioning

PubMed Central

Harvey, Roxann C.; Dembro, Kimberly A.; Rajagopalan, Kiran; Mutebi, Michael M.; Kantak, Kathleen M.

2010-01-01

Rationale Deficits in amygdala-related stimulus-reward learning are produced following 18 drug-free days of cocaine self-administration or its passive delivery in rats exposed during adulthood. No deficits in stimulus-reward learning are produced by cocaine exposure initiated during adolescence. Objectives To determine if age of initiating cocaine exposure differentially affects behavioral functioning of an additional memory system linked to cocaine addiction, the orbitofrontal cortex. Materials and methods A yoked-triad design (n=8) was used. One rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling drug delivery (1.0 mg/kg) self-administered cocaine from either P37–P59 or P77–P99, and then underwent 18 drug-free days (P60–P77 vs. P100–P117). Rats next were tested for acquisition of odor-delayed win-shift behavior conducted over 15 sessions (P78–P96 vs. P118–P136). Results Cocaine self-administration did not differ between adults and adolescents. During the test phase of the odor-delayed win-shift task (relatively difficult task demands), rats from both drug-onset ages showed learning deficits. Rats with cocaine self-administration experience committed more errors and had longer session latencies compared to rats passively receiving saline or cocaine. Rats with adolescent-onset cocaine self-administration experience showed an additional learning deficit by requiring more sessions to reach criterion levels for task acquisition compared to same-aged passive saline controls or rats with adult-onset cocaine self-administration experience. Rats passively receiving cocaine did not differ from the passive saline control from either age group. Conclusions Rats with adolescent-onset cocaine self-administration experience were more impaired in an orbitofrontal cortex-related learning task than rats with adult-onset cocaine self-administration experience. PMID:19513699

Increased Cortical Thickness in Male-to-Female Transsexualism.

PubMed

Luders, Eileen; Sánchez, Francisco J; Tosun, Duygu; Shattuck, David W; Gaser, Christian; Vilain, Eric; Toga, Arthur W

2012-08-01

The degree to which one identifies as male or female has a profound impact on one's life. Yet, there is a limited understanding of what contributes to this important characteristic termed gender identity . In order to reveal factors influencing gender identity, studies have focused on people who report strong feelings of being the opposite sex, such as male-to-female (MTF) transsexuals. To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males. Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus). These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men.

Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula

PubMed Central

Castro, Daniel C.; Berridge, Kent C.

2017-01-01

Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as “liking” for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the form of an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots. Opioid/orexin stimulations in either cortical hotspot activated Fos throughout a distributed “hedonic circuit” involving cortical and subcortical structures. Conversely, cortical coldspot stimulation activated circuitry for “hedonic suppression.” Finally, food intake was increased by stimulations at several prefrontal cortical sites, indicating that the anatomical substrates in cortex for enhancing the motivation to eat are discriminable from those for hedonic impact. PMID:29073109

Oxytocin enhances brain function in children with autism.

PubMed

Gordon, Ilanit; Vander Wyk, Brent C; Bennett, Randi H; Cordeaux, Cara; Lucas, Molly V; Eilbott, Jeffrey A; Zagoory-Sharon, Orna; Leckman, James F; Feldman, Ruth; Pelphrey, Kevin A

2013-12-24

Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.

Unpacking the neural associations of emotion and judgment in emotion-congruent judgment

PubMed Central

Beer, Jennifer S.

2012-01-01

The current study takes a new approach to understand the neural systems that support emotion-congruent judgment. The bulk of previous neural research has inferred emotional influences on judgment from disadvantageous judgments or non-random individual differences. The current study manipulated the influence of emotional information on judgments of stimuli that were equivocally composed of positive and negative attributes. Emotion-congruent processing was operationalized in two ways: neural activation significantly associated with primes that lead to emotionally congruent judgments and neural activation significantly associated with judgments that were preceded by emotionally congruent primes. Distinct regions of medial orbitofrontal cortex were associated with these patterns of emotion-congruent processing. Judgments that were incongruent with preceding primes were associated with dorsomedial prefrontal cortex, ventrolateral prefrontal cortex and lateral orbitofrontal cortex activity. The current study demonstrates a new approach to investigate the neural systems associated with emotion-congruent judgment. The findings suggest that medial OFC may support attentional processes that underlie emotion-congruent judgment. PMID:21511825

[Orbitofrontal cortex and morality].

PubMed

Funayama, Michitaka; Mimura, Masaru

2012-10-01

Research on the neural substrates of morality is a recently emerging field in neuroscience. The anatomical structures implicated to play a role in morality include the frontal lobe, temporal lobe, cingulate gyrus, amygdala, hippocampus, and basal ganglia. In particular, the orbitofrontal or ventromedial prefrontal areas are thought to be involved in decision-making, and damage to these areas is likely to cause decision-making deficits and/or problems in impulsive control, which may lead to antisocial and less moral behaviors. In this article, we focus on case presentation and theory development with regard to moral judgment. First, we discuss notable cases and syndromes developing after orbitofrontal/ventromedial prefrontal damage, such as the famous cases of Gage and EVR, cases of childhood orbitofrontal damage, forced collectionism, squalor syndrome, and hypermoral syndrome. We then review the proposed theories and neuropsychological mechanisms underlying decision-making deficits following orbitofrontal/ventromedial prefrontal damage, including the somatic-marker hypothesis, reversal learning, preference judgment, theory of mind, and moral dilemma.

Anatomy of a Decision: Striato-Orbitofrontal Interactions in Reinforcement Learning, Decision Making, and Reversal

ERIC Educational Resources Information Center

Frank, Michael J.; Claus, Eric D.

2006-01-01

The authors explore the division of labor between the basal ganglia-dopamine (BG-DA) system and the orbitofrontal cortex (OFC) in decision making. They show that a primitive neural network model of the BG-DA system slowly learns to make decisions on the basis of the relative probability of rewards but is not as sensitive to (a) recency or (b) the…

Orbitofrontal and hippocampal contributions to memory for face-name associations: the rewarding power of a smile.

PubMed

Tsukiura, Takashi; Cabeza, Roberto

2008-01-01

Memory processes can be enhanced by reward, and social signals such a smiling face can be rewarding to humans. Using event-related functional MRI (fMRI), we investigated the rewarding effect of a simple smile during the encoding and retrieval of face-name associations. During encoding, participants viewed smiling or neutral faces, each paired with a name, and during retrieval, only names were presented, and participants retrieved the associated facial expressions. Successful memory activity of face-name associations was identified by comparing remembered vs. forgotten trials during both encoding and retrieval, and the effect of a smile was identified by comparing successful memory trials for smiling vs. neutral faces. The study yielded three main findings. First, behavioral results showed that the retrieval of face-name associations was more accurate and faster for smiling than neutral faces. Second, the orbitofrontal cortex and the hippocampus showed successful encoding and retrieval activations, which were greater for smiling than neutral faces. Third, functional connectivity between the orbitofrontal cortex and the hippocampus during successful encoding and retrieval was stronger for smiling than neutral faces. As a part of the reward system, the orbitofrontal cortex may modulate memory processes of face-name associations mediated by the hippocampus. Interestingly, the effect of a smile during retrieval was found even though only names were presented as retrieval cues, suggesting that the effect was mediated by face imagery. Taken together, the results demonstrate how rewarding social signals from a smiling face can enhance relational memory for face-name associations.

[Affective and cognitive decision making in major depression: influence of the prefrontal cortex, serotonin transporter genotype and personality traits].

PubMed

Must, Anita; Horváth, Szatmár; Janka, Zoltán

2008-05-30

Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and suboptimal decision-making strategies, which are mediated by several brain regions. In the development of these symptoms the pathology of the prefrontal cortex (PFC), including the dorsolateral, ventromedial and orbitofrontal regions, may also play an important role. Neuropsychological assessment is a useful tool in detecting and measuring these deficiencies, showing that patients with MDD exhibit altered sensitivity to reward and punishment. However, impairment of emotional decision-making strategies in MDD is influenced by genetic variations (5-HTTLPR polymorphism) and personality traits, which seem to have a higher predictive value on decision making performance than the clinical symptoms.

The development of the ventral prefrontal cortex and social flexibility.

PubMed

Nelson, Eric E; Guyer, Amanda E

2011-07-01

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

Double dissociation of value computations in orbitofrontal and anterior cingulate neurons

PubMed Central

Kennerley, Steven W.; Behrens, Timothy E. J.; Wallis, Jonathan D.

2011-01-01

Damage to prefrontal cortex (PFC) impairs decision-making, but the underlying value computations that might cause such impairments remain unclear. Here we report that value computations are doubly dissociable within PFC neurons. While many PFC neurons encoded chosen value, they used opponent encoding schemes such that averaging the neuronal population eliminated value coding. However, a special population of neurons in anterior cingulate cortex (ACC) - but not orbitofrontal cortex (OFC) - multiplex chosen value across decision parameters using a unified encoding scheme, and encoded reward prediction errors. In contrast, neurons in OFC - but not ACC - encoded chosen value relative to the recent history of choice values. Together, these results suggest complementary valuation processes across PFC areas: OFC neurons dynamically evaluate current choices relative to recent choice values, while ACC neurons encode choice predictions and prediction errors using a common valuation currency reflecting the integration of multiple decision parameters. PMID:22037498

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

PubMed

Volkow, N D; Gillespie, H; Mullani, N; Tancredi, L; Grant, C; Valentine, A; Hollister, L

1996-05-31

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

The Development of the Ventral Prefrontal Cortex and Social Flexibility

PubMed Central

Nelson, Eric E.; Guyer, Amanda E.

2011-01-01

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

Musical Creativity “Revealed” in Brain Structure: Interplay between Motor, Default Mode, and Limbic Networks

PubMed Central

Bashwiner, David M.; Wertz, Christopher J.; Flores, Ranee A.; Jung, Rex E.

2016-01-01

Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain-general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas, and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus, and temporal pole), and c) emotion-related regions (orbitofrontal cortex, temporal pole, and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music. PMID:26888383

Changes in cue-induced, prefrontal cortex activity with video-game play.

PubMed

Han, Doug Hyun; Kim, Yang Soo; Lee, Yong Sik; Min, Kyung Joon; Renshaw, Perry F

2010-12-01

Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.

Regional homogeneity associated with overgeneral autobiographical memory of first-episode treatment-naive patients with major depressive disorder in the orbitofrontal cortex: A resting-state fMRI study.

PubMed

Liu, Yansong; Zhao, Xudong; Cheng, Zaohuo; Zhang, Fuquan; Chang, Jun; Wang, Haosen; Xie, Rukui; Wang, Zhiqiang; Cao, Leiming; Wang, Guoqiang

2017-02-01

Overgeneral autobiographical memory (OGM) is involved in the onset and maintenance of depression. Recent studies have shown correlations between OGM and alterations of some brain regions by using task-state functional magnetic resonance imaging (fMRI). However, the correlation between OGM and spontaneous brain activity in depression remains unclear. The purpose of this study was to determine whether patients with major depressive disorder (MDD) show abnormal regional homogeneity (ReHo) and, if so, whether the brain areas with abnormal ReHo are associated with OGM. Twenty five patients with MDD and 25 age-matched, sex-matched, and education-matched healthy controls underwent resting-state fMRI. All participants were also assessed by 17-item Hamilton Depression Rating Scale and autobiographical memory test. The ReHo method was used to analyze regional synchronization of spontaneous neuronal activity. Patients with MDD, compared to healthy controls, exhibited extensive ReHo abnormalities in some brain regions, including the frontal, temporal, and occipital cortex. Moreover, ReHo value of the orbitofrontal cortex was negatively correlated with OGM scores in patients with MDD. The sample size of this study was relatively small, and the influence of physiological noise was not completely excluded. These results suggest that abnormal ReHo of spontaneous brain activity in the orbitofrontal cortex may be involved in the pathophysiology of OGM in patients with MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

PubMed Central

Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

2015-01-01

While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

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

PubMed

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

2018-02-01

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

Acute lesions that impair affective empathy

PubMed Central

Oishi, Kenichi; Hsu, John; Lindquist, Martin; Gottesman, Rebecca F.; Jarso, Samson; Crainiceanu, Ciprian; Mori, Susumu

2013-01-01

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy. PMID:23824490

Orbitofrontal sulcogyral patterns are related to temperamental risk for psychopathology.

PubMed

Whittle, Sarah; Bartholomeusz, Cali; Yücel, Murat; Dennison, Meg; Vijayakumar, Nandita; Allen, Nicholas B

2014-02-01

There are marked individual differences in the pattern of cortical (sulcogyral) folding in the orbitofrontal cortex (OFC), and there is a growing literature suggesting that these individual differences are associated with risk for psychotic disorders. To date, however, no study has investigated whether OFC folding patterns are associated with broader risk factors relevant to a range of psychopathology. This study helps address this knowledge gap by examining whether OFC sulcogyral folding patterns are associated with putative risk factors, specifically affective temperament and psychiatric symptoms, in a large community sample (N = 152) of adolescents. Results showed that the most common pattern of folding ('Type I', marked by discontinuity of the medial orbital sulcus and continuity of the lateral orbital sulcus) was associated with low levels of Surgency, high levels of Negative Affectivity (in girls) and higher depressive symptoms. This pattern was also associated with reduced thickness of OFC gray matter. Overall, the findings, combined with previous work, suggest some specificity of neurodevelopmental risk for different types of psychopathology. Thus, these results have the potential to inform the early identification of at-risk individuals.

Effects of transcranial direct current stimulation on craving, heart-rate variability and prefrontal hemodynamics during smoking cue exposure.

PubMed

Kroczek, A M; Häußinger, F B; Rohe, T; Schneider, S; Plewnia, C; Batra, A; Fallgatter, A J; Ehlis, A-C

2016-11-01

Drug-related cue exposure elicits craving and risk for relapse during recovery. Transcranial direct current stimulation is a promising research tool and possible treatment for relapse prevention. Enhanced functional neuroconnectivity is discussed as a treatment target. The goal of this research was to examine whether transcranial direct current stimulation affected cortical hemodynamic indicators of functional connectivity, craving, and heart rate variability during smoking-related cue exposure in non-treatment-seeking smokers. In vivo smoking cue exposure supported by a 2mA transcranial direct current stimulation (anode: dorsolateral prefrontal cortex, cathode: orbitofrontal cortex; placebo-controlled, randomized, double-blind) in 29 (age: M=25, SD=5) German university students (smoking at least once a week). Cue reactivity was assessed on an autonomous (heart rate variability) and a subjective level (craving ratings). Functional near-infrared spectroscopy measured changes in the concentration of deoxygenated hemoglobin, and seed-based correlation analysis was used to quantify prefrontal connectivity of brain regions involved in cue reactivity. Cue exposure elicited increased subjective craving and heart rate variability changes in smokers. Connectivity between the orbitofrontal and dorsolateral prefrontal cortex was increased in subjects receiving verum compared to placebo stimulation (d=0.66). Hemodynamics in the left dorsolateral prefrontal cortex, however, increased in the group receiving sham stimulation (η 2 =0.140). Transcranial direct current stimulation did not significantly alter craving or heart rate variability during cue exposure. Prefrontal connectivity - between regions involved in the processing of reinforcement value and cognitive control - was increased by anodal transcranial direct current stimulation during smoking cue exposure. Possible clinical implications should be considered in future studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neural correlates of affective influence on choice.

PubMed

Piech, Richard M; Lewis, Jade; Parkinson, Caroline H; Owen, Adrian M; Roberts, Angela C; Downing, Paul E; Parkinson, John A

2010-03-01

Making the right choice depends crucially on the accurate valuation of the available options in the light of current needs and goals of an individual. Thus, the valuation of identical options can vary considerably with motivational context. The present study investigated the neural structures underlying context dependent evaluation. We instructed participants to choose from food menu items based on different criteria: on their anticipated taste or on ease of preparation. The aim of the manipulation was to assess which neural sites were activated during choice guided by incentive value, and which during choice based on a value-irrelevant criterion. To assess the impact of increased motivation, affect-guided choice and cognition-guided choice was compared during the sated and hungry states. During affective choice, we identified increased activity in structures representing primarily valuation and taste (medial prefrontal cortex, insula). During cognitive choice, structures showing increased activity included those implicated in suppression and conflict monitoring (lateral orbitofrontal cortex, anterior cingulate). Hunger influenced choice-related activity in the ventrolateral prefrontal cortex. Our results show that choice is associated with the use of distinct neural structures for the pursuit of different goals. Published by Elsevier Inc.

Interactive effects of trait and state affect on top-down control of attention

PubMed Central

Hur, Juyoen; Miller, Gregory A.; McDavitt, Jenika R.B.; Spielberg, Jeffrey M.; Crocker, Laura D.; Infantolino, Zachary P.; Towers, David N.; Warren, Stacie L.

2015-01-01

Few studies have investigated how attentional control is affected by transient affective states while taking individual differences in affective traits into consideration. In this study, participants completed a color-word Stroop task immediately after undergoing a positive, neutral or negative affective context manipulation (ACM). Behavioral performance was unaffected by any ACM considered in isolation. For individuals high in trait negative affect (NA), performance was impaired by the negative but not the positive or neutral ACM. Neuroimaging results indicate that activity in primarily top-down control regions of the brain (inferior frontal gyrus and dorsal anterior cingulate cortex) was suppressed in the presence of emotional arousal (both negative and positive ACMs). This effect appears to have been exacerbated or offset by co-occurring activity in other top-down control regions (parietal) and emotion processing regions (orbitofrontal cortex, amygdala and nucleus accumbens) as a function of the valence of state affect (positive or negative) and trait affect (trait NA or trait PA). Neuroimaging results are consistent with behavioral findings. In combination, they indicate both additive and interactive influences of trait and state affect on top-down control of attention. PMID:25556211

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

2015-06-30

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Differential Encoding of Time by Prefrontal and Striatal Network Dynamics.

PubMed

Bakhurin, Konstantin I; Goudar, Vishwa; Shobe, Justin L; Claar, Leslie D; Buonomano, Dean V; Masmanidis, Sotiris C

2017-01-25

Telling time is fundamental to many forms of learning and behavior, including the anticipation of rewarding events. Although the neural mechanisms underlying timing remain unknown, computational models have proposed that the brain represents time in the dynamics of neural networks. Consistent with this hypothesis, changing patterns of neural activity dynamically in a number of brain areas-including the striatum and cortex-has been shown to encode elapsed time. To date, however, no studies have explicitly quantified and contrasted how well different areas encode time by recording large numbers of units simultaneously from more than one area. Here, we performed large-scale extracellular recordings in the striatum and orbitofrontal cortex of mice that learned the temporal relationship between a stimulus and a reward and reported their response with anticipatory licking. We used a machine-learning algorithm to quantify how well populations of neurons encoded elapsed time from stimulus onset. Both the striatal and cortical networks encoded time, but the striatal network outperformed the orbitofrontal cortex, a finding replicated both in simultaneously and nonsimultaneously recorded corticostriatal datasets. The striatal network was also more reliable in predicting when the animals would lick up to ∼1 s before the actual lick occurred. Our results are consistent with the hypothesis that temporal information is encoded in a widely distributed manner throughout multiple brain areas, but that the striatum may have a privileged role in timing because it has a more accurate "clock" as it integrates information across multiple cortical areas. The neural representation of time is thought to be distributed across multiple functionally specialized brain structures, including the striatum and cortex. However, until now, the neural code for time has not been compared quantitatively between these areas. Here, we performed large-scale recordings in the striatum and orbitofrontal cortex of mice trained on a stimulus-reward association task involving a delay period and used a machine-learning algorithm to quantify how well populations of simultaneously recorded neurons encoded elapsed time from stimulus onset. We found that, although both areas encoded time, the striatum consistently outperformed the orbitofrontal cortex. These results suggest that the striatum may refine the code for time by integrating information from multiple inputs. Copyright © 2017 the authors 0270-6474/17/370854-17$15.00/0.

Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

PubMed

Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Takahashi, Shoki; Mori, Etsuro

2011-07-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age- and gender-matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole-brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel-based morphometry. The PWS subjects showed small gray-matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray-matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas. Copyright © 2010 Wiley-Liss, Inc.

Linking dynamic patterns of neural activity in orbitofrontal cortex with decision making.

PubMed

Rich, Erin L; Stoll, Frederic M; Rudebeck, Peter H

2018-04-01

Humans and animals demonstrate extraordinary flexibility in choice behavior, particularly when deciding based on subjective preferences. We evaluate options on different scales, deliberate, and often change our minds. Little is known about the neural mechanisms that underlie these dynamic aspects of decision-making, although neural activity in orbitofrontal cortex (OFC) likely plays a central role. Recent evidence from studies in macaques shows that attention modulates value responses in OFC, and that ensembles of OFC neurons dynamically signal different options during choices. When contexts change, these ensembles flexibly remap to encode the new task. Determining how these dynamic patterns emerge and relate to choices will inform models of decision-making and OFC function. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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

2016-01-01

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

Increased Cortical Thickness in Male-to-Female Transsexualism

PubMed Central

Luders, Eileen; Sánchez, Francisco J.; Tosun, Duygu; Shattuck, David W.; Gaser, Christian; Vilain, Eric; Toga, Arthur W.

2013-01-01

Background The degree to which one identifies as male or female has a profound impact on one’s life. Yet, there is a limited understanding of what contributes to this important characteristic termed gender identity. In order to reveal factors influencing gender identity, studies have focused on people who report strong feelings of being the opposite sex, such as male-to-female (MTF) transsexuals. Method To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males. Results Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus). Conclusion These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men. PMID:23724358

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset

PubMed Central

Jackson, Stacey A. W.; Horst, Nicole K.; Pears, Andrew; Robbins, Trevor W.; Roberts, Angela C.

2016-01-01

Two learning mechanisms contribute to decision-making: goal-directed actions and the “habit” system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. PMID:27130662

Inefficiency in Self-organized Attentional Switching in the Normal Aging Population is Associated with Decreased Activity in the Ventrolateral Prefrontal Cortex

PubMed Central

Hampshire, Adam; Gruszka, Aleksandra; Fallon, Sean J.; Owen, Adrian M.

2010-01-01

Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top–down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage. PMID:18345987

Decreased gray matter volume of the medial orbitofrontal cortex in panic disorder with agoraphobia: a preliminary study.

PubMed

Na, Kyoung-Sae; Ham, Byung-Joo; Lee, Min-Soo; Kim, Leen; Kim, Yong-Ku; Lee, Heon-Jeong; Yoon, Ho-Kyoung

2013-08-01

Patients with panic disorder with agoraphobia (PDA) have clinical symptoms such as the fear of being outside or of open spaces from which escape would be difficult. Although recent neurobiological studies have suggested that fear conditioning and extinction are associated with PDA, no study has examined the possible structural abnormalities in patients with PDA. This preliminary study compares the gray matter volume among patients with PDA, those with panic disorder without agoraphobia (PDW), and healthy controls (HC) using high-resolution 3.0 T magnetic resonance imaging (MRI) with voxel-based morphometry (VBM). Compared with HC, patients with PDA showed decreased gray matter volume in their left medial orbitofrontal gyrus. However, differences were not found in the gray matter volumes of patients with PDW and whole panic disorder compared with HC. These findings suggest that the phobic avoidance found in patients with PDA arise from abnormalities in the medial orbitofrontal cortex, which plays an important role in fear extinction. Future studies should investigate the neuroanatomical substrates of PDA and distinguish them from those of PDW. Copyright © 2013 Elsevier Inc. All rights reserved.

Orbitofrontal cortex function and structure in depression.

PubMed

Drevets, Wayne C

2007-12-01

The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

A human chemosignal modulates frontolimbic activity and connectivity in response to emotional stimuli.

PubMed

Hummer, Tom A; Phan, K Luan; Kern, David W; McClintock, Martha K

2017-01-01

Evidence suggests the putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a natural component of human sweat, increases attention to emotional information when passively inhaled, even in minute amounts. However, the neural mechanisms underlying androstadienone's impact on the perception of emotional stimuli have not been clarified. To characterize how the compound modifies neural circuitry while attending to emotional information, 22 subjects (11 women) underwent two fMRI scanning sessions, one with an androstadienone solution and one with a carrier control solution alone on their upper lip. During each session, participants viewed blocks of emotionally positive, negative, or neutral images. The BOLD response to emotional images (relative to neutral images) was greater during exposure to androstadienone in right orbitofrontal and lateral prefrontal cortex, particularly during positive image blocks. Androstadienone did not impact the response to social images, compared to nonsocial images, and results were not related to participant sex or olfactory sensitivity. To examine how androstadienone influences effective connectivity of this network, a dynamic causal model was employed with primary visual cortex (V1), amygdala, prefrontal cortex, and orbitofrontal cortex on each side. These models indicated that emotional images increased the drive from V1 to the amygdala during the control session. With androstadienone present, this drive to amygdala was decreased specifically for positive images, which drove downstream increases in orbitofrontal and prefrontal activity. This evidence suggests that androstadienone may act as a chemical signal to increase attention to positively valenced information via modifications to amygdala connectivity. Copyright © 2016. Published by Elsevier Ltd.

Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.

PubMed

Zikopoulos, Basilis; Höistad, Malin; John, Yohan; Barbas, Helen

2017-05-17

The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders. SIGNIFICANCE STATEMENT The dialogue between prefrontal cortex and amygdala allows thoughts and emotions to influence actions. The posterior orbitofrontal cortex sends a powerful pathway that targets a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose wiring may help modulate autonomic function. By contrast, the anterior cingulate cortex innervates other amygdalar parts, activating circuits to help avoid danger. Most IM neurons in primates label for the protein DARPP-32, known to be activated or inhibited based on the level of dopamine. Stress markedly increases dopamine release and inhibits IM neurons, compromises prefrontal control of the amygdala, and sets off a general alarm system as seen in affective disorders, such as chronic anxiety and post-traumatic stress disorder. Copyright © 2017 the authors 0270-6474/17/375051-14$15.00/0.

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

Lasting impact of regret and gratification on resting brain activity and its relation to depressive traits.

PubMed

Eryilmaz, Hamdi; Van De Ville, Dimitri; Schwartz, Sophie; Vuilleumier, Patrik

2014-06-04

Obtaining lower gains than rejected alternatives during decision making evokes feelings of regret, whereas higher gains elicit gratification. Although decision-related emotions produce lingering effects on mental state, neuroscience research has generally focused on transient brain responses to positive or negative events, but ignored more sustained consequences of emotional episodes on subsequent brain states. We investigated how spontaneous brain activity and functional connectivity at rest are modulated by postdecision regret and gratification in 18 healthy human subjects using a gambling task in fMRI. Differences between obtained and unobtained outcomes were manipulated parametrically to evoke different levels of regret or gratification. We investigated how individual personality traits related to depression and rumination affected these responses. Medial and ventral prefrontal areas differentially responded to favorable and unfavorable outcomes during the gambling period. More critically, during subsequent rest, rostral anterior and posterior cingulate cortex, ventral striatum, and insula showed parametric response to the gratification level of preceding outcomes. Functional coupling of posterior cingulate with striatum and amygdala was also enhanced during rest after high gratification. Regret produced distinct changes in connectivity of subgenual cingulate with orbitofrontal cortex and thalamus. Interestingly, individual differences in depressive traits and ruminations correlated with activity of the striatum after gratification and orbitofrontal cortex after regret, respectively. By revealing lingering effects of decision-related emotions on key nodes of resting state networks, our findings illuminate how such emotions may influence self-reflective processing and subsequent behavioral adjustment, but also highlight the malleability of resting networks in emotional contexts. Copyright © 2014 the authors 0270-6474/14/347825-11$15.00/0.

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.

Motivation but not valence modulates neuroticism-dependent cingulate cortex and insula activity.

PubMed

Deng, Yaling; Li, Shijia; Zhou, Renlai; Walter, Martin

2018-04-01

Neuroticism has been found to specifically modulate amygdala activations during differential processing of valence and motivation while other brain networks yet are unexplored for associated effects. The main purpose of this study was to investigate whether neural mechanisms processing valence or motivation are prone to neuroticism in the salience network (SN), a network that is anchored in the anterior cingulate cortex (ACC) and the anterior insula. This study used functional magnetic resonance imaging (fMRI) and an approach/avoid emotional pictures task to investigate brain activations modulated by pictures' valence or motivational status between high and low neurotic individuals. We found that neuroticism-dependent SN and the parahippocampal-fusiform area activations were modulated by motivation but not valence. Valence in contrast interacted with neuroticism in the lateral orbitofrontal cortex. We suggested that neuroticism modulated valence and motivation processing, however, under the influence of the two distinct networks. Neuroticism modulated the motivation through the SN while it modulated the valence through the orbitofrontal networks. © 2018 Wiley Periodicals, Inc.

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.

Lateral orbitofrontal cortex links social impressions to political choices.

PubMed

Xia, Chenjie; Stolle, Dietlind; Gidengil, Elisabeth; Fellows, Lesley K

2015-06-03

Recent studies of political behavior suggest that voting decisions can be influenced substantially by "first-impression" social attributions based on physical appearance. Separate lines of research have implicated the orbitofrontal cortex (OFC) in the judgment of social traits on the one hand and economic decision-making on the other, making this region a plausible candidate for linking social attributions to voting decisions. Here, we asked whether OFC lesions in humans disrupted the ability to judge traits of political candidates or affected how these judgments influenced voting decisions. Seven patients with lateral OFC damage, 18 patients with frontal damage sparing the lateral OFC, and 53 matched healthy participants took part in a simulated election paradigm, in which they voted for real-life (but unknown) candidates based only on photographs of their faces. Consistent with previous work, attributions of "competence" and "attractiveness" based on candidate appearance predicted voting behavior in the healthy control group. Frontal damage did not affect substantially the ability to make competence or attractiveness judgments, but patients with damage to the lateral OFC differed from other groups in how they applied this information when voting. Only attractiveness ratings had any predictive power for voting choices after lateral OFC damage, whereas other frontal patients and healthy controls relied on information about both competence and attractiveness in making their choice. An intact lateral OFC may not be necessary for judgment of social traits based on physical appearance, but it seems to be crucial in applying this information in political decision-making. Copyright © 2015 the authors 0270-6474/15/358507-08$15.00/0.

Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task

PubMed Central

Janitzky, Kathrin; Lippert, Michael T.; Engelhorn, Achim; Tegtmeier, Jennifer; Goldschmidt, Jürgen; Heinze, Hans-Jochen; Ohl, Frank W.

2015-01-01

The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks. PMID:26582980

The neural representation of typical and atypical experiences of negative images: comparing fear, disgust and morbid fascination

PubMed Central

Lindquist, Kristen A.; Adebayo, Morenikeji; Barrett, Lisa Feldman

2016-01-01

Negative stimuli do not only evoke fear or disgust, but can also evoke a state of ‘morbid fascination’ which is an urge to approach and explore a negative stimulus. In the present neuroimaging study, we applied an innovative method to investigate the neural systems involved in typical and atypical conceptualizations of negative images. Participants received false feedback labeling their mental experience as fear, disgust or morbid fascination. This manipulation was successful; participants judged the false feedback correct for 70% of the trials on average. The neuroimaging results demonstrated differential activity within regions in the ‘neural reference space for discrete emotion’ depending on the type of feedback. We found robust differences in the ventrolateral prefrontal cortex, the dorsomedial prefrontal cortex and the lateral orbitofrontal cortex comparing morbid fascination to control feedback. More subtle differences in the dorsomedial prefrontal cortex and the lateral orbitofrontal cortex were also found between morbid fascination feedback and the other emotion feedback conditions. This study is the first to forward evidence about the neural representation of the experimentally unexplored state of morbid fascination. In line with a constructionist framework, our findings suggest that neural resources associated with the process of conceptualization contribute to the neural representation of this state. PMID:26180088

Interactive effects of trait and state affect on top-down control of attention.

PubMed

Hur, Juyoen; Miller, Gregory A; McDavitt, Jenika R B; Spielberg, Jeffrey M; Crocker, Laura D; Infantolino, Zachary P; Towers, David N; Warren, Stacie L; Heller, Wendy

2015-08-01

Few studies have investigated how attentional control is affected by transient affective states while taking individual differences in affective traits into consideration. In this study, participants completed a color-word Stroop task immediately after undergoing a positive, neutral or negative affective context manipulation (ACM). Behavioral performance was unaffected by any ACM considered in isolation. For individuals high in trait negative affect (NA), performance was impaired by the negative but not the positive or neutral ACM. Neuroimaging results indicate that activity in primarily top-down control regions of the brain (inferior frontal gyrus and dorsal anterior cingulate cortex) was suppressed in the presence of emotional arousal (both negative and positive ACMs). This effect appears to have been exacerbated or offset by co-occurring activity in other top-down control regions (parietal) and emotion processing regions (orbitofrontal cortex, amygdala and nucleus accumbens) as a function of the valence of state affect (positive or negative) and trait affect (trait NA or trait PA). Neuroimaging results are consistent with behavioral findings. In combination, they indicate both additive and interactive influences of trait and state affect on top-down control of attention. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Disruption of relative reward value by reversible disconnection of orbitofrontal and rhinal cortex using DREADDs in rhesus monkeys

PubMed Central

Eldridge, Mark A G; Lerchner, Walter; Saunders, Richard C; Kaneko, Hiroyuki; Krausz, Kristopher W; Gonzalez, Frank J; Ji, Bin; Higuchi, Makoto; Minamimoto, Takafumi; Richmond, Barry J

2015-01-01

To study how the interaction between orbitofrontal (OFC) and rhinal (Rh) cortices influences the judgment of reward size, we reversibly disconnected these regions using the hM4Di-DREADD (Designer Receptor Exclusively Activated by Designer Drug). Repeated inactivation reduced sensitivity to differences in reward size in two monkeys. Results suggest that retrieval of relative stimulus values from memory appears to depend on interaction between Rh and OFC. PMID:26656645

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

PubMed

Shamay-Tsoory, S G; Tomer, R; Berger, B D; Goldsher, D; Aharon-Peretz, J

2005-03-01

To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations.

PubMed

Lichtenberg, Nina T; Pennington, Zachary T; Holley, Sandra M; Greenfield, Venuz Y; Cepeda, Carlos; Levine, Michael S; Wassum, Kate M

2017-08-30

To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g., stimuli or available actions) to retrieve often quite detailed memories of available rewards. The basolateral amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key nodes in the circuitry supporting such outcome-guided behaviors. But there is much unknown about the contribution of this circuit to decision making, and almost nothing known about the whether any contribution is via direct, monosynaptic projections, or the direction of information transfer. Therefore, here we used designer receptor-mediated inactivation of OFC→BLA or BLA→OFC projections to evaluate their respective contributions to outcome-guided behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC terminals in the BLA, disrupted the selective motivating influence of cue-triggered reward representations over reward-seeking decisions as assayed by Pavlovian-to-instrumental transfer. BLA→OFC projections were also required when a cued reward representation was used to modify Pavlovian conditional goal-approach responses according to the reward's current value. These projections were not necessary when actions were guided by reward expectations generated based on learned action-reward contingencies, or when rewards themselves, rather than stored memories, directed action. These data demonstrate that BLA→OFC projections enable the cue-triggered reward expectations that can motivate the execution of specific action plans and allow adaptive conditional responding. SIGNIFICANCE STATEMENT Deficits anticipating potential future rewarding events are associated with many psychiatric diseases. Presently, we know little about the neural circuits supporting such reward expectation. Here we show that basolateral amygdala to orbitofrontal cortex projections are required for expectations of specific available rewards to influence reward seeking and decision making. The necessity of these projections was limited to situations in which expectations were elicited by reward-predictive cues. These projections therefore facilitate adaptive behavior by enabling the orbitofrontal cortex to use environmental stimuli to generate expectations of potential future rewarding events. Copyright © 2017 the authors 0270-6474/17/378374-11$15.00/0.

Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations

PubMed Central

Lichtenberg, Nina T.; Pennington, Zachary T.; Holley, Sandra M.; Greenfield, Venuz Y.; Levine, Michael S.

2017-01-01

To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g., stimuli or available actions) to retrieve often quite detailed memories of available rewards. The basolateral amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key nodes in the circuitry supporting such outcome-guided behaviors. But there is much unknown about the contribution of this circuit to decision making, and almost nothing known about the whether any contribution is via direct, monosynaptic projections, or the direction of information transfer. Therefore, here we used designer receptor-mediated inactivation of OFC→BLA or BLA→OFC projections to evaluate their respective contributions to outcome-guided behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC terminals in the BLA, disrupted the selective motivating influence of cue-triggered reward representations over reward-seeking decisions as assayed by Pavlovian-to-instrumental transfer. BLA→OFC projections were also required when a cued reward representation was used to modify Pavlovian conditional goal-approach responses according to the reward's current value. These projections were not necessary when actions were guided by reward expectations generated based on learned action-reward contingencies, or when rewards themselves, rather than stored memories, directed action. These data demonstrate that BLA→OFC projections enable the cue-triggered reward expectations that can motivate the execution of specific action plans and allow adaptive conditional responding. SIGNIFICANCE STATEMENT Deficits anticipating potential future rewarding events are associated with many psychiatric diseases. Presently, we know little about the neural circuits supporting such reward expectation. Here we show that basolateral amygdala to orbitofrontal cortex projections are required for expectations of specific available rewards to influence reward seeking and decision making. The necessity of these projections was limited to situations in which expectations were elicited by reward-predictive cues. These projections therefore facilitate adaptive behavior by enabling the orbitofrontal cortex to use environmental stimuli to generate expectations of potential future rewarding events. PMID:28743727

Mapping aesthetic musical emotions in the brain.

PubMed

Trost, Wiebke; Ethofer, Thomas; Zentner, Marcel; Vuilleumier, Patrik

2012-12-01

Music evokes complex emotions beyond pleasant/unpleasant or happy/sad dichotomies usually investigated in neuroscience. Here, we used functional neuroimaging with parametric analyses based on the intensity of felt emotions to explore a wider spectrum of affective responses reported during music listening. Positive emotions correlated with activation of left striatum and insula when high-arousing (Wonder, Joy) but right striatum and orbitofrontal cortex when low-arousing (Nostalgia, Tenderness). Irrespective of their positive/negative valence, high-arousal emotions (Tension, Power, and Joy) also correlated with activations in sensory and motor areas, whereas low-arousal categories (Peacefulness, Nostalgia, and Sadness) selectively engaged ventromedial prefrontal cortex and hippocampus. The right parahippocampal cortex activated in all but positive high-arousal conditions. Results also suggested some blends between activation patterns associated with different classes of emotions, particularly for feelings of Wonder or Transcendence. These data reveal a differentiated recruitment across emotions of networks involved in reward, memory, self-reflective, and sensorimotor processes, which may account for the unique richness of musical emotions.

Mapping Aesthetic Musical Emotions in the Brain

PubMed Central

Ethofer, Thomas; Zentner, Marcel; Vuilleumier, Patrik

2012-01-01

Music evokes complex emotions beyond pleasant/unpleasant or happy/sad dichotomies usually investigated in neuroscience. Here, we used functional neuroimaging with parametric analyses based on the intensity of felt emotions to explore a wider spectrum of affective responses reported during music listening. Positive emotions correlated with activation of left striatum and insula when high-arousing (Wonder, Joy) but right striatum and orbitofrontal cortex when low-arousing (Nostalgia, Tenderness). Irrespective of their positive/negative valence, high-arousal emotions (Tension, Power, and Joy) also correlated with activations in sensory and motor areas, whereas low-arousal categories (Peacefulness, Nostalgia, and Sadness) selectively engaged ventromedial prefrontal cortex and hippocampus. The right parahippocampal cortex activated in all but positive high-arousal conditions. Results also suggested some blends between activation patterns associated with different classes of emotions, particularly for feelings of Wonder or Transcendence. These data reveal a differentiated recruitment across emotions of networks involved in reward, memory, self-reflective, and sensorimotor processes, which may account for the unique richness of musical emotions. PMID:22178712

Immediate and delayed neuroendocrine responses to social exclusion in males and females.

PubMed

Radke, S; Seidel, E M; Boubela, R N; Thaler, H; Metzler, H; Kryspin-Exner, I; Moser, E; Habel, U; Derntl, B

2018-07-01

Social exclusion is a complex phenomenon, with wide-ranging immediate and delayed effects on well-being, hormone levels, brain activation and motivational behavior. Building upon previous work, the current fMRI study investigated affective, endocrine and neural responses to social exclusion in a more naturalistic Cyberball task in 40 males and 40 females. As expected, social exclusion elicited well-documented affective and neural responses, i.e., increased anger and distress, as well as increased exclusion-related activation of the anterior insula, the posterior-medial frontal cortex and the orbitofrontal cortex. Cortisol and testosterone decreased over the course of the experiment, whereas progesterone showed no changes. Hormone levels were not correlated with subjective affect, but they were related to exclusion-induced neural responses. Exclusion-related activation in frontal areas was associated with decreases in cortisol and increases in testosterone until recovery. Given that results were largely independent of sex, the current findings have important implications regarding between-sex vs. within-sex variations and the conceptualization of state vs. trait neuroendocrine functions in social neuroscience. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-tensor investigation of orbitofrontal cortex tracts affected in subcaudate tractotomy.

PubMed

Yang, Jimmy C; Papadimitriou, George; Eckbo, Ryan; Yeterian, Edward H; Liang, Lichen; Dougherty, Darin D; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha; Kubicki, Marek; Eskandar, Emad N; Makris, Nikos

2015-06-01

Subcaudate tractotomy (SCT) is a neurosurgical lesioning procedure that can reduce symptoms in medically intractable obsessive compulsive disorder (OCD). Due to the putative importance of the orbitofrontal cortex (OFC) in symptomatology, fibers that connect the OFC, SCT lesion, and either the thalamus or brainstem were investigated with two-tensor tractography using an unscented Kalman filter approach. From this dataset, fibers were warped to Montreal Neurological Institute space, and probability maps with center-of-mass analysis were subsequently generated. In comparing fibers from the same OFC region, including medial OFC (mOFC), central OFC (cOFC), and lateral OFC (lOFC), the area of divergence for fibers connected with the thalamus versus the brainstem is posterior to the anterior commissure. At the anterior commissure, fibers connected with the thalamus run dorsal to those connected with the brainstem. As OFC fibers travel through the ventral aspect of the internal capsule, lOFC fibers are dorsal to cOFC and mOFC fibers. Using neuroanatomical comparison, tracts coursing between the OFC and thalamus are likely part of the anterior thalamic radiations, while those between the OFC and brainstem likely belong to the medial forebrain bundle. These data support the involvement of the OFC in OCD and may be relevant to creating differential lesional procedures of specific tracts or to developing deep brain stimulation programming paradigms.

(S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling.

PubMed

Sladky, Ronald; Spies, Marie; Hoffmann, Andre; Kranz, Georg; Hummer, Allan; Gryglewski, Gregor; Lanzenberger, Rupert; Windischberger, Christian; Kasper, Siegfried

2015-03-01

Citalopram and Escitalopram are gold standard pharmaceutical treatment options for affective, anxiety, and other psychiatric disorders. However, their neurophysiologic function on cortico-limbic circuits is incompletely characterized. Here we studied the neuropharmacological influence of Citalopram and Escitalopram on cortico-limbic regulatory processes by assessing the effective connectivity between orbitofrontal cortex (OFC) and amygdala using dynamic causal modeling (DCM) applied to functional MRI data. We investigated a cohort of 15 healthy subjects in a randomized, crossover, double-blind design after 10days of Escitalopram (10mg/d (S)-citalopram), Citalopram (10mg/d (S)-citalopram and 10mg/d (R)-citalopram), or placebo. Subjects performed an emotional face discrimination task, while undergoing functional magnetic resonance imaging (fMRI) scanning at 3 Tesla. As hypothesized, the OFC, in the context of the emotional face discrimination task, exhibited a down-regulatory effect on amygdala activation. This modulatory effect was significantly increased by (S)-citalopram, but not (R)-citalopram. For the first time, this study shows that (1) the differential effects of the two enantiomers (S)- and (R)-citalopram on cortico-limbic connections can be demonstrated by modeling effective connectivity methods, and (2) one of their mechanisms can be linked to an increased inhibition of amygdala activation by the orbitofrontal cortex. Copyright © 2014 Elsevier Inc. All rights reserved.

Switching brain serotonin with oxytocin.

PubMed

Mottolese, Raphaelle; Redouté, Jérôme; Costes, Nicolas; Le Bars, Didier; Sirigu, Angela

2014-06-10

Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human affect and sociality and in disorders like depression and autism. We asked whether these chemical messengers interact in the regulation of emotion-based behavior by administering OXT or placebo to 24 healthy subjects and mapping cerebral 5-HT system by using 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), an antagonist of 5-HT1A receptors. OXT increased [(18)F]MPPF nondisplaceable binding potential (BPND) in the dorsal raphe nucleus (DRN), the core area of 5-HT synthesis, and in the amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the amygdala appears central in the regulation of 5-HT by OXT: [(18)F]MPPF BPND changes in the DRN correlated with changes in right amygdala, which were in turn correlated with changes in hippocampus, insula, subgenual, and orbitofrontal cortex, a circuit implicated in the control of stress, mood, and social behaviors. OXT administration is known to inhibit amygdala activity and results in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation have been associated with increased anxiety. The present study reveals a previously unidentified form of interaction between these two systems in the human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT signaling, which could lead to novel therapeutic strategies for mental disorders.

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.

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

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset.

PubMed

Jackson, Stacey A W; Horst, Nicole K; Pears, Andrew; Robbins, Trevor W; Roberts, Angela C

2016-07-01

Two learning mechanisms contribute to decision-making: goal-directed actions and the "habit" system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. © The Author 2016. Published by Oxford University Press.

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

PubMed

Márquez, C; Poirier, G L; Cordero, M I; Larsen, M H; Groner, A; Marquis, J; Magistretti, P J; Trono, D; Sandi, C

2013-01-15

Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress with face, construct and predictive validity. We show that male rats submitted to fear-induction experiences during the peripubertal period exhibit high and sustained rates of increased aggression at adulthood, even against unthreatening individuals, and increased testosterone/corticosterone ratio. They also exhibit hyperactivity in the amygdala under both basal conditions (evaluated by 2-deoxy-glucose autoradiography) and after a resident-intruder (RI) test (evaluated by c-Fos immunohistochemistry), and hypoactivation of the medial orbitofrontal (MO) cortex after the social challenge. Alterations in the connectivity between the orbitofrontal cortex and the amygdala were linked to the aggressive phenotype. Increased and sustained expression levels of the monoamine oxidase A (MAOA) gene were found in the prefrontal cortex but not in the amygdala of peripubertally stressed animals. They were accompanied by increased activatory acetylation of histone H3, but not H4, at the promoter of the MAOA gene. Treatment with an MAOA inhibitor during adulthood reversed the peripuberty stress-induced antisocial behaviors. Beyond the characterization and validation of the model, we present novel data highlighting changes in the serotonergic system in the prefrontal cortex-and pointing at epigenetic control of the MAOA gene-in the establishment of the link between peripubertal stress and later pathological aggression. Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence of violent behaviors.

The role of emotion in decision-making: evidence from neurological patients with orbitofrontal damage.

PubMed

Bechara, Antoine

2004-06-01

Most theories of choice assume that decisions derive from an assessment of the future outcomes of various options and alternatives through some type of cost-benefit analyses. The influence of emotions on decision-making is largely ignored. The studies of decision-making in neurological patients who can no longer process emotional information normally suggest that people make judgments not only by evaluating the consequences and their probability of occurring, but also and even sometimes primarily at a gut or emotional level. Lesions of the ventromedial (which includes the orbitofrontal) sector of the prefrontal cortex interfere with the normal processing of "somatic" or emotional signals, while sparing most basic cognitive functions. Such damage leads to impairments in the decision-making process, which seriously compromise the quality of decisions in daily life. The aim of this paper is to review evidence in support of "The Somatic Marker Hypothesis," which provides a systems-level neuroanatomical and cognitive framework for decision-making and suggests that the process of decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion, and feeling. The implications of this theoretical framework for the normal and abnormal development of the orbitofrontal cortex are also discussed.

[Neural Mechanisms Underlying the Processing of Temporal Information in Episodic Memory and Its Disturbance].

PubMed

Iwata, Saeko; Tsukiura, Takashi

2017-11-01

Episodic memory is defined as memory for personally experienced events, and includes memory content and contextual information of time and space. Previous neuroimaging and neuropsychological studies have demonstrated three possible roles of the temporal context in episodic memory. First, temporal information contributes to the arrangement of temporal order for sequential events in episodic memory, and this process is involved in the lateral prefrontal cortex. The second possible role of temporal information in episodic memory is the segregation between memories of multiple events, which are segregated by cues of different time information. The role of segregation is associated with the orbitofrontal regions including the orbitofrontal cortex and basal forebrain region. Third, temporal information in episodic memory plays an important role in the integration of multiple components into a coherent episodic memory, in which episodic components in the different modalities are combined by temporal information as an index. The role of integration is mediated by the medial temporal lobe including the hippocampus and parahippocampal gyrus. Thus, temporal information in episodic memory could be represented in multiple stages, which are involved in a network of the lateral prefrontal, orbitofrontal, and medial temporal lobe regions.

Neural correlates of the affect regulation model in schizophrenia patients with substance use history: a functional magnetic resonance imaging study.

PubMed

Mancini-Marïe, Adham; Potvin, Stéphane; Fahim, Cherine; Beauregard, Mario; Mensour, Boualem; Stip, Emmanuel

2006-03-01

The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the etiology of this comorbid condition remains unknown. According to the affect regulation model, schizophrenia patients abuse drugs in order to cope with their negative affects. Supporting the model, clinical studies have shown that dual-diagnosis patients have less blunting of affect and that they experience more negative affect. We hypothesized that patients with a history of substance use would have increased cerebral activations in response to aversive stimuli when compared to abstinent patients. Schizophrenia patients were divided into 2 groups: patients with (SCZ-SU group; N = 12) and without (SCZ group; N = 11) a current or past substance use disorder (alcohol, cannabis, and/or LSD). Diagnoses were made according to DSM-IV criteria. Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of emotionally negative pictures (International Affective Picture System). Data were gathered from September 2001 to December 2003. Subjectively, the emotional experience induced by viewing the negative pictures was rated significantly higher in the SCZ-SU group than in the SCZ group (p = .008). Neurally, in the SCZ-SU group, significant loci of activation were identified in the right medial prefrontal cortex (Brodmann's area [BA] 10), left medial prefrontal cortex (BA 10), right orbitofrontal cortex (BA 47), and left amygdala. No significant loci of activation were observed in the SCZ group. These results suggest that the functioning of the medial prefrontal cortex, thought to be impaired in patients with prominent negative symptoms, is more preserved in dual-diagnosis schizophrenia. This relative preservation could be primary or secondary to substance use.

Structural connectivity of neural reward networks in youth at risk for substance use disorders.

PubMed

Squeglia, Lindsay M; Sorg, Scott F; Jacobus, Joanna; Brumback, Ty; Taylor, Charles T; Tapert, Susan F

2015-07-01

Having a positive family history of alcohol use disorders (FHP), as well as aberrant reward circuitry, has been implicated in the initiation of substance use during adolescence. This study explored the relationship between FHP status and reward circuitry in substance naïve youth to better understand future risky behaviors. Participants were 49 FHP and 45 demographically matched family history negative (FHN) substance-naïve 12-14 year-olds (54 % female). Subjects underwent structural magnetic resonance imaging, including diffusion tensor imaging. Nucleus accumbens and orbitofrontal cortex volumes were derived using FreeSurfer, and FSL probabilistic tractography probed structural connectivity and differences in white matter diffusivity estimates (e.g. fractional anisotropy, and mean, radial, and axial diffusivity) between fiber tracts connecting these regions. FHP and FHN youth did not differ on nucleus accumbens or orbitofrontal cortex volumes, white matter tract volumes, or percentages of streamlines (a proxy for fiber tract count) connecting these regions. However, within white matter tracts connecting the nucleus accumbens to the orbitofrontal cortex, FHP youth had significantly lower mean and radial diffusivity (ps < 0.03) than FHN youth. While white matter macrostructure between salience and reward regions did not differ between FHP and FHN youth, FHP youth showed greater white matter coherence within these tracts than FHN youth. Aberrant connectivity between reward regions in FHP youth could be linked to an increased risk for substance use initiation.

Impaired social response reversal. A case of 'acquired sociopathy'.

PubMed

Blair, R J; Cipolotti, L

2000-06-01

In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with 'acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.

The neural representation of social status in the extended face-processing network.

PubMed

Koski, Jessica E; Collins, Jessica A; Olson, Ingrid R

2017-12-01

Social status is a salient cue that shapes our perceptions of other people and ultimately guides our social interactions. Despite the pervasive influence of status on social behavior, how information about the status of others is represented in the brain remains unclear. Here, we tested the hypothesis that social status information is embedded in our neural representations of other individuals. Participants learned to associate faces with names, job titles that varied in associated status, and explicit markers of reputational status (star ratings). Trained stimuli were presented in an functional magnetic resonance imaging experiment where participants performed a target detection task orthogonal to the variable of interest. A network of face-selective brain regions extending from the occipital lobe to the orbitofrontal cortex was localized and served as regions of interest. Using multivoxel pattern analysis, we found that face-selective voxels in the lateral orbitofrontal cortex - a region involved in social and nonsocial valuation, could decode faces based on their status. Similar effects were observed with two different status manipulations - one based on stored semantic knowledge (e.g., different careers) and one based on learned reputation (e.g., star ranking). These data suggest that a face-selective region of the lateral orbitofrontal cortex may contribute to the perception of social status, potentially underlying the preferential attention and favorable biases humans display toward high-status individuals. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Fronto-temporal white matter connectivity predicts reversal learning errors

PubMed Central

Alm, Kylie H.; Rolheiser, Tyler; Mohamed, Feroze B.; Olson, Ingrid R.

2015-01-01

Each day, we make hundreds of decisions. In some instances, these decisions are guided by our innate needs; in other instances they are guided by memory. Probabilistic reversal learning tasks exemplify the close relationship between decision making and memory, as subjects are exposed to repeated pairings of a stimulus choice with a reward or punishment outcome. After stimulus–outcome associations have been learned, the associated reward contingencies are reversed, and participants are not immediately aware of this reversal. Individual differences in the tendency to choose the previously rewarded stimulus reveal differences in the tendency to make poorly considered, inflexible choices. Lesion studies have strongly linked reversal learning performance to the functioning of the orbitofrontal cortex, the hippocampus, and in some instances, the amygdala. Here, we asked whether individual differences in the microstructure of the uncinate fasciculus, a white matter tract that connects anterior and medial temporal lobe regions to the orbitofrontal cortex, predict reversal learning performance. Diffusion tensor imaging and behavioral paradigms were used to examine this relationship in 33 healthy young adults. The results of tractography revealed a significant negative relationship between reversal learning performance and uncinate axial diffusivity, but no such relationship was demonstrated in a control tract, the inferior longitudinal fasciculus. Our findings suggest that the uncinate might serve to integrate associations stored in the anterior and medial temporal lobes with expectations about expected value based on feedback history, computed in the orbitofrontal cortex. PMID:26150776

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

PubMed

Qiu, Ying-Wei; Lv, Xiao-Fei; Jiang, Gui-Hua; Su, Huan-Huan; Ma, Xiao-Fen; Tian, Jun-Zhang; Zhuo, Fu-Zhen

2017-03-01

To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

A MAOA gene*cocaine severity interaction on impulsivity and neuropsychological measures of orbitofrontal dysfunction: preliminary results.

PubMed

Verdejo-García, Antonio; Albein-Urios, Natalia; Molina, Esther; Ching-López, Ana; Martínez-González, José M; Gutiérrez, Blanca

2013-11-01

Based on previous evidence of a MAOA gene*cocaine use interaction on orbitofrontal cortex volume attrition, we tested whether the MAOA low activity variant and cocaine use severity are interactively associated with impulsivity and behavioral indices of orbitofrontal dysfunction: emotion recognition and decision-making. 72 cocaine dependent individuals and 52 non-drug using controls (including healthy individuals and problem gamblers) were genotyped for the MAOA gene and tested using the UPPS-P Impulsive Behavior Scale, the Iowa Gambling Task and the Ekman's Facial Emotions Recognition Test. To test the main hypothesis, we conducted hierarchical multiple regression analyses including three sets of predictors: (1) age, (2) MAOA genotype and severity of cocaine use, and (3) the interaction between MAOA genotype and severity of cocaine use. UPPS-P, Ekman Test and Iowa Gambling Task's scores were the outcome measures. We computed the statistical significance of the prediction change yielded by each consecutive set, with 'a priori' interest in the MAOA*cocaine severity interaction. We found significant effects of the MAOA gene*cocaine use severity interaction on the emotion recognition scores and the UPPS-P's dimensions of Positive Urgency and Sensation Seeking: Low activity carriers with higher cocaine exposure had poorer emotion recognition and higher Positive Urgency and Sensation Seeking. Cocaine users carrying the MAOA low activity show a greater impact of cocaine use on impulsivity and behavioral measures of orbitofrontal cortex dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Recognition memory for vibrotactile rhythms: an fMRI study in blind and sighted individuals.

PubMed

Sinclair, Robert J; Dixit, Sachin; Burton, Harold

2011-01-01

Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned "old" and "new" rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes.

Recognition memory for vibrotactile rhythms: An fMRI study in blind and sighted individuals

PubMed Central

SINCLAIR, ROBERT J.; DIXIT, SACHIN; BURTON, HAROLD

2014-01-01

Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned “old” and “new” rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes. PMID:21846300

Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus.

PubMed

Alcaraz, Fabien; Marchand, Alain R; Vidal, Elisa; Guillou, Alexandre; Faugère, Angélique; Coutureau, Etienne; Wolff, Mathieu

2015-09-23

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions. Significance statement: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning. Copyright © 2015 the authors 0270-6474/15/3513183-11$15.00/0.

Orbitofrontal disinhibition of pain in migraine with aura: an interictal EEG-mapping study.

PubMed

Lev, Rina; Granovsky, Yelena; Yarnitsky, David

2010-08-01

This study aimed to identify the cortical mechanisms underlying the processes of interictal dishabituation to experimental pain in subjects suffering from migraine with aura (MWA). In 21 subjects with MWA and 22 healthy controls, cortical responses to two successive trials of noxious contact-heat stimuli were analyzed using EEG-tomography software. When compared with controls, MWA patients showed significantly increased pain-evoked potential amplitudes accompanied by reduced activity in the orbitofrontal cortex (OFC) and increased activity in the pain matrix regions, including the primary somatosensory cortex (SI) (p < .05). Similarly to controls, MWA subjects displayed an inverse correlation between the OFC and SI activities, and positive interrelations between other pain-specific regions. The activity changes in the OFC negatively correlated with lifetime headache duration and longevity (p < .05). Reduced inhibitory functioning of the prefrontal cortex is a possible cause for disinhibition of the pain-related sensory cortices in migraine. The finding of OFC hypofunction over the disease course is in keeping with current concepts of migraine as a progressive brain disorder.

Delayed activation of the primary orbitofrontal cortex in post-traumatic anosmia.

PubMed

Lee, Vincent Kyu; Nardone, Raffaele; Wasco, Fern; Panigrahy, Ashok; Zuccoli, Giulio

2016-01-01

Functional magnetic resonance imaging may help in elucidating the pathophysiology of post-traumatic anosmia. Using an fMRI olfactory stimulus paradigm, this study compared BOLD activation of the brain in a 21-year old male research subject with post-traumatic anosmia and a 19-year old male normal healthy control participant. A delayed activation of the primary orbitofrontal cortex was found in the subject with traumatic anosmia, which may represent a crucial pathophysiological mechanism in the subject with traumatic anosmia due to axonal injury or traumatic transection at the lamina cribrosa level. In healthy subjects the activation of secondary cortical areas may be due to the habituation effect in the primary olfactory cortex. This raises the possibility that, in the absence of secondary activation areas-that may act as a feed-back habituation or desensitization in the patient-one of the primary response areas is activated over the longer period of stimulation. The failed activation of these secondary areas in the patient may cause a feed-back habituation or desensitization in the patient and could also play a role in the disturbed perception of odours.

The Neural Correlates of Desire

PubMed Central

Kawabata, Hideaki; Zeki, Semir

2008-01-01

In an event-related fMRI study, we scanned eighteen normal human subjects while they viewed three categories of pictures (events, objects and persons) which they classified according to desirability (desirable, indifferent or undesirable). Each category produced activity in a distinct part of the visual brain, thus reflecting its functional specialization. We used conjunction analysis to learn whether there is a brain area which is always active when a desirable picture is viewed, regardless of the category to which it belongs. The conjunction analysis of the contrast desirable > undesirable revealed activity in the superior orbito-frontal cortex. This activity bore a positive linear relationship to the declared level of desirability. The conjunction analysis of desirable > indifferent revealed activity in the mid-cingulate cortex and in the anterior cingulate cortex. In the former, activity was greater for desirable and undesirable stimuli than for stimuli classed as indifferent. Other conjunction analyses produced no significant effects. These results show that categorizing any stimulus according to its desirability activates three different brain areas: the superior orbito-frontal, the mid-cingulate, and the anterior cingulate cortices. PMID:18728753

The Quartet does not play alone. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Marco-Pallarés, Josep; Mas-Herrero, Ernest

2015-06-01

The study of emotions has been an important topic in cognitive and affective neuroscience in the last decades. In the present manuscript, Koelsch et al. [1] propose a new neurobiological framework based on four emotional core systems (the Quartet), involved in different aspects of human emotion processing. This is an interesting theory that goes beyond classical emotion classification to describe the emotional experience based on four main cerebral components (brainstem, diencephalon, hippocampus, and orbitofrontal cortex). This approach allows the description of different classes of affects, including those that are unique in humans as emotional responses associated to abstract stimuli (for example, aesthetical stimuli such as art and music).

Affective neuroscience of self-generated thought.

PubMed

Fox, Kieran C R; Andrews-Hanna, Jessica R; Mills, Caitlin; Dixon, Matthew L; Markovic, Jelena; Thompson, Evan; Christoff, Kalina

2018-05-12

Despite increasing scientific interest in self-generated thought-mental content largely independent of the immediate environment-there has yet to be any comprehensive synthesis of the subjective experience and neural correlates of affect in these forms of thinking. Here, we aim to develop an integrated affective neuroscience encompassing many forms of self-generated thought-normal and pathological, moderate and excessive, in waking and in sleep. In synthesizing existing literature on this topic, we reveal consistent findings pertaining to the prevalence, valence, and variability of emotion in self-generated thought, and highlight how these factors might interact with self-generated thought to influence general well-being. We integrate these psychological findings with recent neuroimaging research, bringing attention to the neural correlates of affect in self-generated thought. We show that affect in self-generated thought is prevalent, positively biased, highly variable (both within and across individuals), and consistently recruits many brain areas implicated in emotional processing, including the orbitofrontal cortex, amygdala, insula, and medial prefrontal cortex. Many factors modulate these typical psychological and neural patterns, however; the emerging affective neuroscience of self-generated thought must endeavor to link brain function and subjective experience in both everyday self-generated thought as well as its dysfunctions in mental illness. © 2018 New York Academy of Sciences.

Corticosterone and decision-making in male Wistar rats: the effect of corticosterone application in the infralimbic and orbitofrontal cortex.

PubMed

Koot, Susanne; Koukou, Magdalini; Baars, Annemarie; Hesseling, Peter; van 't Klooster, José; Joëls, Marian; van den Bos, Ruud

2014-01-01

Corticosteroid hormones, released after stress, are known to influence neuronal activity and produce a wide range of effects upon the brain. They affect cognitive tasks including decision-making. Recently it was shown that systemic injections of corticosterone (CORT) disrupt reward-based decision-making in rats when tested in a rat model of the Iowa Gambling Task (rIGT), i.e., rats do not learn across trial blocks to avoid the long-term disadvantageous option. This effect was associated with a change in neuronal activity in prefrontal brain areas, i.e., the infralimbic (IL), lateral orbitofrontal (lOFC) and insular cortex, as assessed by changes in c-Fos expression. Here, we studied whether injections of CORT directly into the IL and lOFC lead to similar changes in decision-making. As in our earlier study, CORT was injected during the final 3 days of the behavioral paradigm, 25 min prior to behavioral testing. Infusions of vehicle into the IL led to a decreased number of visits to the disadvantageous arm across trial blocks, while infusion with CORT did not. Infusions into the lOFC did not lead to differences in the number of visits to the disadvantageous arm between vehicle treated and CORT treated rats. However, compared to vehicle treated rats of the IL group, performance of vehicle treated rats of the lOFC group was impaired, possibly due to cannulation/infusion-related damage of the lOFC affecting decision-making. Overall, these results show that infusions with CORT into the IL are sufficient to disrupt decision-making performance, pointing to a critical role of the IL in corticosteroid effects on reward-based decision-making. The data do not directly support that the same holds true for infusions into the lOFC.

Dopaminergic modulation of the orbitofrontal cortex affects attention, motivation and impulsive responding in rats performing the five-choice serial reaction time task.

PubMed

Winstanley, Catharine A; Zeeb, Fiona D; Bedard, Amanda; Fu, Kent; Lai, Barbara; Steele, Christina; Wong, Adeline C

2010-07-11

Understanding the neurobiological factors underlying individual differences in impulsivity may provide valuable insight into vulnerability to impulse control disorders. Recent data implicate both the orbitofrontal cortex (OFC) and the dopaminergic system in psychiatric disorders associated with high levels of impulsivity, including substance abuse, mania and obsessive-compulsive disorder. However, the consequences of modulating dopaminergic activity within the OFC on impulsive behaviour are largely unknown. The effects of direct intra-OFC infusions of agonists and antagonists at the dopamine D(1) and D(2) receptors were therefore assessed in rats performing the five-choice serial reaction time test (5CSRT) of attention and motor impulsivity. Intra-OFC administration of SCH23390, a D(1) receptor antagonist, decreased impulsive responding in highly impulsive (HI) rats, but did not affect behaviour in less impulsive (LI) animals. Furthermore, the D(2) agonist quinpirole caused significant deficits in task performance, impairing accuracy, increasing omissions and decreasing the number of trials completed, which resembled the effects of systemic administration. In contrast, the D(1) agonist SKF 81297 had little effect on behaviour. Neither agonist increased impulsivity. These data provide partial support for the suggestion that high levels of impulsivity are associated with increased dopamine levels within the OFC, but further indicate that simulating dopamine's actions selectively at the D(1) or D(2) receptor cannot reproduce a highly impulsive phenotype. Dopaminergic activity within the OFC may therefore modulate impulsivity indirectly, perhaps in conjunction with other neurotransmitter systems. Furthermore, D(2)-mediated neurotransmission within the OFC could make a more fundamental contribution to cognitive behaviour. Copyright 2010 Elsevier B.V. All rights reserved.

Orbitofrontal Reality Filtering

PubMed Central

Schnider, Armin

2013-01-01

Decades of research have deepened our understanding of how the brain forms memories and uses them to build our mental past and future. But how does it determine whether an evoked memory refers to the present and can be acted upon? The study of patients who confuse reality, as evident from confabulation and disorientation, has opened ways to explore this vital capacity. Results indicate that the brain recurs to a phylogenetically old faculty of the orbitofrontal cortex – extinction – and structures of the reward system to keep thought and behavior in phase with reality. PMID:23772208

Investigation of orbitofrontal sulcogyral pattern in chronic schizophrenia.

PubMed

Cropley, Vanessa L; Bartholomeusz, Cali F; Wu, Peter; Wood, Stephen J; Proffitt, Tina; Brewer, Warrick J; Desmond, Patricia M; Velakoulis, Dennis; Pantelis, Christos

2015-11-30

Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large sample of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Balkanizing the primate orbitofrontal cortex: Distinct subregions for comparing and contrasting values

PubMed Central

Rudebeck, Peter H.; Murray, Elisabeth A.

2014-01-01

The primate orbitofrontal cortex (OFC) is often treated as a single entity, but architectonic and connectional neuroanatomy indicates that it has distinguishable parts. Nevertheless, few studies have attempted to dissociate the functions of its subregions. Here we review findings from recent neuropsychological and neurophysiological studies that do so. The lateral OFC seems to be important for learning, representing and updating specific object–reward associations. Medial OFC seems to be important for value comparisons and choosing among objects on that basis. Rather than viewing this dissociation of function in terms of learning versus choosing, however, we suggest that it reflects the distinction between contrasts and comparisons: differences versus similarities. Making use of high-dimensional representations that arise from the convergence of several sensory modalities, the lateral OFC encodes contrasts among outcomes. The medial MFC reduces these contrasting representations of value to a single dimension, a common currency, in order to compare alternative choices. PMID:22145870

Elucidating the underlying components of food valuation in the human orbitofrontal cortex.

PubMed

Suzuki, Shinsuke; Cross, Logan; O'Doherty, John P

2017-12-01

The valuation of food is a fundamental component of our decision-making. Yet little is known about how value signals for food and other rewards are constructed by the brain. Using a food-based decision task in human participants, we found that subjective values can be predicted from beliefs about constituent nutritive attributes of food: protein, fat, carbohydrates and vitamin content. Multivariate analyses of functional MRI data demonstrated that, while food value is represented in patterns of neural activity in both medial and lateral parts of the orbitofrontal cortex (OFC), only the lateral OFC represents the elemental nutritive attributes. Effective connectivity analyses further indicate that information about the nutritive attributes represented in the lateral OFC is integrated within the medial OFC to compute an overall value. These findings provide a mechanistic account for the construction of food value from its constituent nutrients.

A functional difference in information processing between orbitofrontal cortex and ventral striatum during decision-making behaviour.

PubMed

Stott, Jeffrey J; Redish, A David

2014-11-05

Both orbitofrontal cortex (OFC) and ventral striatum (vStr) have been identified as key structures that represent information about value in decision-making tasks. However, the dynamics of how this information is processed are not yet understood. We recorded ensembles of cells from OFC and vStr in rats engaged in the spatial adjusting delay-discounting task, a decision-making task that involves a trade-off between delay to and magnitude of reward. Ventral striatal neural activity signalled information about reward before the rat's decision, whereas such reward-related signals were absent in OFC until after the animal had committed to its decision. These data support models in which vStr is directly involved in action selection, but OFC processes decision-related information afterwards that can be used to compare the predicted and actual consequences of behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Regional gray matter reduction and theory of mind deficit in the early phase of schizophrenia: a voxel-based morphometric study.

PubMed

Herold, R; Feldmann, A; Simon, M; Tényi, T; Kövér, F; Nagy, F; Varga, E; Fekete, S

2009-03-01

We tested the association between theory of mind (ToM) performance and structural changes in the brains of patients in the early course of schizophrenia. Voxel-based morphometry (VBM) data of 18 patients with schizophrenia were compared with those of 21 controls. ToM skills were assessed by computerized faux pas (FP) tasks. Patients with schizophrenia performed significantly worse in FP tasks than healthy subjects. VBM revealed significantly reduced gray matter density in certain frontal, temporal and subcortical regions in patients with schizophrenia. Poor FP performance of schizophrenics correlated with gray matter reduction in the left orbitofrontal cortex and right temporal pole. Our data indicate an association between poor ToM performance and regional gray matter reduction in the left orbitofrontal cortex and right temporal pole shortly after the onset of schizophrenia.

Right Orbitofrontal Cortex Mediates Conscious Olfactory Perception

PubMed Central

Li, Wen; Lopez, Leonardo; Osher, Jason; Howard, James D.; Parrish, Todd B.; Gottfried, Jay A.

2013-01-01

Understanding how the human brain translates sensory impressions into conscious percepts is a key challenge of neuroscience research. Work in this area has overwhelmingly centered on the conscious experience of vision at the exclusion of the other senses—in particular, smell. We hypothesized that the orbitofrontal cortex (OFC) is a central substrate for olfactory conscious experience because of its privileged physiological role in odor processing. Combining functional magnetic resonance imaging, peripheral autonomic recordings, and olfactory psychophysics, we studied a case of complete anosmia (smell loss) in a patient with circumscribed traumatic brain injury to the right OFC. Despite a complete absence of conscious olfaction, the patient exhibited robust “blind smell,” as indexed by reliable odor-evoked neural activity in the left OFC and normal autonomic responses to odor hedonics during presentation of stimuli to the left nostril. These data highlight the right OFC’s critical role in subserving human olfactory consciousness. PMID:20817780

Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

PubMed

Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

2017-01-01

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Orbitofrontal cortex mediates pain inhibition by monetary reward.

PubMed

Becker, Susanne; Gandhi, Wiebke; Pomares, Florence; Wager, Tor D; Schweinhardt, Petra

2017-04-01

Pleasurable stimuli, including reward, inhibit pain, but the level of the neuraxis at which they do so and the cerebral processes involved are unknown. Here, we characterized a brain circuitry mediating pain inhibition by reward. Twenty-four healthy participants underwent functional magnetic resonance imaging while playing a wheel of fortune game with simultaneous thermal pain stimuli and monetary wins or losses. As expected, winning decreased pain perception compared to losing. Inter-individual differences in pain modulation by monetary wins relative to losses correlated with activation in the medial orbitofrontal cortex (mOFC). When pain and reward occured simultaneously, mOFCs functional connectivity changed: the signal time course in the mOFC condition-dependent correlated negatively with the signal time courses in the rostral anterior insula, anterior-dorsal cingulate cortex and primary somatosensory cortex, which might signify moment-to-moment down-regulation of these regions by the mOFC. Monetary wins and losses did not change the magnitude of pain-related activation, including in regions that code perceived pain intensity when nociceptive input varies and/or receive direct nociceptive input. Pain inhibition by reward appears to involve brain regions not typically involved in nociceptive intensity coding but likely mediate changes in the significance and/or value of pain. © The Author (2017). Published by Oxford University Press.

Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

PubMed Central

Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

2015-01-01

Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.

PubMed

Ghashghaei, H T; Hilgetag, C C; Barbas, H

2007-02-01

The prefrontal cortex and the amygdala have synergistic roles in regulating purposive behavior, effected through bidirectional pathways. Here we investigated the largely unknown extent and laminar relationship of prefrontal input-output zones linked with the amygdala using neural tracers injected in the amygdala in rhesus monkeys. Prefrontal areas varied vastly in their connections with the amygdala, with the densest connections found in posterior orbitofrontal and posterior medial cortices, and the sparsest in anterior lateral prefrontal areas, especially area 10. Prefrontal projection neurons directed to the amygdala originated in layer 5, but significant numbers were also found in layers 2 and 3 in posterior medial and orbitofrontal cortices. Amygdalar axonal terminations in prefrontal cortex were most frequently distributed in bilaminar bands in the superficial and deep layers, by columns spanning the entire cortical depth, and less frequently as small patches centered in the superficial or deep layers. Heavy terminations in layers 1-2 overlapped with calbindin-positive inhibitory neurons. A comparison of the relationship of input to output projections revealed that among the most heavily connected cortices, cingulate areas 25 and 24 issued comparatively more projections to the amygdala than they received, whereas caudal orbitofrontal areas were more receivers than senders. Further, there was a significant relationship between the proportion of 'feedforward' cortical projections from layers 2-3 to 'feedback' terminations innervating the superficial layers of prefrontal cortices. These findings indicate that the connections between prefrontal cortices and the amygdala follow similar patterns as corticocortical connections, and by analogy suggest pathways underlying the sequence of information processing for emotions.

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards

PubMed Central

Burke, Kathryn A.; Franz, Theresa M.; Miller, Danielle N.; Schoenbaum, Geoffrey

2009-01-01

Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald’s Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways1, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction2,3. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making4, was critical for the former but not for the latter form of conditioned reinforcement. PMID:18563088

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards.

PubMed

Burke, Kathryn A; Franz, Theresa M; Miller, Danielle N; Schoenbaum, Geoffrey

2008-07-17

Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for the latter form of conditioned reinforcement.

Reduced recruitment of orbitofrontal cortex to human social chemosensory cues in social anxiety.

PubMed

Zhou, Wen; Hou, Ping; Zhou, Yuxiang; Chen, Denise

2011-04-01

Social anxiety refers to the prevalent and debilitating experience of fear and anxiety of being scrutinized in social situations. It originates from both learned (e.g. adverse social conditioning) and innate (e.g. shyness) factors. Research on social anxiety has traditionally focused on negative emotions induced by visual and auditory social cues in socially anxious clinical populations, and posits a dysfunctional orbitofrontal-amygdala circuit as a primary etiological mechanism. Yet as a trait, social anxiety is independent of one's specific emotional state. Here we probe the neural substrate of intrinsic social anxiety by employing a unique type of social stimuli, airborne human social chemosensory cues that are inherently social, ubiquitously present, and yet operating below verbal awareness. We show that the adopted social chemosensory cues were not perceived to be human-related, did not differentially bias self-report of anxiety or autonomic nervous system responses, yet individuals with elevated social anxiety demonstrated a reduced recruitment of the orbitofrontal cortex to social chemosensory cues. No reciprocal activity in the amygdala was observed. Our findings point to an intrinsic neural substrate underlying social anxiety that is not associated with prior adverse social conditioning, thereby providing the first neural evidence for the inherent social aspect of this enigmatic phenomenon. Copyright © 2010 Elsevier Inc. All rights reserved.

Olfactory memory and maternal behaviour-induced changes in c-fos and zif/268 mRNA expression in the sheep brain.

PubMed

Da Costa, A P; Broad, K D; Kendrick, K M

1997-06-01

In sheep maternal behaviour and the formation of the selective olfactory, ewe/lamb bond are induced by feedback to the brain from stimulation of the vagina and cervix during parturition. In the present study, we have used in situ hybridization histochemistry to quantify changes in cellular expression of two immediately-early genes, c-fos and zif/268, in order to identify activated brain regions during the induction of maternal behaviour and olfactory bonding as well as regions where plastic changes are occurring during with the formation of the olfactory memory associated with bonding. Three different treatment groups were used. One group gave birth normally, became maternal and were allowed to interact with their lambs for 30 min. A second group received exogenous treatment with oestradiol and progesterone to induce lactation and then received a 5-min period of artificial stimulation of the vagina and cervix (VCS) which reliably induces maternal behaviour but could not interact with lambs. A final control group received exogenous hormone treatment but no VCS or interaction with lambs. Compared to the control group, post-partum animals and animals that had received VCS showed increased c-fos expression in a number of cortical regions (cingulate, entorhinal and somatosensory), the mediodorsal thalamic nucleus and the lateral habenula, the limbic system (bed nucleus of the stria terminalis, lateral septum, medial arnygdala, dentate gyrus and the CA3 region of the hippocampus) and the hypothalamus (medial preoptic area, mediobasal hypothalamus, paraventricular nucleus, supraoptic nucleus and periventricular complex). The group that gave birth and had contact with their lambs for 30 min had significantly enhanced c-fos mRNA expression in the cingulate cortex compared to those receiving VCS and additionally showed significantly increased c-fos mRNA expression in olfactory processing regions (olfactory bulb, piriform cortex and orbitofrontal cortex). Expression of zif/268 was significantly increased in the entorhinal cortex, orbitofrontal cortex and dentate gyrus of the parturition group compared to either the control or the VCS alone groups. These results show a clear differentiation between neural substrates controlling the expression of maternal behaviour and those involved in the olfactory memory process associated with selective recognition of offspring although at the level of the hippocampus and cingulate cortex there may be some degree of overlap. Alterations in zif/268 at tertiary processing sites for olfactory information (orbitofrontal cortex) and the entorhinal cortex and dentate gyrus may reflect plastic changes occurring during the early stages of olfactory memory formation.

Cocaine cue-induced dopamine release in the human prefrontal cortex.

PubMed

Milella, Michele S; Fotros, Aryandokht; Gravel, Paul; Casey, Kevin F; Larcher, Kevin; Verhaeghe, Jeroen A J; Cox, Sylvia M L; Reader, Andrew J; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

2016-08-01

Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.

Underconnectivity between voice-selective cortex and reward circuitry in children with autism.

PubMed

Abrams, Daniel A; Lynch, Charles J; Cheng, Katherine M; Phillips, Jennifer; Supekar, Kaustubh; Ryali, Srikanth; Uddin, Lucina Q; Menon, Vinod

2013-07-16

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume.

PubMed

Dalwani, Manish S; McMahon, Mary Agnes; Mikulich-Gilbertson, Susan K; Young, Susan E; Regner, Michael F; Raymond, Kristen M; McWilliams, Shannon K; Banich, Marie T; Tanabe, Jody L; Crowley, Thomas J; Sakai, Joseph T

2015-01-01

Structural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum). We conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold. Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls. Female adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.

The insula is not specifically involved in disgust processing: an fMRI study.

PubMed

Schienle, A; Stark, R; Walter, B; Blecker, C; Ott, U; Kirsch, P; Sammer, G; Vaitl, D

2002-11-15

fMRI studies have shown that the perception of facial disgust expressions specifically activates the insula. The present fMRI study investigated whether this structure is also involved in the processing of visual stimuli depicting non-mimic disgust elicitors compared to fear-inducing and neutral scenes. Twelve female subjects were scanned while viewing alternating blocks of 40 disgust-inducing, 40 fear-inducing and 40 affectively neutral pictures, shown for 1.5 s each. Afterwards, affective ratings were assessed. The disgust pictures, rated as highly repulsive, induced activation in the insula, the amygdala, the orbitofrontal and occipito-temporal cortex. Since during the fear condition the insula was also involved, our findings do not fit the idea of the insula as a specific disgust processor.

Identity-Specific Reward Representations in Orbitofrontal Cortex Are Modulated by Selective Devaluation

PubMed Central

Howard, James D.

2017-01-01

Goal-directed behavior is sensitive to the current value of expected outcomes. This requires independent representations of specific rewards, which have been linked to orbitofrontal cortex (OFC) function. However, the mechanisms by which the human brain updates specific goals on the fly, and translates those updates into choices, have remained unknown. Here we implemented selective devaluation of appetizing food odors in combination with pattern-based neuroimaging and a decision-making task. We found that in a hungry state, participants chose to smell high-intensity versions of two value-matched food odor rewards. After eating a meal corresponding to one of the two odors, participants switched choices toward the low intensity of the sated odor but continued to choose the high intensity of the nonsated odor. This sensory-specific behavioral effect was mirrored by pattern-based changes in fMRI signal in lateral posterior OFC, where specific reward identity representations were altered after the meal for the sated food odor but retained for the nonsated counterpart. In addition, changes in functional connectivity between the OFC and general value coding in ventromedial prefrontal cortex (vmPFC) predicted individual differences in satiety-related choice behavior. These findings demonstrate how flexible representations of specific rewards in the OFC are updated by devaluation, and how functional connections to vmPFC reflect the current value of outcomes and guide goal-directed behavior. SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) is critical for goal-directed behavior. A recent proposal is that OFC fulfills this function by representing a variety of state and task variables (“cognitive maps”), including a conjunction of expected reward identity and value. Here we tested how identity-specific representations of food odor reward are updated by satiety. We found that fMRI pattern-based signatures of reward identity in lateral posterior OFC were modulated after selective devaluation, and that connectivity between this region and general value coding ventromedial prefrontal cortex (vmPFC) predicted choice behavior. These results provide evidence for a mechanism by which devaluation modulates a cognitive map of expected reward in OFC and thereby alters general value signals in vmPFC to guide goal-directed behavior. PMID:28159906

Cascade of neural processing orchestrates cognitive control in human frontal cortex

PubMed Central

Tang, Hanlin; Yu, Hsiang-Yu; Chou, Chien-Chen; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2016-01-01

Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001 PMID:26888070

Adverse Effects of Cannabis on Adolescent Brain Development: A Longitudinal Study

PubMed Central

Camchong, Jazmin; Lim, Kelvin O; Kumra, Sanjiv

2017-01-01

Abstract Cannabis is widely perceived as a safe recreational drug and its use is increasing in youth. It is important to understand the implications of cannabis use during childhood and adolescence on brain development. This is the first longitudinal study that compared resting functional connectivity of frontally mediated networks between 43 healthy controls (HCs; 20 females; age M = 16.5 ± 2.7) and 22 treatment-seeking adolescents with cannabis use disorder (CUD; 8 females; age M = 17.6 ± 2.4). Increases in resting functional connectivity between caudal anterior cingulate cortex (ACC) and superior frontal gyrus across time were found in HC, but not in CUD. CUD showed a decrease in functional connectivity between caudal ACC and dorsolateral and orbitofrontal cortices across time. Lower functional connectivity between caudal ACC cortex and orbitofrontal cortex at baseline predicted higher amounts of cannabis use during the following 18 months. Finally, high amounts of cannabis use during the 18-month interval predicted lower intelligence quotient and slower cognitive function measured at follow-up. These data provide compelling longitudinal evidence suggesting that repeated exposure to cannabis during adolescence may have detrimental effects on brain resting functional connectivity, intelligence, and cognitive function. PMID:26912785

Left Posterior Orbitofrontal Cortex Is Associated With Odor-Induced Autobiographical Memory: An fMRI Study.

PubMed

Watanabe, Keiko; Masaoka, Yuri; Kawamura, Mitsuru; Yoshida, Masaki; Koiwa, Nobuyoshi; Yoshikawa, Akira; Kubota, Satomi; Ida, Masahiro; Ono, Kenjiro; Izumizaki, Masahiko

2018-01-01

Autobiographical odor memory (AM-odor) accompanied by a sense of realism of a specific memory elicits strong emotions. AM-odor differs from memory triggered by other sensory modalities, possibly because olfaction involves a unique sensory process. Here, we examined the orbitofrontal cortex (OFC), using functional magnetic resonance imaging (fMRI) to determine which OFC subregions are related to AM-odor. Both AM-odor and a control odor successively increased subjective ratings of comfortableness and pleasantness. Importantly, AM-odor also increased arousal levels and the vividness of memories, and was associated with a deep and slow breathing pattern. fMRI analysis indicated robust activation in the left posterior OFC (L-POFC). Connectivity between the POFC and whole brain regions was estimated using psychophysiological interaction analysis (PPI). We detected several trends in connectivity between L-POFC and bilateral precuneus, bilateral rostral dorsal anterior cingulate cortex (rdACC), and left parahippocampus, which will be useful for targeting our hypotheses for future investigations. The slow breathing observed in AM-odor was correlated with rdACC activation. Odor associated with emotionally significant autobiographical memories was accompanied by slow and deep breathing, possibly involving rdACC processing.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity.

PubMed

Contreras-Rodríguez, Oren; Albein-Urios, Natalia; Vilar-López, Raquel; Perales, Jose C; Martínez-Gonzalez, Jose M; Fernández-Serrano, Maria J; Lozano-Rojas, Oscar; Clark, Luke; Verdejo-García, Antonio

2016-05-01

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect. © 2015 Society for the Study of Addiction.

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

PubMed Central

Márquez, C; Poirier, G L; Cordero, M I; Larsen, M H; Groner, A; Marquis, J; Magistretti, P J; Trono, D; Sandi, C

2013-01-01

Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress with face, construct and predictive validity. We show that male rats submitted to fear-induction experiences during the peripubertal period exhibit high and sustained rates of increased aggression at adulthood, even against unthreatening individuals, and increased testosterone/corticosterone ratio. They also exhibit hyperactivity in the amygdala under both basal conditions (evaluated by 2-deoxy-glucose autoradiography) and after a resident–intruder (RI) test (evaluated by c-Fos immunohistochemistry), and hypoactivation of the medial orbitofrontal (MO) cortex after the social challenge. Alterations in the connectivity between the orbitofrontal cortex and the amygdala were linked to the aggressive phenotype. Increased and sustained expression levels of the monoamine oxidase A (MAOA) gene were found in the prefrontal cortex but not in the amygdala of peripubertally stressed animals. They were accompanied by increased activatory acetylation of histone H3, but not H4, at the promoter of the MAOA gene. Treatment with an MAOA inhibitor during adulthood reversed the peripuberty stress-induced antisocial behaviors. Beyond the characterization and validation of the model, we present novel data highlighting changes in the serotonergic system in the prefrontal cortex—and pointing at epigenetic control of the MAOA gene—in the establishment of the link between peripubertal stress and later pathological aggression. Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence of violent behaviors. PMID:23321813

Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Hamazaki, Tomohito; Inadera, Hidekuni

2013-11-30

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reduced Cortical Thickness and Increased Surface Area in Antisocial Personality Disorder

PubMed Central

Jiang, Weixiong; Li, Gang; Liu, Huasheng; Shi, Feng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2016-01-01

Antisocial Personality Disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness and surface area, as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of cortical thickness and surface area in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger surface area in several specific brain regions, i.e., bilateral superior frontal gyrus, orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus, middle temporal gyrus, and left bank of superior temporal sulcus. In addition, we also found that the ability of impulse control was positively correlated with cortical thickness in the superior frontal gyrus, middle frontal gyrus, orbitofrontal cortex, pars triangularis, superior temporal gyrus, and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in cortical thickness and surface area in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD. PMID:27600947

Age Differences in Prefrontal Surface Area and Thickness in Middle Aged to Older Adults.

PubMed

Dotson, Vonetta M; Szymkowicz, Sarah M; Sozda, Christopher N; Kirton, Joshua W; Green, Mackenzie L; O'Shea, Andrew; McLaren, Molly E; Anton, Stephen D; Manini, Todd M; Woods, Adam J

2015-01-01

Age is associated with reductions in surface area and cortical thickness, particularly in prefrontal regions. There is also evidence of greater thickness in some regions at older ages. Non-linear age effects in some studies suggest that age may continue to impact brain structure in later decades of life, but relatively few studies have examined the impact of age on brain structure within middle-aged to older adults. We investigated age differences in prefrontal surface area and cortical thickness in healthy adults between the ages of 51 and 81 years. Participants received a structural 3-Tesla magnetic resonance imaging scan. Based on a priori hypotheses, primary analyses focused on surface area and cortical thickness in the dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex. We also performed exploratory vertex-wise analyses of surface area and cortical thickness across the entire cortex. We found that older age was associated with smaller surface area in the dorsolateral prefrontal and orbitofrontal cortices but greater cortical thickness in the dorsolateral prefrontal and anterior cingulate cortices. Vertex-wise analyses revealed smaller surface area in primarily frontal regions at older ages, but no age effects were found for cortical thickness. Results suggest age is associated with reduced surface area but greater cortical thickness in prefrontal regions during later decades of life, and highlight the differential effects age has on regional surface area and cortical thickness.

Reduced cortical thickness and increased surface area in antisocial personality disorder.

PubMed

Jiang, Weixiong; Li, Gang; Liu, Huasheng; Shi, Feng; Wang, Tao; Shen, Celina; Shen, Hui; Lee, Seong-Whan; Hu, Dewen; Wang, Wei; Shen, Dinggang

2016-11-19

Antisocial personality disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness (CTh) and surface area (SA), as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of CTh and SA in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger SA in several specific brain regions, i.e., bilateral superior frontal gyrus (SFG), orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus (MFG), middle temporal gyrus (MTG), and left bank of superior temporal sulcus (STS). In addition, we also found that the ability of impulse control was positively correlated with CTh in the SFG, MFG, orbitofrontal cortex (OFC), pars triangularis, superior temporal gyrus (STG), and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in CTh and SA in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neural evidence that human emotions share core affective properties.

PubMed

Wilson-Mendenhall, Christine D; Barrett, Lisa Feldman; Barsalou, Lawrence W

2013-06-01

Research on the "emotional brain" remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect--a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.

Neural Evidence that Human Emotions Share Core Affective Properties

PubMed Central

Wilson-Mendenhall, Christine D.; Barrett, Lisa Feldman; Barsalou, Lawrence W.

2014-01-01

Research on the “emotional brain” remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect – a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena. PMID:23603916

Neural mechanisms underlying the effects of face-based affective signals on memory for faces: a tentative model

PubMed Central

Tsukiura, Takashi

2012-01-01

In our daily lives, we form some impressions of other people. Although those impressions are affected by many factors, face-based affective signals such as facial expression, facial attractiveness, or trustworthiness are important. Previous psychological studies have demonstrated the impact of facial impressions on remembering other people, but little is known about the neural mechanisms underlying this psychological process. The purpose of this article is to review recent functional MRI (fMRI) studies to investigate the effects of face-based affective signals including facial expression, facial attractiveness, and trustworthiness on memory for faces, and to propose a tentative concept for understanding this affective-cognitive interaction. On the basis of the aforementioned research, three brain regions are potentially involved in the processing of face-based affective signals. The first candidate is the amygdala, where activity is generally modulated by both affectively positive and negative signals from faces. Activity in the orbitofrontal cortex (OFC), as the second candidate, increases as a function of perceived positive signals from faces; whereas activity in the insular cortex, as the third candidate, reflects a function of face-based negative signals. In addition, neuroscientific studies have reported that the three regions are functionally connected to the memory-related hippocampal regions. These findings suggest that the effects of face-based affective signals on memory for faces could be modulated by interactions between the regions associated with the processing of face-based affective signals and the hippocampus as a memory-related region. PMID:22837740

Covert shift of attention modulates the value encoding in the orbitofrontal cortex

PubMed Central

Xie, Yang; Nie, Chechang

2018-01-01

During value-based decision making, we often evaluate the value of each option sequentially by shifting our attention, even when the options are presented simultaneously. The orbitofrontal cortex (OFC) has been suggested to encode value during value-based decision making. Yet it is not known how its activity is modulated by attention shifts. We investigated this question by employing a passive viewing task that allowed us to disentangle effects of attention, value, choice and eye movement. We found that the attention modulated OFC activity through a winner-take-all mechanism. When we attracted the monkeys’ attention covertly, the OFC neuronal activity reflected the reward value of the newly attended cue. The shift of attention could be explained by a normalization model. Our results strongly argue for the hypothesis that the OFC neuronal activity represents the value of the attended item. They provide important insights toward understanding the OFC’s role in value-based decision making. PMID:29533184

Covert shift of attention modulates the value encoding in the orbitofrontal cortex.

PubMed

Xie, Yang; Nie, Chechang; Yang, Tianming

2018-03-13

During value-based decision making, we often evaluate the value of each option sequentially by shifting our attention, even when the options are presented simultaneously. The orbitofrontal cortex (OFC) has been suggested to encode value during value-based decision making. Yet it is not known how its activity is modulated by attention shifts. We investigated this question by employing a passive viewing task that allowed us to disentangle effects of attention, value, choice and eye movement. We found that the attention modulated OFC activity through a winner-take-all mechanism. When we attracted the monkeys' attention covertly, the OFC neuronal activity reflected the reward value of the newly attended cue. The shift of attention could be explained by a normalization model. Our results strongly argue for the hypothesis that the OFC neuronal activity represents the value of the attended item. They provide important insights toward understanding the OFC's role in value-based decision making. © 2018, Xie et al.

The value of identity: olfactory notes on orbitofrontal cortex function.

PubMed

Gottfried, Jay A; Zelano, Christina

2011-12-01

Neuroscientific research has emphatically promoted the idea that the key function of the orbitofrontal cortex (OFC) is to encode value. Associative learning studies indicate that OFC representations of stimulus cues reflect the predictive value of expected outcomes. Neuroeconomic studies suggest that the OFC distills abstract representations of value from discrete commodities to optimize choice. Although value-based models provide good explanatory power for many different findings, these models are typically disconnected from the very stimuli and commodities giving rise to those value representations. Little provision is made, either theoretically or empirically, for the necessary cooperative role of object identity, without which value becomes orphaned from its source. As a step toward remediating the value of identity, this review provides a focused olfactory survey of OFC research, including new work from our lab, to highlight the elemental involvement of this region in stimulus-specific predictive coding of both perceptual outcomes and expected values. © 2011 New York Academy of Sciences.

Instructed knowledge shapes feedback-driven aversive learning in striatum and orbitofrontal cortex, but not the amygdala

PubMed Central

Atlas, Lauren Y; Doll, Bradley B; Li, Jian; Daw, Nathaniel D; Phelps, Elizabeth A

2016-01-01

Socially-conveyed rules and instructions strongly shape expectations and emotions. Yet most neuroscientific studies of learning consider reinforcement history alone, irrespective of knowledge acquired through other means. We examined fear conditioning and reversal in humans to test whether instructed knowledge modulates the neural mechanisms of feedback-driven learning. One group was informed about contingencies and reversals. A second group learned only from reinforcement. We combined quantitative models with functional magnetic resonance imaging and found that instructions induced dissociations in the neural systems of aversive learning. Responses in striatum and orbitofrontal cortex updated with instructions and correlated with prefrontal responses to instructions. Amygdala responses were influenced by reinforcement similarly in both groups and did not update with instructions. Results extend work on instructed reward learning and reveal novel dissociations that have not been observed with punishments or rewards. Findings support theories of specialized threat-detection and may have implications for fear maintenance in anxiety. DOI: http://dx.doi.org/10.7554/eLife.15192.001 PMID:27171199

Lucky Rhythms in Orbitofrontal Cortex Bias Gambling Decisions in Humans

PubMed Central

Sacré, Pierre; Kerr, Matthew S. D.; Kahn, Kevin; Gonzalez-Martinez, Jorge; Bulacio, Juan; Park, Hyun-Joo; Johnson, Matthew A.; Thompson, Susan; Jones, Jaes; Chib, Vikram S.; Gale, John T.; Sarma, Sridevi V.

2016-01-01

It is well established that emotions influence our decisions, yet the neural basis of this biasing effect is not well understood. Here we directly recorded local field potentials from the OrbitoFrontal Cortex (OFC) in five human subjects performing a financial decision-making task. We observed a striking increase in gamma-band (36–50 Hz) oscillatory activity that reflected subjects’ decisions to make riskier choices. Additionally, these gamma rhythms were linked back to mismatched expectations or “luck” occurring in past trials. Specifically, when a subject expected to win but lost, the trial was defined as “unlucky” and when the subject expected to lose but won, the trial was defined as “lucky”. Finally, a fading memory model of luck correlated to an objective measure of emotion, heart rate variability. Our findings suggest OFC may play a pivotal role in processing a subject’s internal (emotional) state during financial decision-making, a particularly interesting result in light of the more recent “cognitive map” theory of OFC function. PMID:27830753

High-Throughput Analysis of Age-Dependent Protein Changes in Layer II/III of the Human Orbitofrontal Cortex

NASA Astrophysics Data System (ADS)

Kapadia, Fenika

Studies on the orbitofrontal cortex (OFC) during normal aging have shown a decline in cognitive functions, a loss of spines/synapses in layer III and gene expression changes related to neural communication. Biological changes during the course of normal aging are summarized into 9 hallmarks based on aging in peripheral tissue. Whether these hallmarks apply to non-dividing brain tissue is not known. Therefore, we opted to perform large-scale proteomic profiling of the OFC layer II/III during normal aging from 15 young and 18 old male subjects. MaxQuant was utilized for label-free quantification and statistical analysis by the Random Intercept Model (RIM) identified 118 differentially expressed (DE) age-related proteins. Altered neural communication was the most represented hallmark of aging (54% of DE proteins), highlighting the importance of communication in the brain. Functional analysis showed enrichment in GABA/glutamate signaling and pro-inflammatory responses. The former may contribute to alterations in excitation/inhibition, leading to cognitive decline during aging.

Human Orbitofrontal Cortex Represents a Cognitive Map of State Space.

PubMed

Schuck, Nicolas W; Cai, Ming Bo; Wilson, Robert C; Niv, Yael

2016-09-21

Although the orbitofrontal cortex (OFC) has been studied intensely for decades, its precise functions have remained elusive. We recently hypothesized that the OFC contains a "cognitive map" of task space in which the current state of the task is represented, and this representation is especially critical for behavior when states are unobservable from sensory input. To test this idea, we apply pattern-classification techniques to neuroimaging data from humans performing a decision-making task with 16 states. We show that unobservable task states can be decoded from activity in OFC, and decoding accuracy is related to task performance and the occurrence of individual behavioral errors. Moreover, similarity between the neural representations of consecutive states correlates with behavioral accuracy in corresponding state transitions. These results support the idea that OFC represents a cognitive map of task space and establish the feasibility of decoding state representations in humans using non-invasive neuroimaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Complementary contributions of basolateral amygdala and orbitofrontal cortex to value learning under uncertainty

PubMed Central

Stolyarova, Alexandra; Izquierdo, Alicia

2017-01-01

We make choices based on the values of expected outcomes, informed by previous experience in similar settings. When the outcomes of our decisions consistently violate expectations, new learning is needed to maximize rewards. Yet not every surprising event indicates a meaningful change in the environment. Even when conditions are stable overall, outcomes of a single experience can still be unpredictable due to small fluctuations (i.e., expected uncertainty) in reward or costs. In the present work, we investigate causal contributions of the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) in rats to learning under expected outcome uncertainty in a novel delay-based task that incorporates both predictable fluctuations and directional shifts in outcome values. We demonstrate that OFC is required to accurately represent the distribution of wait times to stabilize choice preferences despite trial-by-trial fluctuations in outcomes, whereas BLA is necessary for the facilitation of learning in response to surprising events. DOI: http://dx.doi.org/10.7554/eLife.27483.001 PMID:28682238

Distinct Roles for the Amygdala and Orbitofrontal Cortex in Representing the Relative Amount of Expected Reward.

PubMed

Saez, Rebecca A; Saez, Alexandre; Paton, Joseph J; Lau, Brian; Salzman, C Daniel

2017-07-05

The same reward can possess different motivational meaning depending upon its magnitude relative to other rewards. To study the neurophysiological mechanisms mediating assignment of motivational meaning, we recorded the activity of neurons in the amygdala and orbitofrontal cortex (OFC) of monkeys during a Pavlovian task in which the relative amount of liquid reward associated with one conditioned stimulus (CS) was manipulated by changing the reward amount associated with a second CS. Anticipatory licking tracked relative reward magnitude, implying that monkeys integrated information about recent rewards to adjust the motivational meaning of a CS. Upon changes in relative reward magnitude, neural responses to reward-predictive cues updated more rapidly in OFC than amygdala, and activity in OFC but not the amygdala was modulated by recent reward history. These results highlight a distinction between the amygdala and OFC in assessing reward history to support the flexible assignment of motivational meaning to sensory cues. Copyright © 2017 Elsevier Inc. All rights reserved.

Effective connectivities of cortical regions for top-down face processing: A Dynamic Causal Modeling study

PubMed Central

Li, Jun; Liu, Jiangang; Liang, Jimin; Zhang, Hongchuan; Zhao, Jizheng; Rieth, Cory A.; Huber, David E.; Li, Wu; Shi, Guangming; Ai, Lin; Tian, Jie; Lee, Kang

2013-01-01

To study top-down face processing, the present study used an experimental paradigm in which participants detected non-existent faces in pure noise images. Conventional BOLD signal analysis identified three regions involved in this illusory face detection. These regions included the left orbitofrontal cortex (OFC) in addition to the right fusiform face area (FFA) and right occipital face area (OFA), both of which were previously known to be involved in both top-down and bottom-up processing of faces. We used Dynamic Causal Modeling (DCM) and Bayesian model selection to further analyze the data, revealing both intrinsic and modulatory effective connectivities among these three cortical regions. Specifically, our results support the claim that the orbitofrontal cortex plays a crucial role in the top-down processing of faces by regulating the activities of the occipital face area, and the occipital face area in turn detects the illusory face features in the visual stimuli and then provides this information to the fusiform face area for further analysis. PMID:20423709

Orbitofrontal cortex and basolateral amygdala lesions result in suboptimal and dissociable reward choices on cue-guided effort in rats

PubMed Central

Ostrander, Serena; Cazares, Victor A.; Kim, Charissa; Cheung, Shauna; Gonzalez, Isabel; Izquierdo, Alicia

2011-01-01

The orbitofrontal cortex (OFC) and basolateral nucleus of the amygdala (BLA) are important neural regions in responding adaptively to changes in the incentive value of reward. Recent evidence suggests these structures may be differentially engaged in effort and cue-guided choice behavior. In two t-maze experiments, we examined the effects of bilateral lesions of either BLA or OFC on 1) effortful choices where rats could climb a barrier for a high reward or select a low reward with no effort and 2) effortful choices when a visual cue signaled changes in reward magnitude. In both experiments, BLA rats displayed transient work aversion, choosing the effortless low reward option. OFC rats were work averse only in the no cue conditions, displaying a pattern of attenuated recovery from the cue conditions signaling reward unavailability in the effortful arm. Control measures rule out an inability to discriminate the cue in either lesion group. PMID:21639604

Effects of loss aversion on neural responses to loss outcomes: An event-related potential study.

PubMed

Kokmotou, Katerina; Cook, Stephanie; Xie, Yuxin; Wright, Hazel; Soto, Vicente; Fallon, Nicholas; Giesbrecht, Timo; Pantelous, Athanasios; Stancak, Andrej

2017-05-01

Loss aversion is the tendency to prefer avoiding losses over acquiring gains of the same amount. To shed light on the spatio-temporal processes underlying loss aversion, we analysed the associations between individual loss aversion and electrophysiological responses to loss and gain outcomes in a monetary gamble task. Electroencephalographic feedback-related negativity (FRN) was computed in 29 healthy participants as the difference in electrical potentials between losses and gains. Loss aversion was evaluated using non-linear parametric fitting of choices in a separate gamble task. Loss aversion correlated positively with FRN amplitude (233-263ms) at electrodes covering the lower face. Feedback related potentials were modelled by five equivalent source dipoles. From these dipoles, stronger activity in a source located in the orbitofrontal cortex was associated with loss aversion. The results suggest that loss aversion implemented during risky decision making is related to a valuation process in the orbitofrontal cortex, which manifests during learning choice outcomes. Copyright © 2017. Published by Elsevier B.V.

Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values.

PubMed

Rudebeck, Peter H; Murray, Elisabeth A

2011-12-01

The primate orbitofrontal cortex (OFC) is often treated as a single entity, but architectonic and connectional neuroanatomy indicate that it has distinguishable parts. Nevertheless, few studies have attempted to dissociate the functions of its subregions. Here we review findings from recent neuropsychological and neurophysiological studies that do so. The lateral OFC seems to be important for learning, representing, and updating specific object-reward associations. The medial OFC seems to be important for value comparisons and choosing among objects on that basis. Rather than viewing this dissociation of function in terms of learning versus choosing, however, we suggest that it reflects the distinction between contrasts and comparisons: differences versus similarities. Making use of high-dimensional representations that arise from the convergence of several sensory modalities, the lateral OFC encodes contrasts among outcomes. The medial OFC reduces these contrasting representations of value to a single dimension, a common currency, in order to compare alternative choices. © 2011 New York Academy of Sciences.

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety

PubMed Central

Hu, Yifan; Iordan, Alexandru D.; Moore, Matthew; Dolcos, Florin

2016-01-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain–personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. PMID:26371336

Double dissociation of structure-function relationships in memory and fluid intelligence observed with magnetic resonance elastography.

PubMed

Johnson, Curtis L; Schwarb, Hillary; Horecka, Kevin M; McGarry, Matthew D J; Hillman, Charles H; Kramer, Arthur F; Cohen, Neal J; Barbey, Aron K

2018-05-01

Brain tissue mechanical properties, measured in vivo with magnetic resonance elastography (MRE), have proven to be sensitive metrics of neural tissue integrity. Recently, our group has reported on the positive relationship between viscoelasticity of the hippocampus and performance on a relational memory task in healthy young adults, which highlighted the potential of sensitive MRE measures for studying brain health and its relation to cognitive function; however, structure-function relationships outside of the hippocampus have not yet been explored. In this study, we examined the relationships between viscoelasticity of both the hippocampus and the orbitofrontal cortex and performance on behavioral assessments of relational memory and fluid intelligence. In a sample of healthy, young adults (N = 53), there was a significant, positive relationship between orbitofrontal cortex viscoelasticity and fluid intelligence performance (r = 0.42; p = .002). This finding is consistent with the previously reported relationship between hippocampal viscoelasticity and relational memory performance (r = 0.41; p = .002). Further, a significant double dissociation between the orbitofrontal-fluid intelligence relationship and the hippocampal-relational memory relationship was observed. These data support the specificity of regional brain MRE measures in support of separable cognitive functions. This report of a structure-function relationship observed with MRE beyond the hippocampus suggests a future role for MRE as a sensitive neuroimaging technique for brain mapping. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormalities in cortical gray matter density in borderline personality disorder

PubMed Central

Rossi, Roberta; Lanfredi, Mariangela; Pievani, Michela; Boccardi, Marina; Rasser, Paul E; Thompson, Paul M; Cavedo, Enrica; Cotelli, Maria; Rosini, Sandra; Beneduce, Rossella; Bignotti, Stefano; Magni, Laura R; Rillosi, Luciana; Magnaldi, Silvia; Cobelli, Milena; Rossi, Giuseppe; Frisoni, Giovanni B

2015-01-01

Background Borderline personality disorder (BPD) is a chronic condition with a strong impact on patients‘ affective,cognitive and social functioning. Neuroimaging techniques offer invaluable tools to understand the biological substrate of the disease. We aimed to investigate gray matter alterations over the whole cortex in a group of Borderline Personality Disorder (BPD) patients compared to healthy controls (HC). Methods Magnetic resonance-based cortical pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD patients and in their age- and sex-matched HC (age: 38±11; females: 16, 61%). Results BPD patients showed widespread lower cortical GMD compared to HC (4% difference) with peaks of lower density located in the dorsal frontal cortex, in the orbitofrontal cortex, the anterior and posterior cingulate, the right parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and in the visual cortex (p<0.005). Our BPD subjects displayed a symmetric distribution of anomalies in the dorsal aspect of the cortical mantle, but a wider involvement of the left hemisphere in the mesial aspect in terms of lower density. A few restricted regions of higher density were detected in the right hemisphere. All regions remained significant after correction for multiple comparisons via permutation testing. Conclusions BPD patients feature specific morphology of the cerebral structures involved in cognitive and emotional processing and social cognition/mentalization, consistent with clinical and functional data. PMID:25561291

Neural substrate of the late positive potential in emotional processing

PubMed Central

Liu, Yuelu; Huang, Haiqing; McGinnis, Menton; Keil, Andreas; Ding, Mingzhou

2012-01-01

The late positive potential (LPP) is a reliable electrophysiological index of emotional perception in humans. Despite years of research the brain structures that contribute to the generation and modulation of LPP are not well understood. Recording EEG and fMRI simultaneously, and applying a recently proposed single-trial ERP analysis method, we addressed the problem by correlating the single-trial LPP amplitude evoked by affective pictures with the blood-oxygen-level-dependent (BOLD) activity. Three results were found. First, relative to neutral pictures, pleasant and unpleasant pictures elicited enhanced LPP, as well as heightened BOLD activity in both visual cortices and emotion-processing structures such as amygdala and prefrontal cortex, consistent with previous findings. Second, the LPP amplitude across three picture categories was significantly correlated with BOLD activity in visual cortices, temporal cortices, amygdala, orbitofrontal cortex, and insula. Third, within each picture category, LPP-BOLD coupling revealed category-specific differences. For pleasant pictures, the LPP amplitude was coupled with BOLD in occipitotemporal junction, medial prefrontal cortex, amygdala, and precuneus, whereas for unpleasant pictures, significant LPP-BOLD correlation was observed in ventrolateral prefrontal cortex, insula, and posterior cingulate cortex. These results suggest that LPP is generated and modulated by an extensive brain network comprised of both cortical and subcortical structures associated with visual and emotional processing and the degree of contribution by each of these structures to the LPP modulation is valence-specific. PMID:23077042

Emotion and attention interactions in social cognition: brain regions involved in processing anger prosody.

PubMed

Sander, David; Grandjean, Didier; Pourtois, Gilles; Schwartz, Sophie; Seghier, Mohamed L; Scherer, Klaus R; Vuilleumier, Patrik

2005-12-01

Multiple levels of processing are thought to be involved in the appraisal of emotionally relevant events, with some processes being engaged relatively independently of attention, whereas other processes may depend on attention and current task goals or context. We conducted an event-related fMRI experiment to examine how processing angry voice prosody, an affectively and socially salient signal, is modulated by voluntary attention. To manipulate attention orthogonally to emotional prosody, we used a dichotic listening paradigm in which meaningless utterances, pronounced with either angry or neutral prosody, were presented simultaneously to both ears on each trial. In two successive blocks, participants selectively attended to either the left or right ear and performed a gender-decision on the voice heard on the target side. Our results revealed a functional dissociation between different brain areas. Whereas the right amygdala and bilateral superior temporal sulcus responded to anger prosody irrespective of whether it was heard from a to-be-attended or to-be-ignored voice, the orbitofrontal cortex and the cuneus in medial occipital cortex showed greater activation to the same emotional stimuli when the angry voice was to-be-attended rather than to-be-ignored. Furthermore, regression analyses revealed a strong correlation between orbitofrontal regions and sensitivity on a behavioral inhibition scale measuring proneness to anxiety reactions. Our results underscore the importance of emotion and attention interactions in social cognition by demonstrating that multiple levels of processing are involved in the appraisal of emotionally relevant cues in voices, and by showing a modulation of some emotional responses by both the current task-demands and individual differences.

Functional changes of the reward system underlie blunted response to social gaze in cocaine users

PubMed Central

Preller, Katrin H.; Herdener, Marcus; Schilbach, Leonhard; Stämpfli, Philipp; Hulka, Lea M.; Vonmoos, Matthias; Ingold, Nina; Vogeley, Kai; Tobler, Philippe N.; Seifritz, Erich; Quednow, Boris B.

2014-01-01

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction. PMID:24449854

Selective attention to affective value alters how the brain processes taste stimuli.

PubMed

Grabenhorst, Fabian; Rolls, Edmund T

2008-02-01

How does selective attention to affect influence sensory processing? In an fMRI investigation, when subjects were instructed to remember and rate the pleasantness of a taste stimulus, 0.1 M monosodium glutamate, activations were greater in the medial orbitofrontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the taste. When the subjects were instructed to remember and rate the intensity, activations were greater in the insular taste cortex. An interaction analysis showed that this dissociation of taste processing, depending on whether attention to pleasantness or intensity was relevant, was highly significant (P < 0.0002). Thus, depending on the context in which tastes are presented and whether affect is relevant, the brain responds to a taste differently. These findings show that, when attention is paid to affective value, the brain systems engaged to represent the sensory stimulus of taste are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus, depending on whether the cognitive demand is for affect-related vs. more sensory-related processing, may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of taste but also of other sensory stimuli.

The Essential Role of Primate Orbitofrontal Cortex in Conflict-Induced Executive Control Adjustment

PubMed Central

Buckley, Mark J.; Tanaka, Keiji

2014-01-01

Conflict in information processing evokes trial-by-trial behavioral modulations. Influential models suggest that adaptive tuning of executive control, mediated by mid-dorsal lateral prefrontal cortex (mdlPFC) and anterior cingulate cortex (ACC), underlies these modulations. However, mdlPFC and ACC are parts of distributed brain networks including orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), and superior-dorsal lateral prefrontal cortex (sdlPFC). Contributions of these latter areas in adaptive tuning of executive control are unknown. We trained monkeys to perform a matching task in which they had to resolve the conflict between two behavior-guiding rules. Here, we report that bilateral lesions in OFC, but not in PCC or sdlPFC, impaired selection between these competing rules. In addition, the behavioral adaptation that is normally induced by experiencing conflict disappeared in OFC-lesioned, but remained normal in PCC-lesioned or sdlPFC-lesioned monkeys. Exploring underlying neuronal processes, we found that the activity of neurons in OFC represented the conflict between behavioral options independent from the other aspects of the task. Responses of OFC neurons to rewards also conveyed information of the conflict level that the monkey had experienced along the course to obtain the reward. Our findings indicate dissociable functions for five closely interconnected cortical areas suggesting that OFC and mdlPFC, but not PCC or sdlPFC or ACC, play indispensable roles in conflict-dependent executive control of on-going behavior. Both mdlPFC and OFC support detection of conflict and its integration with the task goal, but in contrast to mdlPFC, OFC does not retain the necessary information for conflict-induced modulation of future decisions. PMID:25122901

Cocaine cue–induced dopamine release in the human prefrontal cortex

PubMed Central

Milella, Michele S.; Fotros, Aryandokht; Gravel, Paul; Casey, Kevin F.; Larcher, Kevin; Verhaeghe, Jeroen A.J.; Cox, Sylvia M.L.; Reader, Andrew J.; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

2016-01-01

Background Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Results Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. Conclusion In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms. PMID:26900792

Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

PubMed

Chudasama, Y; Robbins, Trevor W

2003-09-24

To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.

[Mental Space Navigation and Mental Time Travel].

PubMed

Kawamura, Mitsuru

2017-11-01

We examined patients with mental space navigation or mental time travel disorder to identify regions in the brain that may play a critical role in mental time travel in terms of clinical neuropsychology. These regions included the precneus, posterior cingulate gyrus, retrosplenial cortex, and hippocampus, as well as the orbitofrontal cortex: the anterior and posterior medial areas were both shown to be important in this process. Further studies are required to define whether these form a network for mental time travel.

Serotonin Transporter Knockout Rats Show Improved Strategy Set-Shifting and Reduced Latent Inhibition

ERIC Educational Resources Information Center

Nonkes, Lourens J. P.; van de Vondervoort, Ilse I. G. M.; de Leeuw, Mark J. C.; Wijlaars, Linda P.; Maes, Joseph H. R.; Homberg, Judith R.

2012-01-01

Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT[superscript -/-]) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting…

Multispectral brain morphometry in Tourette syndrome persisting into adulthood

PubMed Central

Martino, Davide; Cavanna, Andrea E.; Hutton, Chloe; Orth, Michael; Robertson, Mary M.; Critchley, Hugo D.; Frackowiak, Richard S.

2010-01-01

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change. PMID:21071387

Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of Attention Deficit Hyperactivity Disorder

PubMed Central

Somkuwar, Sucharita S.; Kantak, Kathleen M.; Dwoskin, Linda P.

2015-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in Spontaneously Hypertensive Rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax) x first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD. PMID:25680322

Marketing actions can modulate neural representations of experienced pleasantness.

PubMed

Plassmann, Hilke; O'Doherty, John; Shiv, Baba; Rangel, Antonio

2008-01-22

Despite the importance and pervasiveness of marketing, almost nothing is known about the neural mechanisms through which it affects decisions made by individuals. We propose that marketing actions, such as changes in the price of a product, can affect neural representations of experienced pleasantness. We tested this hypothesis by scanning human subjects using functional MRI while they tasted wines that, contrary to reality, they believed to be different and sold at different prices. Our results show that increasing the price of a wine increases subjective reports of flavor pleasantness as well as blood-oxygen-level-dependent activity in medial orbitofrontal cortex, an area that is widely thought to encode for experienced pleasantness during experiential tasks. The paper provides evidence for the ability of marketing actions to modulate neural correlates of experienced pleasantness and for the mechanisms through which the effect operates.

Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task.

PubMed

Zeeb, Fiona D; Baarendse, P J J; Vanderschuren, L J M J; Winstanley, Catharine A

2015-12-01

Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear. We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making. Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 μg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 μg/side). Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference. Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.

fMRI responses to pictures of mutilation and contamination.

PubMed

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

2006-01-30

Findings from several functional magnetic resonance imaging (fMRI) studies implicate the existence of a distinct neural disgust substrate, whereas others support the idea of distributed and integrative brain systems involved in emotional processing. In the present fMRI experiment 12 healthy females viewed pictures from four emotion categories. Two categories were disgust-relevant and depicted contamination or mutilation. The other scenes showed attacks (fear) or were affectively neutral. The two types of disgust elicitors received comparable ratings for disgust, fear and arousal. Both were associated with activation of the occipitotemporal cortex, the amygdala, and the orbitofrontal cortex; insula activity was nonsignificant in the two disgust conditions. Mutilation scenes induced greater inferior parietal activity than contamination scenes, which might mirror their greater capacity to capture attention. Our results are in disagreement with the idea of selective disgust processing at the insula. They point to a network of brain regions involved in the decoding of stimulus salience and the regulation of attention.

Inactivation of the Ventrolateral Orbitofrontal Cortex Impairs Flexible Use of Safety Signals.

PubMed

Sarlitto, Mary C; Foilb, Allison R; Christianson, John P

2018-05-21

Survival depends on adaptation to shifting environmental risks and opportunities. Regarding risks, the mechanisms which permit acquisition, recall, and flexible use of aversive associations is poorly understood. Drawing on the evidence that the orbital frontal cortex is critical to integrating outcome expectancies with flexible appetitive behavioral responses, we hypothesized that OFC would contribute to behavioral flexibility within an aversive learning domain. We introduce a fear conditioning procedure in which adult male rats were presented with shock-paired conditioned stimulus (CS+) or a safety cue (CS-). In a recall test, rats exhibit greater freezing to the CS+ than the CS-. Temporary inactivation of the ventrolateral OFC with muscimol prior to conditioning did not affect later discrimination, but inactivation after learning and prior to recall impaired discrimination between safety and danger cues. This result complements prior research in the appetitive domain and suggests that the OFC plays a general role in behavioral flexibility regardless of the valence of the CS. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering.

PubMed

Sitek, Kevin R; Cai, Shanqing; Beal, Deryk S; Perkell, Joseph S; Guenther, Frank H; Ghosh, Satrajit S

2016-01-01

Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers.

The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans

PubMed Central

Alsalman, Ola; Ost, Jan; Vanspauwen, Robby; Blaivie, Catherine; De Ridder, Dirk; Vanneste, Sven

2016-01-01

Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic symptoms of vertigo episodes. This suggests that these patients have a neural signature or trait that makes them prone to developing chronic balance problems. PMID:27089185

Induction of hyperphagia and carbohydrate intake by mu-opioid receptor stimulation in circumscribed regions of frontal cortex

PubMed Central

Mena, Jesus D.; Sadeghian, Ken; Baldo, Brian A.

2011-01-01

Frontal cortical regions are activated by food-associated stimuli, and this activation appears to be dysregulated in individuals with eating disorders. Nevertheless, frontal control of basic unconditioned feeding responses remains poorly understood. Here we show that hyperphagia can be driven by μ-opioid receptor stimulation in restricted regions of ventral medial prefrontal cortex (vmPFC) and orbitofrontal cortex. In both ad libitum-fed and food-restricted male Sprague-Dawley rats, bilateral infusions of the μ-opioid agonist, DAMGO, markedly increased intake of standard rat chow. When given a choice between palatable fat- versus carbohydrate enriched test diets, intra-vmPFC DAMGO infusions selectively increased carbohydrate intake, even in rats with a baseline fat preference. Rats also exhibited motor hyperactivity characterized by rapid switching between brief bouts of investigatory and ingestive behaviors. Intra-vmPFC DAMGO affected neither water intake nor non-specific oral behavior. Similar DAMGO infusions into neighboring areas of lateral orbital or anterior motor cortex had minimal effects on feeding. Neither stimulation of vmPFC-localized delta-opioid, kappa-opioid, dopaminergic, serotonergic, or noradrenergic receptors, nor antagonism of D1, 5HT1A, or alpha- or beta-adrenoceptors, reproduced the profile of DAMGO effects. Muscimol-mediated inactivation of the vmPFC, and intra-vmPFC stimulation of κ-opioid receptors or blockade of 5HT2A receptors, suppressed motor activity and increased feeding bout duration-a profile opposite to that seen with DAMGO. Hence, μ-opioid-induced hyperphagia and carbohydrate intake can be elicited with remarkable pharmacological and behavioral specificity from discrete subterritories of the frontal cortex. These findings may have implications for understanding affect-driven feeding and loss of restraint in eating disorders. PMID:21368037

Induction of hyperphagia and carbohydrate intake by μ-opioid receptor stimulation in circumscribed regions of frontal cortex.

PubMed

Mena, Jesus D; Sadeghian, Ken; Baldo, Brian A

2011-03-02

Frontal cortical regions are activated by food-associated stimuli, and this activation appears to be dysregulated in individuals with eating disorders. Nevertheless, frontal control of basic unconditioned feeding responses remains poorly understood. Here we show that hyperphagia can be driven by μ-opioid receptor stimulation in restricted regions of ventral medial prefrontal cortex (vmPFC) and orbitofrontal cortex. In both ad libitum-fed and food-restricted male Sprague Dawley rats, bilateral infusions of the μ-opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) markedly increased intake of standard rat chow. When given a choice between palatable fat-enriched versus carbohydrate-enriched test diets, intra-vmPFC DAMGO infusions selectively increased carbohydrate intake, even in rats with a baseline fat preference. Rats also exhibited motor hyperactivity characterized by rapid switching between brief bouts of investigatory and ingestive behaviors. Intra-vmPFC DAMGO affected neither water intake nor nonspecific oral behavior. Similar DAMGO infusions into neighboring areas of lateral orbital or anterior motor cortex had minimal effects on feeding. Neither stimulation of vmPFC-localized δ-opioid, κ-opioid, dopaminergic, serotonergic, or noradrenergic receptors, nor antagonism of D1, 5HT1A, or α- or β-adrenoceptors, reproduced the profile of DAMGO effects. Muscimol-mediated inactivation of the vmPFC, and intra-vmPFC stimulation of κ-opioid receptors or blockade of 5-HT2A (5-hydroxytryptamine receptor 2A) receptors, suppressed motor activity and increased feeding bout duration-a profile opposite to that seen with DAMGO. Hence, μ-opioid-induced hyperphagia and carbohydrate intake can be elicited with remarkable pharmacological and behavioral specificity from discrete subterritories of the frontal cortex. These findings may have implications for understanding affect-driven feeding and loss of restraint in eating disorders.

The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans.

PubMed

Alsalman, Ola; Ost, Jan; Vanspauwen, Robby; Blaivie, Catherine; De Ridder, Dirk; Vanneste, Sven

2016-01-01

Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic symptoms of vertigo episodes. This suggests that these patients have a neural signature or trait that makes them prone to developing chronic balance problems.

Telling good from bad news: ADHD differentially affects processing of positive and negative feedback during guessing.

PubMed

van Meel, Catharina S; Oosterlaan, Jaap; Heslenfeld, Dirk J; Sergeant, Joseph A

2005-01-01

Neuroimaging studies on ADHD suggest abnormalities in brain regions associated with decision-making and reward processing such as the anterior cingulate cortex (ACC) and orbitofrontal cortex. Recently, event-related potential (ERP) studies demonstrated that the ACC is involved in processing feedback signals during guessing and gambling. The resulting negative deflection, the 'feedback-related negativity' (FRN) has been interpreted as reflecting an error in reward prediction. In the present study, ERPs elicited by positive and negative feedback were recorded in children with ADHD and normal controls during guessing. 'Correct' and 'incorrect' guesses resulted in respectively monetary gains and losses. The FRN amplitude to losses was more pronounced in the ADHD group than in normal controls. Positive and negative feedback differentially affected long latency components in the ERP waveforms of normal controls, but not ADHD children. These later deflections might be related to further emotional or strategic processing. The present findings suggest an enhanced sensitivity to unfavourable outcomes in children with ADHD, probably due to abnormalities in mesolimbic reward circuits. In addition, further processing, such as affective evaluation and the assessment of future consequences of the feedback signal seems to be altered in ADHD. These results may further help understanding the neural basis of decision-making deficits in ADHD.

Bilateral limbic system destruction in man

PubMed Central

Feinstein, Justin S.; Rudrauf, David; Khalsa, Sahib S.; Cassell, Martin D.; Bruss, Joel; Grabowski, Thomas J.; Tranel, Daniel

2010-01-01

We report here a case study of a rare neurological patient with bilateral brain damage encompassing a substantial portion of the so-called “limbic system.” The patient, Roger, has been studied in our laboratory for over 14 years and the current article presents his complete neuroanatomical and neuropsychological profiles. The brain damage occurred in 1980 following an episode of herpes simplex encephalitis. The amount of destroyed neural tissue is extensive and includes bilateral damage to core limbic and paralimbic regions, including the hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right hemisphere is more extensively affected than the left, although the lesions are largely bilateral. Despite the magnitude of his brain damage, Roger has a normal IQ, average to above average attention, working memory, and executive functioning skills, and very good speech and language abilities. In fact, his only obvious presenting deficits are a dense global amnesia and a severe anosmia and ageusia. Roger's case presents a rare opportunity to advance our understanding of the critical functions underlying the human limbic system, and the neuropsychological and neuroanatomical data presented here provide a critical foundation for such investigations. PMID:19763994

Body-part-specific representations of semantic noun categories.

PubMed

Carota, Francesca; Moseley, Rachel; Pulvermüller, Friedemann

2012-06-01

Word meaning processing in the brain involves ventrolateral temporal cortex, but a semantic contribution of the dorsal stream, especially frontocentral sensorimotor areas, has been controversial. We here examine brain activation during passive reading of object-related nouns from different semantic categories, notably animal, food, and tool words, matched for a range of psycholinguistic features. Results show ventral stream activation in temporal cortex along with category-specific activation patterns in both ventral and dorsal streams, including sensorimotor systems and adjacent pFC. Precentral activation reflected action-related semantic features of the word categories. Cortical regions implicated in mouth and face movements were sparked by food words, and hand area activation was seen for tool words, consistent with the actions implicated by the objects the words are used to speak about. Furthermore, tool words specifically activated the right cerebellum, and food words activated the left orbito-frontal and fusiform areas. We discuss our results in the context of category-specific semantic deficits in the processing of words and concepts, along with previous neuroimaging research, and conclude that specific dorsal and ventral areas in frontocentral and temporal cortex index visual and affective-emotional semantic attributes of object-related nouns and action-related affordances of their referent objects.

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards

PubMed Central

Smoski, Moria J.; Rittenberg, Alison; Dichter, Gabriel S.

2011-01-01

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during fMRI scanning to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and thirteen affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. PMID:22079658

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

PubMed

Smoski, Moria J; Rittenberg, Alison; Dichter, Gabriel S

2011-12-30

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. 2011 Elsevier Ireland Ltd. All rights reserved.

Brain Systems for Assessing Facial Attractiveness

ERIC Educational Resources Information Center

Winston, Joel S.; O'Doherty, John; Kilner, James M.; Perrett, David I.; Dolan, Raymond J.

2007-01-01

Attractiveness is a facial attribute that shapes human affiliative behaviours. In a previous study we reported a linear response to facial attractiveness in orbitofrontal cortex (OFC), a region involved in reward processing. There are strong theoretical grounds for the hypothesis that coding stimulus reward value also involves the amygdala. The…

Adverse Effects of Cannabis on Adolescent Brain Development: A Longitudinal Study.

PubMed

Camchong, Jazmin; Lim, Kelvin O; Kumra, Sanjiv

2017-03-01

Cannabis is widely perceived as a safe recreational drug and its use is increasing in youth. It is important to understand the implications of cannabis use during childhood and adolescence on brain development. This is the first longitudinal study that compared resting functional connectivity of frontally mediated networks between 43 healthy controls (HCs; 20 females; age M = 16.5 ± 2.7) and 22 treatment-seeking adolescents with cannabis use disorder (CUD; 8 females; age M = 17.6 ± 2.4). Increases in resting functional connectivity between caudal anterior cingulate cortex (ACC) and superior frontal gyrus across time were found in HC, but not in CUD. CUD showed a decrease in functional connectivity between caudal ACC and dorsolateral and orbitofrontal cortices across time. Lower functional connectivity between caudal ACC cortex and orbitofrontal cortex at baseline predicted higher amounts of cannabis use during the following 18 months. Finally, high amounts of cannabis use during the 18-month interval predicted lower intelligence quotient and slower cognitive function measured at follow-up. These data provide compelling longitudinal evidence suggesting that repeated exposure to cannabis during adolescence may have detrimental effects on brain resting functional connectivity, intelligence, and cognitive function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Associations of religious behavior and experiences with extent of regional atrophy in the orbitofrontal cortex during older adulthood

PubMed Central

Hayward, R. David; Owen, Amy D.; Koenig, Harold G.; Steffens, David C.; Payne, Martha E.

2011-01-01

The orbitofrontal cortex (OFC) is a region of the brain that has been empirically linked with religious or spiritual activity, and atrophy in this region has been shown to contribute to serious mental illness in late life. This study used structural magnetic resonance imaging to examine the association between religious or spiritual factors and volume of the orbitalfrontal cortex (OFC). Change in the volume of participants’ left and right OFC was measured longitudinally over a period of two to eight years. Multiple linear regression analyses showed that religious or spiritual factors were related to extent of atrophy in the left OFC. Significantly less atrophy of the left OFC was observed in participants who reported a life-changing religious or spiritual experience during the course of the study, and in members of Protestant religious groups who reported being born-again when entering the study. Significantly greater atrophy of the left OFC was also associated with more frequent participation in public religious worship. No significant relationship was observed between religious or spiritual factors and extent of atrophy in the right OFC. These results support the presence of a long-term relationship between religious or spiritual experience and brain structure, which may have clinical implications. PMID:22611519

Old proverbs in new skins - an FMRI study on defamiliarization.

PubMed

Bohrn, Isabel C; Altmann, Ulrike; Lubrich, Oliver; Menninghaus, Winfried; Jacobs, Arthur M

2012-01-01

We investigated how processing fluency and defamiliarization (the art of rendering familiar notions unfamiliar) contribute to the affective and esthetic processing of reading in an event-related functional magnetic-resonance-imaging experiment. We compared the neural correlates of processing (a) familiar German proverbs, (b) unfamiliar proverbs, (c) defamiliarized variations with altered content relative to the original proverb (proverb-variants), (d) defamiliarized versions with unexpected wording but the same content as the original proverb (proverb-substitutions), and (e) non-rhetorical sentences. Here, we demonstrate that defamiliarization is an effective way of guiding attention, but that the degree of affective involvement depends on the type of defamiliarization: enhanced activation in affect-related regions (orbito-frontal cortex, medPFC) was found only if defamiliarization altered the content of the original proverb. Defamiliarization on the level of wording was associated with attention processes and error monitoring. Although proverb-variants evoked activation in affect-related regions, familiar proverbs received the highest beauty ratings.

Old Proverbs in New Skins – An fMRI Study on Defamiliarization

PubMed Central

Bohrn, Isabel C.; Altmann, Ulrike; Lubrich, Oliver; Menninghaus, Winfried; Jacobs, Arthur M.

2012-01-01

We investigated how processing fluency and defamiliarization (the art of rendering familiar notions unfamiliar) contribute to the affective and esthetic processing of reading in an event-related functional magnetic-resonance-imaging experiment. We compared the neural correlates of processing (a) familiar German proverbs, (b) unfamiliar proverbs, (c) defamiliarized variations with altered content relative to the original proverb (proverb-variants), (d) defamiliarized versions with unexpected wording but the same content as the original proverb (proverb-substitutions), and (e) non-rhetorical sentences. Here, we demonstrate that defamiliarization is an effective way of guiding attention, but that the degree of affective involvement depends on the type of defamiliarization: enhanced activation in affect-related regions (orbito-frontal cortex, medPFC) was found only if defamiliarization altered the content of the original proverb. Defamiliarization on the level of wording was associated with attention processes and error monitoring. Although proverb-variants evoked activation in affect-related regions, familiar proverbs received the highest beauty ratings. PMID:22783212

Brain Cortical Thickness Differences in Adolescent Females with Substance Use Disorders.

PubMed

Boulos, Peter K; Dalwani, Manish S; Tanabe, Jody; Mikulich-Gilbertson, Susan K; Banich, Marie T; Crowley, Thomas J; Sakai, Joseph T

2016-01-01

We recruited right-handed female patients, 14-19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses. A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size). Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.

Uncinate fasciculus fractional anisotropy correlates with typical use of reappraisal in women but not men.

PubMed

Zuurbier, Lisette A; Nikolova, Yuliya S; Ahs, Fredrik; Hariri, Ahmad R

2013-06-01

Emotion regulation refers to strategies through which individuals influence their experience and expression of emotions. Two typical strategies are reappraisal, a cognitive strategy for reframing the context of an emotional experience, and suppression, a behavioral strategy for inhibiting emotional responses. Functional neuroimaging studies have revealed that regions of the prefrontal cortex modulate amygdala reactivity during both strategies, but relatively greater downregulation of the amygdala occurs during reappraisal. Moreover, these studies demonstrated that engagement of this modulatory circuitry varies as a function of gender. The uncinate fasciculus is a major structural pathway connecting regions of the anterior temporal lobe, including the amygdala to inferior frontal regions, especially the orbitofrontal cortex. The objective of the current study was to map variability in the structural integrity of the uncinate fasciculus onto individual differences in self-reported typical use of reappraisal and suppression. Diffusion tensor imaging was used in 194 young adults to derive regional fractional anisotropy values for the right and left uncinate fasciculus. All participants also completed the Emotion Regulation Questionnaire. In women but not men, self-reported typical reappraisal use was positively correlated with fractional anisotropy values in a region of the left uncinate fasciculus within the orbitofrontal cortex. In contrast, typical use of suppression was not significantly correlated with fractional anisotropy in any region of the uncinate fasciculus in either men or women. Our data suggest that in women typical reappraisal use is specifically related to the integrity of white matter pathways linking the amygdala and prefrontal cortex.

Orbitofrontal Gray Matter Relates to Early Morning Awakening: A Neural Correlate of Insomnia Complaints?

PubMed Central

Stoffers, Diederick; Moens, Sarah; Benjamins, Jeroen; van Tol, Marie-José; Penninx, Brenda W. J. H.; Veltman, Dick J.; Van der Wee, Nic J. A.; Van Someren, Eus J. W.

2012-01-01

Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18–56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated. PMID:23060850

Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex.

PubMed

Kahnt, Thorsten; Tobler, Philippe N

2017-02-08

Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D 2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks. SIGNIFICANCE STATEMENT A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D 2 receptors has profound effects on the functional connectivity patterns of the OFC, yielding altered connectivity-based subdivisions of this region. Our results suggest that dopamine changes the connectional configuration of the OFC, possibly leading to transitions between different operating modes that favor either sensory input or recurrent processing in the prefrontal cortex. More generally, our findings support a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks and may have clinical implications for understanding the actions of antipsychotic agents. Copyright © 2017 the authors 0270-6474/17/371493-12$15.00/0.

Identity-Specific Reward Representations in Orbitofrontal Cortex Are Modulated by Selective Devaluation.

PubMed

Howard, James D; Kahnt, Thorsten

2017-03-08

Goal-directed behavior is sensitive to the current value of expected outcomes. This requires independent representations of specific rewards, which have been linked to orbitofrontal cortex (OFC) function. However, the mechanisms by which the human brain updates specific goals on the fly, and translates those updates into choices, have remained unknown. Here we implemented selective devaluation of appetizing food odors in combination with pattern-based neuroimaging and a decision-making task. We found that in a hungry state, participants chose to smell high-intensity versions of two value-matched food odor rewards. After eating a meal corresponding to one of the two odors, participants switched choices toward the low intensity of the sated odor but continued to choose the high intensity of the nonsated odor. This sensory-specific behavioral effect was mirrored by pattern-based changes in fMRI signal in lateral posterior OFC, where specific reward identity representations were altered after the meal for the sated food odor but retained for the nonsated counterpart. In addition, changes in functional connectivity between the OFC and general value coding in ventromedial prefrontal cortex (vmPFC) predicted individual differences in satiety-related choice behavior. These findings demonstrate how flexible representations of specific rewards in the OFC are updated by devaluation, and how functional connections to vmPFC reflect the current value of outcomes and guide goal-directed behavior. SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) is critical for goal-directed behavior. A recent proposal is that OFC fulfills this function by representing a variety of state and task variables ("cognitive maps"), including a conjunction of expected reward identity and value. Here we tested how identity-specific representations of food odor reward are updated by satiety. We found that fMRI pattern-based signatures of reward identity in lateral posterior OFC were modulated after selective devaluation, and that connectivity between this region and general value coding ventromedial prefrontal cortex (vmPFC) predicted choice behavior. These results provide evidence for a mechanism by which devaluation modulates a cognitive map of expected reward in OFC and thereby alters general value signals in vmPFC to guide goal-directed behavior. Copyright © 2017 the authors 0270-6474/17/372627-12$15.00/0.

BDNF-GSK-3β-β-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats.

PubMed

Xu, Ling-Zhi; Xu, De-Feng; Han, Ying; Liu, Li-Jing; Sun, Cheng-Yu; Deng, Jia-Hui; Zhang, Ruo-Xi; Yuan, Ming; Zhang, Su-Zhen; Li, Zhi-Meng; Xu, Yi; Li, Jin-Sheng; Xie, Su-Hua; Li, Su-Xia; Zhang, Hong-Yan; Lu, Lin

2017-01-01

Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3β in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3β, β-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3β by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3β, and β-catenin in the medial prefrontal cortex. Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Neural correlates of strategic processes underlying episodic memory in women with major depression: A 15O-PET study.

PubMed

Ottowitz, William E; Deckersbach, Thilo; Savage, Cary R; Lindquist, Martin A; Dougherty, Darin D

2010-01-01

To evaluate the functional integrity of brain regions underlying strategic mnemonic processing in patients with major depressive disorder, the authors administered a modified version of the California Verbal Learning Test to depressed patients during presentation of lists of unrelated words and, conversely, during presentation of lists of related words with and without orientation regarding the relatedness of the words (eight healthy females, IQ=122, and eight depressed females, IQ=107). Brain function evaluated across all three conditions showed that patients with major depressive disorder revealed activation of the right anterior cingulate cortex, left ventrolateral prefrontal cortex, both hippocampi, and the left orbitofrontal cortex. Further analysis showed that patients with major depressive disorder had greater activation of the right anterior cingulate cortex during semantic organization and the right ventrolateral prefrontal cortex during strategy initiation.

A Preliminary Study of the Human Brain Response to Oral Sucrose and its Association with Recent Drinking

PubMed Central

Kareken, David A.; Dzemidzic, Mario; Oberlin, Brandon G.; Eiler, William J.A.

2014-01-01

Background A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards. Methods Sixteen right-handed, non-treatment seeking, healthy volunteers (mean age 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83M concentration of sucrose in water. Results [Sucrose > Water] provoked significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose-liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R= 0.79, p = 0.002). Conclusions Both the orbitofrontal response to an intensely sweet taste, as well as rated liking of that taste, accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk. PMID:23841808

What is the impact of child abuse on gray matter abnormalities in individuals with major depressive disorder: a case control study.

PubMed

Ahn, Sung Jun; Kyeong, Sunghyon; Suh, Sang Hyun; Kim, Jae-Jin; Chung, Tae-Sub; Seok, Jeong-Ho

2016-11-14

Patients with major depressive disorder (MDD) present heterogeneous clinical symptoms, and childhood abuse is associated with deepening of psychopathology. The aim of this study was to identify structural brain abnormalities in MDD and to assess further differences in gray matter density (GMD) associated with childhood abuse in MDD. Differences in regional GMD between 34 MDD patients and 26 healthy controls were assessed using magnetic resonance imaging and optimized voxel-based morphometry. Within the MDD group, further comparisons were performed focusing on the experience of maltreatment during childhood (23 MDD with child abuse vs 11 MDD without child abuse). Compared with healthy controls, the MDD patient group showed decreased GMD in the bilateral orbitofrontal cortices, right superior frontal gyrus, right posterior cingulate gyrus, bilateral middle occipital gyri, and left cuneus. In addition, the patient group showed increased GMD in bilateral postcentral gyri, parieto-occipital cortices, putamina, thalami, and hippocampi, and left cerebellar declive and tuber of vermis. Within the MDD patient group, the subgroup with abuse showed a tendency of decreased GMD in right orbitofrontal cortex, but showed increased GMD in the left postcentral gyrus compared to the subgroup without abuse. Our findings suggest a complicated dysfunction of networks between cortical-subcortical circuits in MDD. In addition, increased GMD in postcentral gyrus and a possible reduction of GMD in the orbitofrontal cortex of MDD patients with abuse subgroup may be associated with abnormalities of body perception and emotional dysregulation.

Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597.

PubMed

Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

2016-09-01

The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Pavlovian valuation systems in learning and decision making

PubMed Central

Clark, Jeremy J.; Hollon, Nick G.; Phillips, Paul E. M.

2012-01-01

Environmental stimuli guide value-based decision making, but can do so through cognitive representation of outcomes or through general-incentive properties attributed to the cues themselves. We assert that these differences are conferred through the use of alternative associative structures differing in computational intensity. Using this framework, we review scientific evidence to discern the neural substrates of these assumed separable processes. We suggest that the contribution of the mesolimbic dopamine system to Pavlovian valuation is restricted to an affective system that is only updated through experiential feedback of stimulus-outcome pairing, whereas the orbitofrontal cortex contributes to an alternative system capable of inferential reasoning. Finally we discuss the interactions and convergence of these systems and their implications for decision making and its pathology. PMID:22749132

Obsessive Compulsive Disorder: Beyond Segregated Cortico-striatal Pathways

PubMed Central

Milad, Mohammed R.; Rauch, Scott L.

2016-01-01

Obsessive-compulsive disorder (OCD) affects ∼2-3% of the population and is characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), typically performed in response to obsessions or related anxiety. In the past few decades, the prevailing models of OCD pathophysiology have focused on cortico-striatal circuitry. More recent neuroimaging evidence, however, points to critical involvement of the lateral and medial orbitofrontal cortices, the dorsal anterior cingulate cortex and amygdalo-cortical circuitry, in addition to cortico-striatal circuitry, in the pathophysiology of the disorder. In this review, we elaborate proposed features of OCD pathophysiology beyond the classic parallel cortico-striatal pathways and argue that this evidence suggests that fear extinction, in addition to behavioral inhibition, may be impaired in OCD. PMID:22138231

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers.

PubMed

Li, Xingbao; Du, Lian; Sahlem, Gregory L; Badran, Bashar W; Henderson, Scott; George, Mark S

2017-05-01

Previous studies reported that repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving and decrease cigarette consumption in smokers. The mechanism of this effect however, remains unclear. We used resting-state functional magnetic resonance imaging (rsfMRI) to test the effect of rTMS in non-treatment seeking smokers. We used a single blinded, sham-controlled, randomized counterbalanced crossover design where participants underwent two visits separated by at least 1 week. Participants received active rTMS over the left dorsolateral prefrontal cortex (DLPFC) during one of their visits, and sham rTMS during their other visit. They had two rsFMRI scans before and after each rTMS session. We used the same rTMS stimulation parameters as in a previous study (10Hz, 5s-on, 10s-off, 100% resting motor threshold, 3000 pulses). Ten non-treatment-seeking, nicotine-dependent, cigarette smokers (6 women, an average age of 39.72 and an average cigarette per day of 17.30) finished the study. rsFMRI results demonstrate that as compared to a single session of sham rTMS, a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation (fALFF). For intrinsic brain connectivity comparisons, active TMS resulted in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex. This data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF. The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct roles of three frontal cortical areas in reward-guided behavior

PubMed Central

Noonan, M.P.; Mars, R.B.; Rushworth, M.F.S

2011-01-01

Functional magnetic resonance imaging (fMRI) was used to measure activity in three frontal cortical areas, lateral orbitofrontal cortex (lOFC), medial orbitofrontal cortex/ventromedial frontal cortex (mOFC/vmPFC), and anterior cingulate cortex (ACC) when expectations about type of reward, and not just reward presence or absence, could be learned. Two groups of human subjects learned twelve stimulus-response pairings. In one group (Consistent), correct performances of a given pairing were always reinforced with a specific reward outcome whereas in the other group (Inconsistent), correct performances were reinforced with randomly selected rewards. MOFC/vmPFC and lOFC were not distinguished by simple differences in relative preference for positive and negative outcomes. Instead lOFC activity reflected updating of reward-related associations specific to reward type; lOFC was active whenever informative outcomes allowed updating of reward-related associations regardless of whether the outcomes were positive or negative and the effects were greater when consistent stimulus-outcome and response-outcome mappings were present. A psycho-physiological interaction (PPI) analysis demonstrated changed coupling between lOFC and brain areas for visual object representation, such as perirhinal cortex, and reward-guided learning, such as amygdala, ventral striatum, and habenula /mediodorsal thalamus. By contrast mOFC/vmPFC activity reflected expected values of outcomes and occurrence of positive outcomes, irrespective of consistency of outcome mappings. The third frontal cortical region, ACC, reflected the use of reward type information to guide response selection. ACC activity reflected the probability of selecting the correct response, was greater when consistent outcome mappings were present, and was related to individual differences in propensity to select the correct response. PMID:21976525

Strategies for tonal and atonal musical interpretation in blind and normally sighted children: an fMRI study.

PubMed

Guerrero Arenas, Coral; Hidalgo Tobón, Silvia S; Dies Suarez, Pilar; Barragán Pérez, Eduardo; Castro Sierra, Eduardo; García, Julio; de Celis Alonso, Benito

2016-04-01

Early childhood is known to be a period when cortical plasticity phenomena are at a maximum. Music is a stimulus known to modulate these mechanisms. On the other hand, neurological impairments like blindness are also known to affect cortical plasticity. Here, we address how tonal and atonal musical stimuli are processed in control and blind young children. We aimed to understand the differences between the two groups when processing this physiological information. Atonal stimuli produced larger activations in cerebellum, fusiform, and temporal lobe structures than tonal. In contrast, tonal stimuli induced larger frontal lobe representations than atonal. Control participants presented large activations in cerebellum, fusiform, and temporal lobe. A correlation/connectivity study showed that the blind group incorporated larger amounts of perceptual information (somatosensory and motor) into tonal processing through the function of the anterior prefrontal cortex (APC). They also used the visual cortex in conjunction with the Wernicke's area to process this information. In contrast, controls processed sound with perceptual stimuli from auditory cortex structures (including Wernicke's area). In this case, information was processed through the dorsal posterior cingulate cortex and not the APC. The orbitofrontal cortex also played a key role for atonal interpretation in this group. Wernicke's area, known to be involved in speech, was heavily involved for both groups and all stimuli. The two groups presented clear differences in strategies for music processing, with very different recruitment of brain regions.

Reduced Activation of Left Orbitofrontal Cortex Precedes Blocked Vocalization: A Magnetoencephalographic Study

ERIC Educational Resources Information Center

Sowman, Paul F.; Crain, Stephen; Harrison, Elisabeth; Johnson, Blake W.

2012-01-01

While stuttering is known to be characterized by anomalous brain activations during speech, very little data is available describing brain activations during stuttering. To our knowledge there are no reports describing brain activations that precede blocking. In this case report we present magnetoencephalographic data from a person who stutters…

Prioritising the relevant information for learning and decision making within orbital and ventromedial prefrontal cortex.

PubMed

Walton, Mark E; Chau, Bolton K H; Kennerley, Steven W

2015-02-01

Our environment and internal states are frequently complex, ambiguous and dynamic, meaning we need to have selection mechanisms to ensure we are basing our decisions on currently relevant information. Here, we review evidence that orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) play conserved, critical but distinct roles in this process. While OFC may use specific sensory associations to enhance task-relevant information, particularly in the context of learning, VMPFC plays a role in ensuring irrelevant information does not impinge on the decision in hand.

Frontotemporal networks and behavioral symptoms in primary progressive aphasia.

PubMed

D'Anna, Lucio; Mesulam, Marsel M; Thiebaut de Schotten, Michel; Dell'Acqua, Flavio; Murphy, Declan; Wieneke, Christina; Martersteck, Adam; Cobia, Derin; Rogalski, Emily; Catani, Marco

2016-04-12

To determine if behavioral symptoms in patients with primary progressive aphasia (PPA) were associated with degeneration of a ventral frontotemporal network. We used diffusion tensor imaging tractography to quantify abnormalities of the uncinate fasciculus that connects the anterior temporal lobe and the ventrolateral frontal cortex. Two additional ventral tracts were studied: the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus. We also measured cortical thickness of anterior temporal and orbitofrontal regions interconnected by these tracts. Thirty-three patients with PPA and 26 healthy controls were recruited. In keeping with the PPA diagnosis, behavioral symptoms were distinctly less prominent than the language deficits. Although all 3 tracts had structural pathology as determined by tractography, significant correlations with scores on the Frontal Behavioral Inventory were found only for the uncinate fasciculus. Cortical atrophy of the orbitofrontal and anterior temporal lobe cortex was also correlated with these scores. Our findings indicate that damage to a frontotemporal network mediated by the uncinate fasciculus may underlie the emergence of behavioral symptoms in patients with PPA. © 2016 American Academy of Neurology.

Frontotemporal networks and behavioral symptoms in primary progressive aphasia

PubMed Central

Mesulam, Marsel M.; Thiebaut de Schotten, Michel; Dell'Acqua, Flavio; Murphy, Declan; Wieneke, Christina; Martersteck, Adam; Cobia, Derin; Rogalski, Emily

2016-01-01

Objective: To determine if behavioral symptoms in patients with primary progressive aphasia (PPA) were associated with degeneration of a ventral frontotemporal network. Methods: We used diffusion tensor imaging tractography to quantify abnormalities of the uncinate fasciculus that connects the anterior temporal lobe and the ventrolateral frontal cortex. Two additional ventral tracts were studied: the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus. We also measured cortical thickness of anterior temporal and orbitofrontal regions interconnected by these tracts. Thirty-three patients with PPA and 26 healthy controls were recruited. Results: In keeping with the PPA diagnosis, behavioral symptoms were distinctly less prominent than the language deficits. Although all 3 tracts had structural pathology as determined by tractography, significant correlations with scores on the Frontal Behavioral Inventory were found only for the uncinate fasciculus. Cortical atrophy of the orbitofrontal and anterior temporal lobe cortex was also correlated with these scores. Conclusions: Our findings indicate that damage to a frontotemporal network mediated by the uncinate fasciculus may underlie the emergence of behavioral symptoms in patients with PPA. PMID:26992858

Neural Correlates of Appetite and Hunger-Related Evaluative Judgments

PubMed Central

Piech, Richard M.; Lewis, Jade; Parkinson, Caroline H.; Owen, Adrian M.; Roberts, Angela C.; Downing, Paul E.; Parkinson, John A.

2009-01-01

How much we desire a meal depends on both the constituent foods and how hungry we are, though not every meal becomes more desirable with increasing hunger. The brain therefore needs to be able to integrate hunger and meal properties to compute the correct incentive value of a meal. The present study investigated the functional role of the amygdala and the orbitofrontal cortex in mediating hunger and dish attractiveness. Furthermore, it explored neural responses to dish descriptions particularly susceptible to value-increase following fasting. We instructed participants to rate how much they wanted food menu items while they were either hungry or sated, and compared the rating differences in these states. Our results point to the representation of food value in the amygdala, and to an integration of attractiveness with hunger level in the orbitofrontal cortex. Dishes particularly desirable during hunger activated the thalamus and the insula. Our results specify the functions of evaluative structures in the context of food attractiveness, and point to a complex neural representation of dish qualities which contribute to state-dependent value. PMID:19672296

Neural correlates of appetite and hunger-related evaluative judgments.

PubMed

Piech, Richard M; Lewis, Jade; Parkinson, Caroline H; Owen, Adrian M; Roberts, Angela C; Downing, Paul E; Parkinson, John A

2009-08-12

How much we desire a meal depends on both the constituent foods and how hungry we are, though not every meal becomes more desirable with increasing hunger. The brain therefore needs to be able to integrate hunger and meal properties to compute the correct incentive value of a meal. The present study investigated the functional role of the amygdala and the orbitofrontal cortex in mediating hunger and dish attractiveness. Furthermore, it explored neural responses to dish descriptions particularly susceptible to value-increase following fasting. We instructed participants to rate how much they wanted food menu items while they were either hungry or sated, and compared the rating differences in these states. Our results point to the representation of food value in the amygdala, and to an integration of attractiveness with hunger level in the orbitofrontal cortex. Dishes particularly desirable during hunger activated the thalamus and the insula. Our results specify the functions of evaluative structures in the context of food attractiveness, and point to a complex neural representation of dish qualities which contribute to state-dependent value.

Tracking Emotional Valence: The Role of the Orbitofrontal Cortex

PubMed Central

Goodkind, Madeleine S.; Sollberger, Marc; Gyurak, Anett; Rosen, Howard J.; Rankin, Katherine; Miller, Bruce; Levenson, Robert

2011-01-01

Successful navigation of the social world requires the ability to recognize and track emotions as they unfold and change dynamically. Neuroimaging and neurological studies of emotion recognition have primarily focused on the ability to identify the emotion shown in static photographs of facial expressions, showing correlations with the amygdala as well as temporal and frontal brain regions. In the current study we examined the neural correlates of continuously tracking dynamically-changing emotions. Fifty-nine patients with diverse neurodegenerative diseases used a rating dial to track continuously how positive or how negative the character in a film clip felt. Tracking accuracy was determined by comparing participants’ ratings with the ratings of 10 normal control participants. The relationship between tracking accuracy and regional brain tissue content was examined using voxel-based morphometry. Low tracking accuracy was primarily associated with gray matter loss in the right lateral orbitofrontal cortex (OFC). Our finding that the right OFC is critical to the ability to track dynamically-changing emotions is consistent with previous research showing right OFC involvement in both socioemotional understanding and modifying responding in changing situations. PMID:21425397

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

PubMed

Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

2016-02-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Marketing actions can modulate neural representations of experienced pleasantness

PubMed Central

Plassmann, Hilke; O'Doherty, John; Shiv, Baba; Rangel, Antonio

2008-01-01

Despite the importance and pervasiveness of marketing, almost nothing is known about the neural mechanisms through which it affects decisions made by individuals. We propose that marketing actions, such as changes in the price of a product, can affect neural representations of experienced pleasantness. We tested this hypothesis by scanning human subjects using functional MRI while they tasted wines that, contrary to reality, they believed to be different and sold at different prices. Our results show that increasing the price of a wine increases subjective reports of flavor pleasantness as well as blood-oxygen-level-dependent activity in medial orbitofrontal cortex, an area that is widely thought to encode for experienced pleasantness during experiential tasks. The paper provides evidence for the ability of marketing actions to modulate neural correlates of experienced pleasantness and for the mechanisms through which the effect operates. PMID:18195362

Involvement of the Lateral Orbitofrontal Cortex in Drug Context-induced Reinstatement of Cocaine-seeking Behavior in Rats

PubMed Central

Lasseter, Heather C.; Ramirez, Donna R.; Xie, Xiaohu; Fuchs, Rita A.

2009-01-01

Orbitofrontal cortex (OFC) damage produces impaired decision-making, impulsivity, and perseveration and potentially contributes to compulsive drug seeking in cocaine users. To further explore this phenomenon, we assessed the role of the lateral OFC (lOFC) in drug context-induced cocaine-seeking behavior in the reinstatement model of drug relapse. Rats were trained to lever press for intravenous cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a different context (extinction-paired context). Reinstatement of cocaine seeking (non-reinforced lever presses) was assessed in the cocaine context in the absence of response-contingent stimuli. In experiment 1, we evaluated whether acute inhibition of lOFC output alters context-induced cocaine-seeking behavior by infusing the GABAB+A agonists, baclofen+muscimol, or vehicle into the lOFC immediately before exposure to the cocaine-paired context. In experiments 2–3, we assessed how prolonged loss of lOFC output affects drug context-induced cocaine seeking by administering bilateral NMDA or sham lesions of the lOFC either before or after self-administration and extinction training. Remarkably, OFC functional inactivation attenuated, post-training lesions failed to alter, and pre-training lesions potentiated drug context-induced cocaine seeking without altering responding in the extinction context. These results suggest that neural activity in the lOFC promotes context-induced cocaine-seeking behavior. However, prolonged loss of lOFC output enhances the motivational salience of cocaine-paired contextual stimuli likely by eliciting compensatory neuroadaptations, with the effects of post-training lOFC lesions reflecting an intermediate state of compensatory neuroplasticity. Overall, these findings support the idea that OFC dysfunction may promote cue reactivity and enhance relapse propensity in cocaine users. PMID:19769591

Low Striatal Dopamine D2-type Receptor Availability is Linked to Simulated Drug Choice in Methamphetamine Users.

PubMed

Moeller, Scott J; Okita, Kyoji; Robertson, Chelsea L; Ballard, Michael E; Konova, Anna B; Goldstein, Rita Z; Mandelkern, Mark A; London, Edythe D

2018-03-01

Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related vs affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BP ND ) for [ 18 F]fallypride. Thirteen of the methamphetamine users and 10 controls also underwent [ 11 C]NNC112 PET scans to measure dopamine D1-type receptor availability. Group analyses showed that, compared with controls, methamphetamine users chose to view more methamphetamine-related images on one task, with a similar trend on the second task. Regression analyses showed that, on both tasks, the more methamphetamine users chose to view methamphetamine images, specifically vs pleasant images (the most frequently chosen images across all participants), the lower was their D2-type BP ND in the lateral orbitofrontal cortex, an important region in value-based choice. No associations were observed with D2-type BP ND in striatal regions, or with D1-type BP ND in any region. These results identify a neurochemical correlate for a laboratory drug-seeking paradigm that can be administered to treatment-seeking and abstaining drug-addicted individuals. More broadly, these results refine the central hypothesis that dopamine-system deficits contribute to drug-biased decision-making in addiction, here showing a role for the orbitofrontal cortex.

Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals' ability to alter decision-making behavior after reinforcer devaluation.

PubMed

Zeeb, Fiona D; Winstanley, Catharine A

2013-04-10

An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.

Successful pharmacotherapy for the treatment of severe feeding aversion with mechanistic insights from cross-species neuronal remodeling

PubMed Central

Sharp, W G; Allen, A G; Stubbs, K H; Criado, K K; Sanders, R; McCracken, C E; Parsons, R G; Scahill, L; Gourley, S L

2017-01-01

Pediatric feeding disorders affect up to 5% of children, causing severe food intake problems that can result in serious medical and developmental outcomes. Behavioral intervention (BI) is effective in extinguishing feeding aversions, and also expert-dependent, time/labor-intensive and not well understood at a neurobiological level. Here we first conducted a double-blind, placebo-controlled trial comparing BI with BI plus d-cycloserine (DCS). DCS is a partial N-methyl-d-aspartate (NMDA) receptor agonist shown to augment extinction therapies in multiple anxiety disorders. We examined whether DCS enhanced extinction of feeding aversion in 15 children with avoidant/restrictive food intake disorder (ages 20–58 months). After five treatment days, BI improved feeding by 37%. By contrast, BI+DCS improved feeding by 76%. To gain insight into possible mechanisms of successful intervention, we next tested the neurobiological consequences of DCS in a murine model of feeding aversion and avoidance. In mice with conditioned food aversion, DCS enhanced avoidance extinction across a broad dose range. Confocal fluorescence microscopy and three-dimensional neuronal reconstruction indicated that DCS enlarged dendritic spine heads—the primary sites of excitatory plasticity in the brain—within the orbitofrontal prefrontal cortex, a sensory-cognition integration hub. DCS also increased phosphorylation of the plasticity-associated extracellular signal-regulated kinase 1/2. In summary, DCS successfully augments the extinction of food aversion in children and mice, an effect that may involve plasticity in the orbitofrontal cortex. These results warrant a larger-scale efficacy study of DCS for the treatment of pediatric feeding disorders and further investigations of neural mechanisms. PMID:28632204

Orbitofrontal cortex and drug use during adolescence: role of prenatal exposure to maternal smoking and BDNF genotype.

PubMed

Lotfipour, Shahrdad; Ferguson, Eamonn; Leonard, Gabriel; Perron, Michel; Pike, Bruce; Richer, Louis; Séguin, Jean R; Toro, Roberto; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomás

2009-11-01

Prenatal exposure to maternal cigarette smoking (PEMCS) may affect brain development and behavior in adolescent offspring. To evaluate the involvement of the orbitofrontal cortex (OFC) in mediating the relationship between PEMCS and substance use. Cross-sectional analyses from the Saguenay Youth Study aimed at evaluating the effects of PEMCS on brain development and behavior among adolescents. Nonexposed adolescents were matched with adolescents exposed prenatally to cigarette smoking by maternal educational level. A French Canadian founder population of the Saguenay-Lac-Saint-Jean region of Quebec, Canada. The behavioral data set included 597 adolescents (275 sibships; 12-18 years of age), half of whom were exposed in utero to maternal cigarette smoking. Analysis of cortical thickness and genotyping were performed using available data from 314 adolescents. The likelihood of substance use was assessed with the Diagnostic Interview Schedule for Children Predictive Scales. The number of different drugs tried by each adolescent was assessed using another questionnaire. Thickness of the OFC was estimated from T1-weighted magnetic resonance images using FreeSurfer software. Prenatal exposure to maternal cigarette smoking is associated with an increased likelihood of substance use. Among exposed adolescents, the likelihood of drug experimentation correlates with the degree of OFC thinning. In nonexposed adolescents, the thickness of the OFC increases as a function of the number of drugs tried. The latter effect is moderated by a brain-derived neurotrophic factor (BDNF) genotype (Val66Met). We speculate that PEMCS interferes with the development of the OFC and, in turn, increases the likelihood of drug use among adolescents. In contrast, we suggest that, among nonexposed adolescents, drug experimentation influences the OFC thickness via processes akin to experience-induced plasticity.

Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

PubMed

Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

2015-01-28

Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.

Paralimbic system and striatum are involved in motivational behavior.

PubMed

Nishimura, Masahiko; Yoshii, Yoshihiko; Watanabe, Jobu; Ishiuchi, Shogo

2009-10-28

Goal-directed rewarded behavior and goal-directed non-rewarded behavior are concerned with motivation. However, the neural substrates involved in goal-directed non-rewarded behaviors are unknown. Using functional magnetic resonance imaging, we investigated the brain activities of healthy individuals during a novel tool use (turning a screwdriver) to elucidate the relationship between the brain mechanism relevant to goal-directed non-rewarded behavior and motivation. We found that our designed behavioral task evoked activities in the orbitofrontal cortex, striatum, anterior insula, lateral prefrontal cortex, and anterior cingulate cortex compared with a meaningless task. These results suggest that activation in these cerebral regions play important roles in motivational behavior without tangible rewards.

Reward system and temporal pole contributions to affective evaluation during a first person shooter video game.

PubMed

Mathiak, Krystyna A; Klasen, Martin; Weber, René; Ackermann, Hermann; Shergill, Sukhwinder S; Mathiak, Klaus

2011-07-12

Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI) with individual affect measures to address the neuronal correlates of violence in a video game. Thirteen male German volunteers played a first-person shooter game (Tactical Ops: Assault on Terror) during fMRI measurement. We defined success as eliminating opponents, and failure as being eliminated themselves. Affect was measured directly before and after game play using the Positive and Negative Affect Schedule (PANAS). Failure and success events evoked increased activity in visual cortex but only failure decreased activity in orbitofrontal cortex and caudate nucleus. A negative correlation between negative affect and responses to failure was evident in the right temporal pole (rTP). The deactivation of the caudate nucleus during failure is in accordance with its role in reward-prediction error: it occurred whenever subject missed an expected reward (being eliminated rather than eliminating the opponent). We found no indication that violence events were directly rewarding for the players. We addressed subjective evaluations of affect change due to gameplay to study the reward system. Subjects reporting greater negative affect after playing the game had less rTP activity associated with failure. The rTP may therefore be involved in evaluating the failure events in a social context, to regulate the players' mood.

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

PubMed Central

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

2013-01-01

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

Separate and overlapping brain areas encode subjective value during delay and effort discounting.

PubMed

Massar, Stijn A A; Libedinsky, Camilo; Weiyan, Chee; Huettel, Scott A; Chee, Michael W L

2015-10-15

Making decisions about rewards that involve delay or effort requires the integration of value and cost information. The brain areas recruited in this integration have been well characterized for delay discounting. However only a few studies have investigated how effort costs are integrated into value signals to eventually determine choice. In contrast to previous studies that have evaluated fMRI signals related to physical effort, we used a task that focused on cognitive effort. Participants discounted the value of delayed and effortful rewards. The value of cognitively effortful rewards was represented in the anterior portion of the inferior frontal gyrus and dorsolateral prefrontal cortex. Additionally, the value of the chosen option was encoded in the anterior cingulate cortex, caudate, and cerebellum. While most brain regions showed no significant dissociation between effort discounting and delay discounting, the ACC was significantly more activated in effort compared to delay discounting tasks. Finally, overlapping regions within the right orbitofrontal cortex and lateral temporal and parietal cortices encoded the value of the chosen option during both delay and effort discounting tasks. These results indicate that encoding of rewards discounted by cognitive effort and delay involves partially dissociable brain areas, but a common representation of chosen value is present in the orbitofrontal, temporal and parietal cortices. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Examining brain structures associated with the motive to achieve success and the motive to avoid failure: A voxel-based morphometry study.

PubMed

Ming, Dan; Chen, Qunlin; Yang, Wenjing; Chen, Rui; Wei, Dongtao; Li, Wenfu; Qiu, Jiang; Xu, Zhan; Zhang, Qinglin

2016-01-01

The motive to achieve success (MAS) and motive to avoid failure (MAF) are two different but classical kinds of achievement motivation. Though many functional magnetic resonance imaging studies have explored functional activation in motivation-related conditions, research has been silent as to the brain structures associated with individual differences in achievement motivation, especially with respect to MAS and MAF. In this study, the voxel-based morphometry method was used to uncover focal differences in brain structures related to MAS and MAF measured by the Mehrabian Achieving Tendency Scale in 353 healthy young Chinese adults. The results showed that the brain structures associated with individual differences in MAS and MAF were distinct. MAS was negatively correlated with regional gray matter volume (rGMV) in the medial prefrontal cortex (mPFC)/orbitofrontal cortex while MAF was negatively correlated with rGMV in the mPFC/subgenual cingulate gyrus. After controlling for mutual influences of MAS and MAF scores, MAS scores were found to be related to rGMV in the mPFC/orbitofrontal cortex and another cluster containing the parahippocampal gyrus and precuneus. These results may predict that compared with MAF, the generation process of MAS may be more complex and rational, thus in the real world, perhaps MAS is more beneficial to personal growth and guaranteeing the quality of task performance.

Behavioural and brain responses related to Internet search and memory.

PubMed

Dong, Guangheng; Potenza, Marc N

2015-10-01

The ready availability of data via searches on the Internet has changed how many people seek and perhaps store and recall information, although the brain mechanisms underlying these processes are not well understood. This study investigated brain mechanisms underlying Internet-based vs. non-Internet-based searching. The results showed that Internet searching was associated with lower accuracy in recalling information as compared with traditional book searching. During functional magnetic resonance imaging, Internet searching was associated with less regional brain activation in the left ventral stream, the association area of the temporal-parietal-occipital cortices, and the middle frontal cortex. When comparing novel items with remembered trials, Internet-based searching was associated with higher brain activation in the right orbitofrontal cortex and lower brain activation in the right middle temporal gyrus when facing those novel trials. Brain activations in the middle temporal gyrus were inversely correlated with response times, and brain activations in the orbitofrontal cortex were positively correlated with self-reported search impulses. Taken together, the results suggest that, although Internet-based searching may have facilitated the information-acquisition process, this process may have been performed more hastily and be more prone to difficulties in recollection. In addition, people appear less confident in recalling information learned through Internet searching and that recent Internet searching may promote motivation to use the Internet. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex.

PubMed

Yates, J R; Darna, M; Beckmann, J S; Dwoskin, L P; Bardo, M T

2016-01-28

Impulsivity, which can be subdivided into impulsive action and impulsive choice, is implicated as a factor underlying drug abuse vulnerability. Although previous research has shown that dopamine (DA) systems in prefrontal cortex are involved in impulsivity and substance abuse, it is not known if inherent variation in DA transporter (DAT) function contributes to impulsivity. The current study determined if individual differences in either impulsive action or impulsive choice are related to DAT function in orbitofrontal (OFC) and/or medial prefrontal cortex (mPFC). Rats were first tested both for impulsive action in a cued go/no-go task and for impulsive choice in a delay-discounting task. Following behavioral evaluation, in vitro [(3)H]DA uptake assays were performed in OFC and mPFC isolated from individual rats. Vmax in OFC, but not mPFC, was correlated with performance in the cued go/no-go task, with decreased OFC DAT function being associated with high impulsive action. In contrast, Vmax in OFC and mPFC was not correlated with performance in the delay-discounting task. The current results demonstrate that impulsive behavior in cued go/no-go performance is associated with decreased DAT function in OFC, suggesting that hyperdopaminergic tone in this prefrontal subregion mediates, at least in part, increased impulsive action. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization.

PubMed

Fera, Francesco; Passamonti, Luca; Herzallah, Mohammad M; Myers, Catherine E; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A

2014-07-01

To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Copyright © 2013 Wiley Periodicals, Inc.

Neural processing of reward and punishment in young people at increased familial risk of depression.

PubMed

McCabe, Ciara; Woffindale, Caroline; Harmer, Catherine J; Cowen, Philip J

2012-10-01

Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16-21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers.

PubMed

Fishbein, Diana H; Eldreth, Diana L; Hyde, Christopher; Matochik, John A; London, Edythe D; Contoreggi, Carlo; Kurian, Varughese; Kimes, Alane S; Breeden, Andrew; Grant, Steven

2005-04-01

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.

Parcellation of the human orbitofrontal cortex based on gray matter volume covariance.

PubMed

Liu, Huaigui; Qin, Wen; Qi, Haotian; Jiang, Tianzi; Yu, Chunshui

2015-02-01

The human orbitofrontal cortex (OFC) is an enigmatic brain region that cannot be parcellated reliably using diffusional and functional magnetic resonance imaging (fMRI) because there is signal dropout that results from an inherent defect in imaging techniques. We hypothesise that the OFC can be reliably parcellated into subregions based on gray matter volume (GMV) covariance patterns that are derived from artefact-free structural images. A total of 321 healthy young subjects were examined by high-resolution structural MRI. The OFC was parcellated into subregions-based GMV covariance patterns; and then sex and laterality differences in GMV covariance pattern of each OFC subregion were compared. The human OFC was parcellated into the anterior (OFCa), medial (OFCm), posterior (OFCp), intermediate (OFCi), and lateral (OFCl) subregions. This parcellation scheme was validated by the same analyses of the left OFC and the bilateral OFCs in male and female subjects. Both visual observation and quantitative comparisons indicated a unique GMV covariance pattern for each OFC subregion. These OFC subregions mainly covaried with the prefrontal and temporal cortices, cingulate cortex and amygdala. In addition, GMV correlations of most OFC subregions were similar across sex and laterality except for significant laterality difference in the OFCl. The right OFCl had stronger GMV correlation with the right inferior frontal cortex. Using high-resolution structural images, we established a reliable parcellation scheme for the human OFC, which may provide an in vivo guide for subregion-level studies of this region and improve our understanding of the human OFC at subregional levels. © 2014 Wiley Periodicals, Inc.

UNCINATE FASCICULUS FRACTIONAL ANISOTROPY CORRELATES WITH TYPICAL USE OF REAPPRAISAL IN WOMEN BUT NOT MEN

PubMed Central

Zuurbier, Lisette A.; Nikolova, Yuliya S.; Ahs, Fredrik; Hariri, Ahmad R.

2014-01-01

Emotion regulation refers to strategies through which individuals influence their experience and expression of emotions. Two typical strategies are reappraisal, a cognitive strategy for reframing the context of an emotional experience, and suppression, a behavioral strategy for inhibiting emotional responses. Functional neuroimaging studies have revealed that regions of the prefrontal cortex modulate amygdala reactivity during both strategies, but relatively greater down-regulation of the amygdala occurs during reappraisal. Moreover, these studies demonstrated that engagement of this modulatory circuitry varies as a function of gender. The uncinate fasciculus is a major structural pathway connecting regions of the anterior temporal lobe, including the amygdala, to inferior frontal regions, especially the orbitofrontal cortex. The objective of the current study was to map variability in the structural integrity of the uncinate fasciculus onto individual differences in self-reported typical use of reappraisal and suppression. Diffusion tensor imaging was used in 194 young adults to derive regional fractional anisotropy values for the right and left uncinate fasciculus. All participants also completed the Emotion Regulation Questionnaire. In women but not men, self-reported typical reappraisal use was positively correlated with fractional anisotropy values in a region of the left uncinate fasciculus within the orbitofrontal cortex. In contrast, typical use of suppression was not significantly correlated with fractional anisotropy in any region of the uncinate fasciculus in either men or women. Our data suggest that in women typical reappraisal use is specifically related to the integrity of white matter pathways linking the amygdala and prefrontal cortex. PMID:23398586

Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study.

PubMed

Dickstein, Daniel P; Milham, Michael P; Nugent, Allison C; Drevets, Wayne C; Charney, Dennis S; Pine, Daniel S; Leibenluft, Ellen

2005-07-01

While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. Ongoing study of the pathophysiology of pediatric BPD. Intramural National Institute of Mental Health; approved by the institutional review board. Patients Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD.

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

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making.

PubMed

Khani, Abbas; Kermani, Mojtaba; Hesam, Soghra; Haghparast, Abbas; Argandoña, Enrike G; Rainer, Gregor

2015-06-01

Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during cost-benefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

The GABAergic Anterior Paired Lateral Neurons Facilitate Olfactory Reversal Learning in "Drosophila"

ERIC Educational Resources Information Center

Wu, Yanying; Ren, Qingzhong; Li, Hao; Guo, Aike

2012-01-01

Reversal learning has been widely used to probe the implementation of cognitive flexibility in the brain. Previous studies in monkeys identified an essential role of the orbitofrontal cortex (OFC) in reversal learning. However, the underlying circuits and molecular mechanisms are poorly understood. Here, we use the T-maze to investigate the neural…

Updating existing emotional memories involves the frontopolar/orbitofrontal cortex in ways that acquiring new emotional memories does not

PubMed Central

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2011-01-01

In life, we must often learn new associations to people, places, or things we already know. The current functional magnetic resonance imaging study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location associations for old pictures (i.e., pictures previously associated with other neutral stimuli) and new pictures (i.e., pictures not seen in the first phase). There was greater frontopolar/ orbitofrontal (OFC) activity when people learned picture-location associations for old negative pictures than for new negative pictures, but frontopolar OFC activity did not significantly differ during learning locations of old versus new neutral pictures. In addition, frontopolar activity was more negatively correlated with the amygdala when participants learned picture-location associations for old negative pictures than for new negative or old neutral pictures. Past studies revealed that the frontopolar OFC allows for updating the affective values of stimuli in reversal learning or extinction of conditioning (e.g., Izquierdo & Murray, 2005); our findings suggest that it plays a more general role in updating associations to emotional stimuli. PMID:21568639

Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering

PubMed Central

Sitek, Kevin R.; Cai, Shanqing; Beal, Deryk S.; Perkell, Joseph S.; Guenther, Frank H.; Ghosh, Satrajit S.

2016-01-01

Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers. PMID:27199712

Pathways for Emotions: Specializations in the Amygdalar, Mediodorsal Thalamic, and Posterior Orbitofrontal Network.

PubMed

Timbie, Clare; Barbas, Helen

2015-08-26

The primate amygdala projects to posterior orbitofrontal cortex (pOFC) directly and possibly indirectly through a pathway to the magnocellular mediodorsal thalamic nucleus (MDmc), which may convey signals about the significance of stimuli. However, because MDmc receives input from structures in addition to the amygdala and MDmc projects to areas in addition to pOFC, it is unknown whether amygdalar pathways in MDmc innervate pOFC-bound neurons. We addressed this issue using double- or triple-labeling approaches to identify pathways and key cellular and molecular features in rhesus monkeys. We found that amygdalar terminations innervated labeled neurons in MDmc that project to pOFC. Projection neurons in MDmc directed to pOFC included comparatively fewer "core" parvalbumin neurons that project focally to the middle cortical layers and more "matrix" calbindin neurons that project expansively to the upper cortical layers. In addition, a small and hitherto unknown pathway originated from MDmc calretinin neurons and projected to pOFC. Further, whereas projection neurons directed to MDmc and to pOFC were intermingled in the amygdala, none projected to both structures. Larger amygdalar neurons projected to MDmc and expressed the vesicular glutamate transporter 2 (VGLUT2), which is found in highly efficient "driver" pathways. In contrast, smaller amygdalar neurons directed to pOFC expressed VGLUT1 found in modulatory pathways. The indirect pathway from the amygdala to pOFC via MDmc may provide information about the emotional significance of events and, along with a parallel direct pathway, ensures transfer of signals to all layers of pOFC. The amygdala-the brain's center for emotions-is strongly linked with the orbital cortex, a region associated with social interactions. This study provides evidence that a robust pathway from the amygdala reaches neurons in the thalamus that link directly with the orbital cortex, forming a tight tripartite network. The dual pathways from the amygdala to the orbital cortex and to the thalamus are distinct by morphology, neurochemistry, and function. This tightly linked network suggests the presence of fool-proof avenues for emotions to influence high-order cortical areas associated with affective reasoning. Specific nodes of this tripartite network are disrupted in psychiatric diseases, divorcing areas that integrate emotions and thoughts for decisions and flexible behavior. Copyright © 2015 the authors 0270-6474/15/3511976-12$15.00/0.

Depression in chronic ketamine users: Sex differences and neural bases.

PubMed

Li, Chiang-Shan R; Zhang, Sheng; Hung, Chia-Chun; Chen, Chun-Ming; Duann, Jeng-Ren; Lin, Ching-Po; Lee, Tony Szu-Hsien

2017-11-30

Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users. Copyright © 2017 Elsevier B.V. All rights reserved.

How demanding is the brain on a reversal task under day and night conditions?

PubMed

Arias, N; Fidalgo, C; Méndez, M; Arias, J L

2015-07-23

Reversal learning has been studied as the process of learning to inhibit previously rewarded actions. These behavioral studies are usually performed during the day, when animals are in their daily period rest. However, how day or night affects spatial reversal learning and the brain regions involved in the learning process are still unknown. We conducted two experiments using the Morris Water Maze under different light-conditions: naïve group (CN, n=8), day group (DY, n=8), control DY group (CDY, n=8) night group (NG, n=8), and control NG group (CNG, n=7). Distance covered, velocity and latencies to reach the platform were examined. After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. There were no behavioral differences in the time of day when the animals were trained. However, the metabolic brain consumption was higher in rats trained in the day condition. This CO increase was supported by the prefrontal cortex, thalamus, dorsal and ventral striatum, hippocampus and entorhinal cortex, revealing their role in the performance of the spatial reversal learning task. Finally, the orbitofrontal cortex has been revealed as a key structure in reversal learning execution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The neural basis of implicit moral attitude--an IAT study using event-related fMRI.

PubMed

Luo, Qian; Nakic, Marina; Wheatley, Thalia; Richell, Rebecca; Martin, Alex; Blair, R James R

2006-05-01

Recent models of morality have suggested the importance of affect-based automatic moral attitudes in moral reasoning. However, previous investigations of moral reasoning have frequently relied upon explicit measures that are susceptible to voluntary control. To investigate participant's automatic moral attitudes, we used a morality Implicit Association Test (IAT). Participants rated the legality of visually depicted legal and illegal behaviors of two different intensity levels (e.g., high intensity illegal = interpersonal violence; low intensity illegal = vandalism) both when the target concept (e.g., illegal) was behaviorally paired with an associated attribute (e.g., bad; congruent condition) or an unassociated attribute (e.g., good; incongruent condition). Behaviorally, an IAT effect was shown; RTs were faster in the congruent rather than incongruent conditions. At the neural level, implicit moral attitude, as indexed by increased BOLD response as a function of stimulus intensity, was associated with increased activation in the right amygdala and the ventromedial orbitofrontal cortex. In addition, performance on incongruent trials relative to congruent trials was associated with increased activity in the right ventrolateral prefrontal cortex (BA 47), left subgenual cingulate gyrus (BA 25), bilateral premotor cortex (BA 6) and the left caudate. The functional contributions of these regions in moral reasoning are discussed.

Transcranial Direct Current Stimulation Improves Executive Dysfunctions in ADHD: Implications for Inhibitory Control, Interference Control, Working Memory, and Cognitive Flexibility.

PubMed

Nejati, Vahid; Salehinejad, Mohammad Ali; Nitsche, Michael A; Najian, Asal; Javadi, Amir-Homayoun

2017-09-01

This study examined effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) on major executive functions (EFs), including response inhibition, executive control, working memory (WM), and cognitive flexibility/task switching in ADHD. ADHD children received (a) left anodal/right cathodal DLPFC tDCS and (b) sham stimulation in Experiment 1 and (a) left anodal DLPFC/right cathodal OFC tDCS, (b) left cathodal DLPFC/right anodal OFC tDCS, and (c) sham stimulation in Experiment 2. The current intensity was 1 mA for 15 min with a 72-hr interval between sessions. Participants underwent Go/No-Go task, N-back test, Wisconsin Card Sorting Test (WCST), and Stroop task after each tDCS condition. Anodal left DLPFC tDCS most clearly affected executive control functions (e.g., WM, interference inhibition), while cathodal left DLPFC tDCS improved inhibitory control. Cognitive flexibility/task switching benefited from combined DLPFC-OFC, but not DLPFC stimulation alone. Task-specific stimulation protocols can improve EFs in ADHD.

The Neural Basis of Contextual Influences on Face Categorization

PubMed Central

Freeman, Jonathan B.; Ma, Yina; Barth, Maria; Young, Steven G.; Han, Shihui; Ambady, Nalini

2015-01-01

From only brief exposure to a face, individuals spontaneously categorize another's race. Recent behavioral evidence suggests that visual context may affect such categorizations. We used fMRI to examine the neural basis of contextual influences on the race categorization of faces. Participants categorized the race of faces that varied along a White-Asian morph continuum and were surrounded by American, neutral, or Chinese scene contexts. As expected, the context systematically influenced categorization responses and their efficiency (response times). Neuroimaging results indicated that the retrosplenial cortex (RSC) and orbitofrontal cortex (OFC) exhibited highly sensitive, graded responses to the compatibility of facial and contextual cues. These regions showed linearly increasing responses as a face became more White when in an American context, and linearly increasing responses as a face became more Asian when in a Chinese context. Further, RSC activity partially mediated the effect of this face-context compatibility on the efficiency of categorization responses. Together, the findings suggest a critical role of the RSC and OFC in driving contextual influences on face categorization, and highlight the impact of extraneous cues beyond the face in categorizing other people. PMID:24006403

Specializations for reward-guided decision-making in the primate ventral prefrontal cortex.

PubMed

Murray, Elisabeth A; Rudebeck, Peter H

2018-05-23

The estimated values of choices, and therefore decision-making based on those values, are influenced by both the chance that the chosen items or goods can be obtained (availability) and their current worth (desirability) as well as by the ability to link the estimated values to choices (a process sometimes called credit assignment). In primates, the prefrontal cortex (PFC) has been thought to contribute to each of these processes; however, causal relationships between particular subdivisions of the PFC and specific functions have been difficult to establish. Recent lesion-based research studies have defined the roles of two different parts of the primate PFC - the orbitofrontal cortex (OFC) and the ventral lateral frontal cortex (VLFC) - and their subdivisions in evaluating each of these factors and in mediating credit assignment during reward-based decision-making.

A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

PubMed Central

Logotheti, Marianthi; Papadodima, Olga; Venizelos, Nikolaos; Chatziioannou, Aristotelis; Kolisis, Fragiskos

2013-01-01

Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets. PMID:23554570

Rhythmic ictal nonclonic hand (RINCH) motions in temporal lobe epilepsy: invasive EEG findings, incidence, and lateralizing value.

PubMed

Kuba, Robert; Musilová, Klára; Vojvodič, Nikola; Tyrlíková, Ivana; Rektor, Ivan; Brázdil, Milan

2013-10-01

The main purpose of this retrospective analysis was to evaluate the incidence and lateralization value of rhythmic ictal nonclonic hand (RINCH) motions in patients with temporal lobe epilepsy (TLE), who were classified as Engel I at least 2 years after epilepsy surgery. We analyzed the distribution of ictal activity at the time of RINCH appearance in patients in whom RINCH motions were present during invasive EEG monitoring. A group of 120 patients was included in this study. In total, we reviewed 491 seizures: 277 seizures in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (TLE-HS group) and 214 in TLE caused by other lesions (TLE-OTH group). We analyzed 29 patients (79 of the seizures) during invasive EEG monitoring. Fisher's exact test and binomial test were used for the statistical analysis. RINCH motions were observed in 24 out of 120 patients (20%) and in 48 out of 491 seizures (9.8%). There was no significant difference between the occurrence of RINCH motions in patients with TLE-HS and in patients with TLE-OTH, or between gender, right/left-sided TLE, and language dominant/nondominant TLE. RINCH motions were contralateral to the seizure onset in 83.3% of patients and 91.7% of seizures (p=0.0015; p<0.001, respectively). There were no differences in the lateralizing value of RINCH motions in patients with TLE-HS or TLE-OTH. We analyzed RINCH motions in 5 patients/7 seizures during invasive EEG. In all 7 seizures with RINCH motions, we observed the widespread activation of the temporal lobe (mesial and lateral, opercular and polar regions) contralateral to the side of RINCH motions. In all 7 seizures, we observed that at the time of RINCH motion onset, at least 1 explored region of the frontal lobe was affected by the ictal activity. In 3 seizures, we observed time-locked epileptic activation associated with the appearance of RINCH motions, i.e., in the orbitofrontal cortex in 2 seizures and in both the orbitofrontal cortex and anterior cingulate gyrus in 1 seizure. RINCH motions are a relatively frequent ictal sign in patients with TLE. They have a high lateralizing value in these patients, occurring contralateral to the ictal onset. RINCH motions usually occur after the spread of ictal activity beyond the temporal lobe, and their appearance is usually associated with the presence of ictal activity in various regions of the contralateral frontal lobe, mainly the orbitofrontal cortex and anterior cingulate gyrus. This is the first study analysing this phenomenon during invasive EEG recording. Copyright © 2013 Elsevier B.V. All rights reserved.

Intimate stimuli result in fronto-parietal activation changes in anorexia nervosa.

PubMed

van Zutphen, L; Maier, S; Siep, N; Jacob, G A; Tüscher, O; van Elst, L Tebartz; Zeeck, A; Arntz, A; O'Connor, M-F; Stamm, H; Hudek, M; Joos, Andreas

2018-02-03

Intimacy is a key psychological problem in anorexia nervosa (AN). Empirical evidence, including neurobiological underpinnings, is however, scarce. In this study, we evaluated various emotional stimuli including intimate stimuli experienced in patients with AN and non-patients, as well as their cerebral response. Functional magnetic resonance imaging was conducted using stimuli with positive, neutral, negative and intimate content. Participants (14 AN patients and 14 non-patients) alternated between passive viewing and explicit emotion regulation. Intimate stimuli were experienced less positively in AN patients compared to non-patients. AN patients showed decreased cerebral responses in superior parietal cortices in response to positive and intimate stimuli. Intimate stimuli led to stronger activation of the orbitofrontal cortex, and lower activation of the bilateral precuneus in AN patients. Orbitofrontal responses decreased in AN patients during explicit emotion regulation. These results show that intimate stimuli are of particular importance in AN patients, who show experiential differences compared to non-patients and altered activation of orbitofrontal and parietal brain structures. This supports that AN patients have difficulties with intimacy, attachment, self-referential processing and body perception. Level III, case-control study.

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.

Prolonged hemodynamic response during incidental facial emotion processing in inter-episode bipolar I disorder.

PubMed

Rosenfeld, Ethan S; Pearlson, Godfrey D; Sweeney, John A; Tamminga, Carol A; Keshavan, Matcheri S; Nonterah, Camilla; Stevens, Michael C

2014-03-01

This fMRI study examined whether hemodynamic responses to affectively-salient stimuli were abnormally prolonged in remitted bipolar disorder, possibly representing a novel illness biomarker. A group of 18 DSM-IV bipolar I-diagnosed adults in remission and a demographically-matched control group performed an event-related fMRI gender-discrimination task in which face stimuli had task-irrelevant neutral, happy or angry expressions designed to elicit incidental emotional processing. Participants' brain activation was modeled using a "fully informed" SPM5 basis set. Mixed-model ANOVA tested for diagnostic group differences in BOLD response amplitude and shape within brain regions-of-interest selected from ALE meta-analysis of previous comparable fMRI studies. Bipolar-diagnosed patients had a generally longer duration and/or later-peaking hemodynamic response in amygdala and numerous prefrontal cortex brain regions. Data are consistent with existing models of bipolar limbic hyperactivity, but the prolonged frontolimbic response more precisely details abnormalities recognized in previous studies. Prolonged hemodynamic responses were unrelated to stimulus type, task performance, or degree of residual mood symptoms, suggesting an important novel trait vulnerability brain dysfunction in bipolar disorder. Bipolar patients also failed to engage pregenual cingulate and left orbitofrontal cortex-regions important to models of automatic emotion regulation-while engaging a delayed dorsolateral prefrontal cortex response not seen in controls. These results raise questions about whether there are meaningful relationships between bipolar dysfunction of specific ventromedial prefrontal cortex regions believed to automatically regulate emotional reactions and the prolonged responses in more lateral aspects of prefrontal cortex.

Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions.

PubMed

Wiech, K; Jbabdi, S; Lin, C S; Andersson, J; Tracey, I

2014-10-01

Functional neuroimaging studies suggest that the anterior, mid, and posterior division of the insula subserve different functions in the perception of pain. The anterior insula (AI) has predominantly been associated with cognitive-affective aspects of pain, while the mid and posterior divisions have been implicated in sensory-discriminative processing. We examined whether this functional segregation is paralleled by differences in (1) structural and (2) resting state connectivity and (3) in correlations with pain-relevant psychological traits. Analyses were restricted to the 3 insular subdivisions and other pain-related brain regions. Both type of analyses revealed largely overlapping results. The AI division was predominantly connected to the ventrolateral prefrontal cortex (structural and resting state connectivity) and orbitofrontal cortex (structural connectivity). In contrast, the posterior insula showed strong connections to the primary somatosensory cortex (SI; structural connectivity) and secondary somatosensory cortex (SII; structural and resting state connectivity). The mid insula displayed a hybrid connectivity pattern with strong connections with the ventrolateral prefrontal cortex, SII (structural and resting state connectivity) and SI (structural connectivity). Moreover, resting state connectivity revealed strong connectivity of all 3 subdivisions with the thalamus. On the behavioural level, AI structural connectivity was related to the individual degree of pain vigilance and awareness that showed a positive correlation with AI-amygdala connectivity and a negative correlation with AI-rostral anterior cingulate cortex connectivity. In sum, our findings show a differential structural and resting state connectivity for the anterior, mid, and posterior insula with other pain-relevant brain regions, which might at least partly explain their different functional profiles in pain processing. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Differential Olfactory Identification in Children with Autism and Asperger's Disorder: A Comparative and Longitudinal Study

ERIC Educational Resources Information Center

May, Tamara; Brewer, Warrick J.; Rinehart, Nicole J.; Enticott, Peter G.; Brereton, Avril V.; Tonge, Bruce J.

2011-01-01

Key theories of autism implicate orbitofrontal cortex (OFC) compromise, while olfactory identification (OI) deficits are associated with OFC dysfunction. This study aimed to complete a 5-year follow-up of children with high-functioning autism (HFA) who previously lacked the normal age-OI association; and compare unirhinal-OI in children with HFA,…

[Role of the orbitofrontal cortex in moral judgment].

PubMed

Mimura, Masaru

2010-11-01

The neural substrates of moral judgments have recently been advocated to consist of widely distributed brain networks including the orbitofrontal cortex (OFC), anterior temporal lobe and superior temporal gyrus. Moral judgments could be regarded as a conflict between the top-down rational/logical processes and the bottom-up irrational/emotional processes. Individuals with OFC damage are usually difficult to inhibit emotionally-driven outrages, thereby demonstrating severe impairment of moral judgments despite their well-preserved moral knowledge. Individuals with OFC damage frequently present with anti-social less moral behaviors. However, clinical observation indicates that some OFC patients may show "hypermoral" tendency in the sense that they are too strict to overlook other person's offense. Two representative cases with OFC damage were reported, both presented with extreme rage against others' offensive behaviors. To further elucidate the "hypermorality" of OFC patients, an experiment was performed in which patients with OFC damage and healthy control participants were asked to determine punishments for other's fictitious crimes that varied in perpetrator responsibility and crime severity. Individuals with OFC damage punished more strictly than healthy controls those persons for mitigating circumstances. The results are consistent with clinical observation of OFC patients' highly rigid and inflexible behaviors against third person's offense.

Model-based learning and the contribution of the orbitofrontal cortex to the model-free world

PubMed Central

McDannald, Michael A.; Takahashi, Yuji K.; Lopatina, Nina; Pietras, Brad W.; Jones, Josh L.; Schoenbaum, Geoffrey

2012-01-01

Learning is proposed to occur when there is a discrepancy between reward prediction and reward receipt. At least two separate systems are thought to exist: one in which predictions are proposed to be based on model-free or cached values; and another in which predictions are model-based. A basic neural circuit for model-free reinforcement learning has already been described. In the model-free circuit the ventral striatum (VS) is thought to supply a common-currency reward prediction to midbrain dopamine neurons that compute prediction errors and drive learning. In a model-based system, predictions can include more information about an expected reward, such as its sensory attributes or current, unique value. This detailed prediction allows for both behavioral flexibility and learning driven by changes in sensory features of rewards alone. Recent evidence from animal learning and human imaging suggests that, in addition to model-free information, the VS also signals model-based information. Further, there is evidence that the orbitofrontal cortex (OFC) signals model-based information. Here we review these data and suggest that the OFC provides model-based information to this traditional model-free circuitry and offer possibilities as to how this interaction might occur. PMID:22487030

Gray matter and white matter abnormalities in online game addiction.

PubMed

Weng, Chuan-Bo; Qian, Ruo-Bing; Fu, Xian-Ming; Lin, Bin; Han, Xiao-Peng; Niu, Chao-Shi; Wang, Ye-Han

2013-08-01

Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Gray Matter Loss and Related Functional Connectivity Alterations in A Chinese Family With Benign Adult Familial Myoclonic Epilepsy.

PubMed

Zeng, Ling-Li; Long, Lili; Shen, Hui; Fang, Peng; Song, Yanmin; Zhang, Linlin; Xu, Lin; Gong, Jian; Zhang, Yunci; Zhang, Yong; Xiao, Bo; Hu, Dewen

2015-10-01

Benign adult familial myoclonic epilepsy (BAFME) is a non-progressive monogenic epilepsy syndrome. So far, the structural and functional brain reorganizations in BAFME remain uncharacterized. This study aims to investigate gray matter atrophy and related functional connectivity alterations in patients with BAFME using magnetic resonance imaging (MRI).Eleven BAFME patients from a Chinese pedigree and 15 matched healthy controls were enrolled in the study. Optimized voxel-based morphometric and resting-state functional MRI approaches were performed to measure gray matter atrophy and related functional connectivity, respectively. The Trail-Making Test-part A and part B, Digit Symbol Test (DST), and Verbal Fluency Test (VFT) were carried out to evaluate attention and executive functions.The BAFME patients exhibited significant gray matter loss in the right hippocampus, right temporal pole, left orbitofrontal cortex, and left dorsolateral prefrontal cortex. With these regions selected as seeds, the voxel-wise functional connectivity analysis revealed that the right hippocampus showed significantly enhanced connectivity with the right inferior parietal lobule, bilateral middle cingulate cortex, left precuneus, and left precentral gyrus. Moreover, the BAFME patients showed significant lower scores in DST and VFT tests compared with the healthy controls. The gray matter densities of the right hippocampus, right temporal pole, and left orbitofrontal cortex were significantly positively correlated with the DST scores. In addition, the gray matter density of the right temporal pole was significantly positively correlated with the VFT scores, and the gray matter density of the right hippocampus was significantly negatively correlated with the duration of illness in the patients.The current study demonstrates gray matter loss and related functional connectivity alterations in the BAFME patients, perhaps underlying deficits in attention and executive functions in the BAFME.

Neural Mechanisms of Credit Assignment in a Multicue Environment

PubMed Central

Kolling, Nils; Brown, Joshua W.; Rushworth, Matthew

2016-01-01

In complex environments, many potential cues can guide a decision or be assigned responsibility for the outcome of the decision. We know little, however, about how humans and animals select relevant information sources that should guide behavior. We show that subjects solve this relevance selection and credit assignment problem by selecting one cue and its association with a particular outcome as the main focus of a hypothesis. To do this, we examined learning while using a task design that allowed us to estimate the focus of each subject's hypotheses on a trial-by-trial basis. When a prediction is confirmed by the outcome, then credit for the outcome is assigned to that cue rather than an alternative. Activity in medial frontal cortex is associated with the assignment of credit to the cue that is the main focus of the hypothesis. However, when the outcome disconfirms a prediction, the focus shifts between cues, and the credit for the outcome is assigned to an alternative cue. This process of reselection for credit assignment to an alternative cue is associated with lateral orbitofrontal cortex. SIGNIFICANCE STATEMENT Learners should infer which features of environments are predictive of significant events, such as rewards. This “credit assignment” problem is particularly challenging when any of several cues might be predictive. We show that human subjects solve the credit assignment problem by implicitly “hypothesizing” which cue is relevant for predicting subsequent outcomes, and then credit is assigned according to this hypothesis. This process is associated with a distinctive pattern of activity in a part of medial frontal cortex. By contrast, when unexpected outcomes occur, hypotheses are redirected toward alternative cues, and this process is associated with activity in lateral orbitofrontal cortex. PMID:26818500

How embarrassing! The behavioral and neural correlates of processing social norm violations

PubMed Central

van Steenbergen, Henk; Kreuk, Tanja; van der Wee, Nic J. A.; Westenberg, P. Michiel

2017-01-01

Social norms are important for human social interactions, and violations of these norms are evaluated partly on the intention of the actor. Here, we describe the revised Social Norm Processing Task (SNPT-R), a paradigm enabling the study of behavioral and neural responses to intended and unintended social norm violations among both adults and adolescents. We investigated how participants (adolescents and adults, n = 87) rate intentional and unintentional social norm violations with respect to inappropriateness and embarrassment, and we examined the brain activation patterns underlying the processing of these transgressions in an independent sample of 21 adults using functional Magnetic Resonance Imaging (fMRI). We hypothesized to find activation within the medial prefrontal cortex, temporo-parietal cortex and orbitofrontal cortex in response to both intentional and unintentional social norm violations, with more pronounced activation for the intentional social norm violations in these regions and in the amygdala. Participants’ ratings confirmed the hypothesis that the three types of stories are evaluated differently with respect to intentionality: intentional social norm violations were rated as the most inappropriate and most embarrassing. Furthermore, fMRI results showed that reading stories on intentional and unintentional social norm violations evoked activation within the frontal pole, the paracingulate gyrus and the superior frontal gyrus. In addition, processing unintentional social norm violations was associated with activation in, among others, the orbitofrontal cortex, middle frontal gyrus and superior parietal lobule, while reading intentional social norm violations was related to activation in the left amygdala. These regions have been previously implicated in thinking about one’s self, thinking about others and moral reasoning. Together, these findings indicate that the SNPT-R could serve as a useful paradigm for examining social norm processing, both at the behavioral and the neural level. PMID:28441460

Cortical grey matter volume reduction in people with schizophrenia is associated with neuro-inflammation

PubMed Central

Zhang, Y; Catts, V S; Sheedy, D; McCrossin, T; Kril, J J; Shannon Weickert, C

2016-01-01

Cortical grey matter volume deficits and neuro-inflammation exist in patients with schizophrenia, although it is not clear whether elevated cytokines contribute to the cortical volume reduction. We quantified cortical and regional brain volumes in fixed postmortem brains from people with schizophrenia and matched controls using stereology. Interleukin (IL)-6, IL-1β, IL-8 and SERPINA3 messenger RNAs (mRNAs) were quantified in the contralateral fresh frozen orbitofrontal cortex. We found a small, but significant reduction in cortical grey matter (1.3% F(1,85)=4.478, P=0.037) and superior frontal gyrus (6.5% F(1,80)=5.700, P=0.019) volumes in individuals with schizophrenia compared with controls. Significantly reduced cortical grey matter (9.2% F(1,24)=8.272, P=0.008) and superior frontal gyrus (13.9% F(1,20)=5.374, P=0.031) volumes were found in cases with schizophrenia and ‘high inflammation' status relative to schizophrenia cases with ‘low inflammation' status in the prefrontal cortex. The expression of inflammatory mRNAs in the orbitofrontal cortex was significantly correlated with those in dorsolateral prefrontal cortex (all r>0.417, all P<0.022), except for IL-8. Moreover, average daily and lifetime antipsychotic intake negatively correlated with cortical grey matter and superior frontal gyrus volumes (all r<−0.362, all P<0.05). The results suggest that the reduction in cortical grey matter volume in people with schizophrenia is exaggerated in those who have high expression of inflammatory cytokines. Further, antipsychotic medication intake does not appear to ameliorate the reduction in brain volume. PMID:27959331

Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

PubMed

Vaquero, Lucía; Cámara, Estela; Sampedro, Frederic; Pérez de Los Cobos, José; Batlle, Francesca; Fabregas, Josep Maria; Sales, Joan Artur; Cervantes, Mercè; Ferrer, Xavier; Lazcano, Gerardo; Rodríguez-Fornells, Antoni; Riba, Jordi

2017-05-01

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction. © 2016 Society for the Study of Addiction.

Effects of VMAT2 inhibitors lobeline and GZ-793A on methamphetamine-induced changes in dopamine release, metabolism and synthesis in vivo.

PubMed

Meyer, Andrew C; Neugebauer, Nichole M; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P; Bardo, Michael T

2013-10-01

Vesicular monoamine transporter-2 (VMAT2) inhibitors reduce methamphetamine (METH) reward in rats. The current study determined the effects of VMAT2 inhibitors lobeline (LOB; 1 or 3 mg/kg) and N-(1,2R-dihydroxylpropyl)-2,6-cis-di(4-methoxyphenethyl)piperidine hydrochloride (GZ-793A; 15 or 30 mg/kg) on METH-induced (0.5 mg/kg, SC) changes in extracellular dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in the reward-relevant nucleus accumbens (NAc) shell using in vivo microdialysis. The effect of GZ-793A (15 mg/kg) on DA synthesis in tissue also was investigated in NAc, striatum, medial prefrontal cortex and orbitofrontal cortex. In NAc shell, METH produced a time-dependent increase in extracellular DA and decrease in DOPAC. Neither LOB nor GZ-793A alone altered extracellular DA; however, both drugs increased extracellular DOPAC. In combination with METH, LOB did not alter the effects of METH on DA; however, GZ-793A, which has greater selectivity than LOB for inhibiting VMAT2, reduced the duration of the METH-induced increase in extracellular DA. Both LOB and GZ-793A enhanced the duration of the METH-induced decrease in extracellular DOPAC. METH also increased tissue DA synthesis in NAc and striatum, whereas GZ-793A decreased synthesis; no effect of METH or GZ-793A on DA synthesis was found in medial prefrontal cortex or orbitofrontal cortex. These results suggest that selective inhibition of VMAT2 produces a time-dependent decrease in DA release in NAc shell as a result of alterations in tyrosine hydroxylase activity, which may play a role in the ability of GZ-793A to decrease METH reward. © 2013 International Society for Neurochemistry.

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering.

PubMed

Kell, Christian A; Neumann, Katrin; Behrens, Marion; von Gudenberg, Alexander W; Giraud, Anne-Lise

2018-03-01

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speaking-related functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12. Copyright © 2017 Elsevier Inc. All rights reserved.

Reward system and temporal pole contributions to affective evaluation during a first person shooter video game

PubMed Central

2011-01-01

Background Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI) with individual affect measures to address the neuronal correlates of violence in a video game. Results Thirteen male German volunteers played a first-person shooter game (Tactical Ops: Assault on Terror) during fMRI measurement. We defined success as eliminating opponents, and failure as being eliminated themselves. Affect was measured directly before and after game play using the Positive and Negative Affect Schedule (PANAS). Failure and success events evoked increased activity in visual cortex but only failure decreased activity in orbitofrontal cortex and caudate nucleus. A negative correlation between negative affect and responses to failure was evident in the right temporal pole (rTP). Conclusions The deactivation of the caudate nucleus during failure is in accordance with its role in reward-prediction error: it occurred whenever subject missed an expected reward (being eliminated rather than eliminating the opponent). We found no indication that violence events were directly rewarding for the players. We addressed subjective evaluations of affect change due to gameplay to study the reward system. Subjects reporting greater negative affect after playing the game had less rTP activity associated with failure. The rTP may therefore be involved in evaluating the failure events in a social context, to regulate the players' mood. PMID:21749711

Aberrant paralimbic gray matter in criminal psychopathy.

PubMed

Ermer, Elsa; Cope, Lora M; Nyalakanti, Prashanth K; Calhoun, Vince D; Kiehl, Kent A

2012-08-01

Psychopaths impose large costs on society, as they are frequently habitual, violent criminals. The pervasive nature of emotional and behavioral symptoms in psychopathy suggests that several associated brain regions may contribute to the disorder. Studies employing a variety of methods have converged on a set of brain regions in paralimbic cortex and limbic areas that appear to be dysfunctional in psychopathy. The present study further tests this hypothesis by investigating structural abnormalities using voxel-based morphometry in a sample of incarcerated men (N=296). Psychopathy was associated with decreased regional gray matter in several paralimbic and limbic areas, including bilateral parahippocampal, amygdala, and hippocampal regions, bilateral temporal pole, posterior cingulate cortex, and orbitofrontal cortex. The consistent identification of paralimbic cortex and limbic structures in psychopathy across diverse methodologies strengthens the interpretation that these regions are crucial for understanding neural dysfunction in psychopathy. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

PubMed

Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

2015-08-01

Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments. (c) 2015 APA, all rights reserved).

Memory without context: amnesia with confabulations after infarction of the right capsular genu.

PubMed Central

Schnider, A; Gutbrod, K; Hess, C W; Schroth, G

1996-01-01

OBJECTIVE--To explore the mechanism of an amnesia marked by confabulations and lack of insight in a patient with an infarct of the right inferior capsular genu. The confabulations could mostly be traced back to earlier events, indicating that the memory disorder ensued from an inability to store the temporal and spatial context of information acquisition rather than a failure to store new information. METHODS--To test the patient's ability to store the context of information acquisition, two experiments were composed in which she was asked to decide when or where she had learned the words from two word lists presented at different points in time or in different rooms. To test her ability to store new information, two continuous recognition tests with novel non-words and nonsense designs were used. Recognition of these stimuli was assumed to be independent of the context of acquisition because the patient could not have an a priori sense of familiarity with them. RESULTS--The patient performed at chance in the experiments probing knowledge of the context of information acquisition, although she recognised the presented words almost as well as the controls. By contrast, her performance was normal in the recognition tests with non-words and nonsense designs. CONCLUSION--These findings indicate that the patient's amnesia was based on an inability to store the context of information acquisition rather than the information itself. Based on an analysis of her lesion, which disconnected the thalamus from the orbitofrontal cortex and the amygdala, and considering the similarities between her disorder, Wernicke-Korsakoff syndrome, and the amnesia after orbitofrontal lesions, it is proposed that contextual amnesia results from interruption of the loop connecting the amygdala, the dorsomedial nucleus, and the orbitofrontal cortex. Images PMID:8708688

Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N.D.; Fowler, J.; Wang, G.J.

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statisticalmore » parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.« less

Imbalanced spontaneous brain activity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression.

PubMed

Zhang, Xiaocui; Di, Xin; Lei, Hui; Yang, Juan; Xiao, Jing; Wang, Xiang; Yao, Shuqiao; Rao, Hengyi

2016-07-01

The hopelessness theory of depression posits that individuals with negative cognitive styles are at risk of developing depression following negative life events. The purpose of this work was to examine whether individuals with cognitive vulnerability to depression (CVD) exhibit similar spontaneous brain activity patterns as compared to patients with major depressive disorder (MDD). Subjects with CVD (N=32), drug-naïve first-episode patients with major depressive disorder (N=32), and sex-, age- and education-matched healthy controls (HCs; N=35) were subjected to resting state functional magnetic resonance imaging (RS-fMRI) and amplitudes of low-frequency fluctuation (ALFF) was compared between the groups. Pearson correlation analysis was performed between regional ALFFs and psychometric scores, namely the Cognitive Style Questionnaire (CSQ) and the Center for Epidemiologic Studies Depression (CES-D) scale scores. Significant group differences in ALFF values were observed bilaterally in the orbitofrontal cortex (OFC) and insular cortex (IC), and in the left fusiform gyrus (FFG). Compared to HCs, CVD subjects had reduced ALFFs in the bilateral OFC and increased ALFF in the bilateral IC and the left FFG, which were similar to the differences observed between the HCs and MDD patients. Compared to MDD patients, CVD subjects showed significant reduced ALFF values in right IC. Additionally, CSQ scores for the CVD group correlated with ALFF values in the left IC. We did not conduct a longitudinal study. Our findings were limited in cross-sectional analysis. A hypoactive OFC and hyperactive IC in a resting-state may underlie an imbalance in the spontaneous brain activity in orbitofrontal-insular circuits, and these differences may represent a trait-related marker of vulnerability to depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Neural mechanisms of risky decision-making and reward response in adolescent onset cannabis use disorder.

PubMed

De Bellis, Michael D; Wang, Lihong; Bergman, Sara R; Yaxley, Richard H; Hooper, Stephen R; Huettel, Scott A

2013-11-01

Neural mechanisms of decision-making and reward response in adolescent cannabis use disorder (CUD) are underexplored. Three groups of male adolescents were studied: CUD in full remission (n=15); controls with psychopathology without substance use disorder history (n=23); and healthy controls (n=18). We investigated neural processing of decision-making and reward under conditions of varying risk and uncertainty with the Decision-Reward Uncertainty Task while participants were scanned using functional magnetic resonance imaging. Abstinent adolescents with CUD compared to controls with psychopathology showed hyperactivation in one cluster that spanned left superior parietal lobule/left lateral occipital cortex/precuneus while making risky decisions that involved uncertainty, and hypoactivation in left orbitofrontal cortex to rewarded outcomes compared to no-reward after making risky decisions. Post hoc region of interest analyses revealed that both control groups significantly differed from the CUD group (but not from each other) during both the decision-making and reward outcome phase of the Decision-Reward Uncertainty Task. In the CUD group, orbitofrontal activations to reward significantly and negatively correlated with total number of individual drug classes the CUD patients experimented with prior to treatment. CUD duration significantly and negatively correlated with orbitofrontal activations to no-reward. The adolescent CUD group demonstrated distinctly different activation patterns during risky decision-making and reward processing (after risky decision-making) compared to both the controls with psychopathology and healthy control groups. These findings suggest that neural differences in risky decision-making and reward processes are present in adolescent addiction, persist after remission from first CUD treatment, and may contribute to vulnerability for adolescent addiction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight.

PubMed

Ganella, Eleni P; Burnett, Alice; Cheong, Jeanie; Thompson, Deanne; Roberts, Gehan; Wood, Stephen; Lee, Katherine; Duff, Julianne; Anderson, Peter J; Pantelis, Christos; Doyle, Lex W; Bartholomeusz, Cali

2015-03-01

Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (> 2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent-reported metacognition scores overall (P = 0.008) and better self-reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects. © 2014 Wiley Periodicals, Inc.

On the right side? A longitudinal study of left- versus right-lateralized semantic dementia.

PubMed

Kumfor, Fiona; Landin-Romero, Ramon; Devenney, Emma; Hutchings, Rosalind; Grasso, Roberto; Hodges, John R; Piguet, Olivier

2016-03-01

The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of individuals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimer's disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrooke's Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimer's disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimer's disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimer's disease. In addition, left semantic dementia showed greater motivation loss than Alzheimer's disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

fMRI reveals neural activity overlap between adult and infant pain

PubMed Central

Goksan, Sezgi; Hartley, Caroline; Emery, Faith; Cockrill, Naomi; Poorun, Ravi; Moultrie, Fiona; Rogers, Richard; Campbell, Jon; Sanders, Michael; Adams, Eleri; Clare, Stuart; Jenkinson, Mark; Tracey, Irene; Slater, Rebeccah

2015-01-01

Limited understanding of infant pain has led to its lack of recognition in clinical practice. While the network of brain regions that encode the affective and sensory aspects of adult pain are well described, the brain structures involved in infant nociceptive processing are less well known, meaning little can be inferred about the nature of the infant pain experience. Using fMRI we identified the network of brain regions that are active following acute noxious stimulation in newborn infants, and compared the activity to that observed in adults. Significant infant brain activity was observed in 18 of the 20 active adult brain regions but not in the infant amygdala or orbitofrontal cortex. Brain regions that encode sensory and affective components of pain are active in infants, suggesting that the infant pain experience closely resembles that seen in adults. This highlights the importance of developing effective pain management strategies in this vulnerable population. DOI: http://dx.doi.org/10.7554/eLife.06356.001 PMID:25895592

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

PubMed Central

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

2017-01-01

Abstract Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. PMID:28402565

Orbitofrontal Cortex Signals Expected Outcomes with Predictive Codes When Stable Contingencies Promote the Integration of Reward History

PubMed Central

Shapiro, Matthew L.

2017-01-01

Memory can inform goal-directed behavior by linking current opportunities to past outcomes. The orbitofrontal cortex (OFC) may guide value-based responses by integrating the history of stimulus–reward associations into expected outcomes, representations of predicted hedonic value and quality. Alternatively, the OFC may rapidly compute flexible “online” reward predictions by associating stimuli with the latest outcome. OFC neurons develop predictive codes when rats learn to associate arbitrary stimuli with outcomes, but the extent to which predictive coding depends on most recent events and the integrated history of rewards is unclear. To investigate how reward history modulates OFC activity, we recorded OFC ensembles as rats performed spatial discriminations that differed only in the number of rewarded trials between goal reversals. The firing rate of single OFC neurons distinguished identical behaviors guided by different goals. When >20 rewarded trials separated goal switches, OFC ensembles developed stable and anticorrelated population vectors that predicted overall choice accuracy and the goal selected in single trials. When <10 rewarded trials separated goal switches, OFC population vectors decorrelated rapidly after each switch, but did not develop anticorrelated firing patterns or predict choice accuracy. The results show that, whereas OFC signals respond rapidly to contingency changes, they predict choices only when reward history is relatively stable, suggesting that consecutive rewarded episodes are needed for OFC computations that integrate reward history into expected outcomes. SIGNIFICANCE STATEMENT Adapting to changing contingencies and making decisions engages the orbitofrontal cortex (OFC). Previous work shows that OFC function can either improve or impair learning depending on reward stability, suggesting that OFC guides behavior optimally when contingencies apply consistently. The mechanisms that link reward history to OFC computations remain obscure. Here, we examined OFC unit activity as rodents performed tasks controlled by contingencies that varied reward history. When contingencies were stable, OFC neurons signaled past, present, and pending events; when contingencies were unstable, past and present coding persisted, but predictive coding diminished. The results suggest that OFC mechanisms require stable contingencies across consecutive episodes to integrate reward history, represent predicted outcomes, and inform goal-directed choices. PMID:28115481

Intention Modulates the Effect of Punishment Threat in Norm Enforcement via the Lateral Orbitofrontal Cortex.

PubMed

Zhang, Yuan; Yu, Hongbo; Yin, Yunlu; Zhou, Xiaolin

2016-08-31

Although economic theories suggest that punishment threat is crucial for maintaining social norms, counterexamples are noted in which punishment threat hinders norm compliance. Such discrepancy may arise from the intention behind the threat: unintentionally introduced punishment threat facilitates, whereas intentionally introduced punishment threat hinders, norm compliance. Here, we combined a dictator game and fMRI to investigate how intention modulates the effect of punishment threat on norm compliance and the neural substrates of this modulation. We also investigated whether this modulation can be influenced by brain stimulation. Human participants divided an amount of money between themselves and a partner. The partner (intentionally) or a computer program (unintentionally) decided to retain or waive the right to punish the participant upon selfish distribution. Compared with the unintentional condition, participants allocated more when the partner intentionally waived the power of punishment, but less when the partner retained such power. The right lateral orbitofrontal cortex (rLOFC) showed higher activation when the partner waived compared with when the computer waived or when the partner retained the power. The functional connectivity between the rLOFC and the brain network associated with intention/mentalizing processing was predictive of the allocation difference induced by intention. Moreover, inhibition or activation of the rLOFC by brain stimulation decreased or increased, respectively, the participants' reliance on the partner's intention during monetary allocation. These findings demonstrate that the perceived intention of punishment threat plays a crucial role in norm compliance and that the LOFC is casually involved in the implementation of intention-based cooperative decisions. Does punishment threat facilitate or hinder norm enforcement? So far, cognitive neuroscience research offers equivocal evidence. By directly manipulating the intention behind punishment threat, we demonstrate that intention modulates the effectiveness of punishment threat. Moreover, we show that inhibition or activation of the right lateral orbitofrontal cortex (rLOFC) decreased or increased the effect of punishment threat in the intentional context, but not in the unintentional context, suggesting the casual involvement of the rLOFC in intention-based cooperative decisions. Copyright © 2016 the authors 0270-6474/16/369217-10$15.00/0.

Brain correlates of music-evoked emotions.

PubMed

Koelsch, Stefan

2014-03-01

Music is a universal feature of human societies, partly owing to its power to evoke strong emotions and influence moods. During the past decade, the investigation of the neural correlates of music-evoked emotions has been invaluable for the understanding of human emotion. Functional neuroimaging studies on music and emotion show that music can modulate activity in brain structures that are known to be crucially involved in emotion, such as the amygdala, nucleus accumbens, hypothalamus, hippocampus, insula, cingulate cortex and orbitofrontal cortex. The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders.

Regulating with imagery and the complexity of basic emotions. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Meyer, Marcel; Kuchinke, Lars

2015-06-01

Literature, music and the arts have long attested to the complexity of human emotions. Hitherto, psychological and biological theories of emotions have largely neglected this rich heritage. In their review Koelsch and colleagues [1] have embarked upon the pioneering endeavour of integrating the diverse perspectives in emotion research. Noting that the focus of prior neurobiological theories relies mainly on animal studies, the authors sought to complement this body of research with a model of complex ("moral") emotions in humans (henceforth: complex emotions). According to this novel framework, there are four main interacting affective centres in the brain. Each centre is associated with a dominant affective function, such as ascending activation (brainstem), pain/pleasure (diencephalon), attachment-related affects (hippocampus) or moral emotions and unconscious cognitive appraisal (orbitofrontal cortex). Furthermore, language is ascribed a key role in (a) the communication of subjective feeling (reconfiguration) and (b) in the conscious regulation of emotions (by means of logic and rational thought).

Gray matter alteration in isolated congenital anosmia patient: a voxel-based morphometry study.

PubMed

Yao, Linyin; Yi, Xiaoli; Wei, Yongxiang

2013-09-01

Decreased volume of gray matter (GM) was observed in olfactory loss in patients with neurodegenerative disorder. However, GM volume has not yet been investigated in isolated congenital anosmia (ICA) people. We herewith investigated the volume change of gray matter of an ICA boy by morphometric analysis of magnetic resonance images (voxel-based morphometry), and compared with that of 20 age-matched healthy controls. ICA boy presented a significant decrease in GM volume in the orbitofrontal cortex, anterior cingulate cortex, middle cingulate cortex, thalamus, insular cortex, cerebellum, precuneus, gyrus rectus, subcallosal gyrus, middle temporal gyrus, fusiform gyrus and piriform cortex. No significant GM volume increase was detected in other brain areas. The pattern of GM atrophy was similar as previous literature reported. Our results identified similar GM volume alterations regardless of the causes of olfactory impairment. Decreased GM volume was not only shown in olfactory bulbs, olfactory tracts and olfactory sulcus, also in primary olfactory cortex and the secondary cerebral olfactory areas in ICA people. This is the first study to evaluate GM volume alterations in ICA people.

Transition from 'model-based' to 'model-free' behavioral control in addiction: Involvement of the orbitofrontal cortex and dorsolateral striatum.

PubMed

Lucantonio, Federica; Caprioli, Daniele; Schoenbaum, Geoffrey

2014-01-01

Cocaine addiction is a complex and multidimensional process involving a number of behavioral and neural forms of plasticity. The behavioral transition from voluntary drug use to compulsive drug taking may be explained at the neural level by drug-induced changes in function or interaction between a flexible planning system, associated with prefrontal cortical regions, and a rigid habit system, associated with the striatum. The dichotomy between these two systems is operationalized in computational theory by positing model-based and model-free learning mechanisms, the former relying on an "internal model" of the environment and the latter on pre-computed or cached values to control behavior. In this review, we will suggest that model-free and model-based learning mechanisms appear to be differentially affected, at least in the case of psychostimulants such as cocaine, with the former being enhanced while the latter are disrupted. As a result, the behavior of long-term drug users becomes less flexible and responsive to the desirability of expected outcomes and more habitual, based on the long history of reinforcement. To support our specific proposal, we will review recent neural and behavioral evidence on the effect of psychostimulant exposure on orbitofrontal and dorsolateral striatum structure and function. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Published by Elsevier Ltd.

Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

PubMed Central

DePoy, Lauren M.; Perszyk, Riley E.; Zimmermann, Kelsey S.; Koleske, Anthony J.; Gourley, Shannon L.

2014-01-01

Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC). Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31–35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability—the p190rhogap+/– mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/– mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/– mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population. PMID:25452728

Brain magnetic resonance spectroscopy in obsessive-compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression.

PubMed

Bédard, Marie-Josée; Chantal, Sophie

2011-04-30

Brain metabolite concentrations have recently been assessed in different cerebral regions presumably targeted in patients with obsessive-compulsive disorder (OCD) using magnetic resonance spectroscopy (MRS). However, results have been divergent. Possible confounding variables, such as the cerebral localisation of investigated regions and metabolites considered, as well as subclinical symptoms of anxiety and depression, could have affected these MRS profiles. The main goal of this study was to assess MRS metabolite differences between 13 individuals with OCD and 12 matched healthy controls in seven brain regions potentially involved in OCD. The secondary objective was to assess the relationships between levels of anxiety and depression and brain metabolite concentrations. No difference was found for N-acetylaspartate, glutamate-glutamine, myo-inositol (mI) and choline relative to creatine (Cr) concentration in either the left or right orbitofrontal area, left or right median temporal lobe, left or right thalamus or the anterior cingulate cortex. A significant negative correlation between the mI/Cr in the left orbitofrontal area and the severity of OCD symptomatology was observed while subclinical anxiety and depression were closely related to brain metabolite ratios. Thus, these subclinical symptoms, commonly associated with OCD, should be considered in assessing brain metabolite concentrations and may be central to the comprehension of this disorder. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

State of expectancy modulates the neural response to visual food stimuli in humans.

PubMed

Malik, Saima; McGlone, Francis; Dagher, Alain

2011-04-01

Human brain imaging studies demonstrate distributed activation of limbic, paralimbic and sensory systems to food and food-associated cues. Activity in this circuit may be modulated by internal factors, such as hunger, and cognitive factors. Anticipation to eat is one such factor, which likely impacts consummatory behavior. Here, the neural substrates of food expectancy were identified in 10 healthy male participants who underwent two whole-brain functional Magnetic Resonance Imaging scans on separate days. Fasted subjects viewed images of food and scenery, in two counterbalanced states. During one condition, subjects were 'expecting' to eat right after the scan and during the other they were 'not expecting' to eat for 1 h after the scan. Food pictures compared with scenery yielded bilateral activation in visual areas as well as in the left insula and amygdala in both conditions. The left dorsolateral prefrontal cortex, hippocampus and putamen were additionally activated in the 'not expecting' condition while right orbitofrontal cortex activity was enhanced in the 'expecting' condition. These data suggest that cognitive manipulations affect the response to food cues in the prefrontal cortex, in areas involved in the planning and control of motivated behaviors, while the amygdala and insula responded equally in both conditions, consistent with a more basic role in homeostatically driven appetitive behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

Amygdala Functional Connectivity is Reduced After the Cold Pressor Task

PubMed Central

Clewett, David; Schoeke, Andrej; Mather, Mara

2013-01-01

The amygdala forms a crucial link between central pain and stress systems. There is much evidence that psychological stress affects amygdala activity, but it is less clear how painful stressors influence subsequent amygdala functional connectivity. In the present study, we used pulsed arterial spin labeling (PASL) to investigate differences in healthy male adults’ resting-state amygdala functional connectivity following a cold pressor versus control task, with the stressor and control conditions conducted on different days. During the period of peak cortisol response to acute stress (approximately fifteen to thirty minutes after stressor onset), participants were asked to rest for six minutes with their eyes closed during a PASL scanning sequence. The cold pressor task led to reduced resting-state functional connectivity between the amygdalae and orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC), which occurred irrespective of cortisol release. The stressor also induced greater inverse connectivity between the left amygdala and dorsal anterior cingulate cortex (dACC), a brain region implicated in the down-regulation of amygdala responsivity. Furthermore, the degree of post-stressor left amygdala decoupling with the lateral OFC varied according to self-reported pain intensity during the cold pressor task. These findings indicate that the cold pressor task alters amygdala interactions with prefrontal and ACC regions 15–30 minutes after the stressor, and that these altered functional connectivity patterns are related to pain perception rather than cortisol feedback. PMID:23645370

Long-Term Effects of Cannabis on Brain Structure

PubMed Central

Battistella, Giovanni; Fornari, Eleonora; Annoni, Jean-Marie; Chtioui, Haithem; Dao, Kim; Fabritius, Marie; Favrat, Bernard; Mall, Jean-Frédéric; Maeder, Philippe; Giroud, Christian

2014-01-01

The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich in cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study, we investigate (using Voxel-based Morphometry) gray matter changes in a group of regular cannabis smokers in comparison with a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with gray matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich in cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the 3 months before inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant gray matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger gray matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence. PMID:24633558

Long-term effects of cannabis on brain structure.

PubMed

Battistella, Giovanni; Fornari, Eleonora; Annoni, Jean-Marie; Chtioui, Haithem; Dao, Kim; Fabritius, Marie; Favrat, Bernard; Mall, Jean-Frédéric; Maeder, Philippe; Giroud, Christian

2014-08-01

The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich in cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study, we investigate (using Voxel-based Morphometry) gray matter changes in a group of regular cannabis smokers in comparison with a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with gray matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich in cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the 3 months before inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant gray matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger gray matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence.

Neural correlates of metacognitive ability and of feeling confident: a large-scale fMRI study.

PubMed

Molenberghs, Pascal; Trautwein, Fynn-Mathis; Böckler, Anne; Singer, Tania; Kanske, Philipp

2016-12-01

One important aspect of metacognition is the ability to accurately evaluate one's performance. People vary widely in their metacognitive ability and in general are too confident when evaluating their performance. This often leads to poor decision making with potentially disastrous consequences. To further our understanding of the neural underpinnings of these processes, this fMRI study investigated inter-individual differences in metacognitive ability and effects of trial-by-trial variation in subjective feelings of confidence when making metacognitive assessments. Participants (N = 308) evaluated their performance in a high-level social and cognitive reasoning task. The results showed that higher metacognitive accuracy was associated with a decrease in activation in the anterior medial prefrontal cortex, an area previously linked to metacognition on perception and memory. Moreover, the feeling of confidence about one's choices was associated with an increase of activation in reward, memory and motor related areas including bilateral striatum and hippocampus, while less confidence was associated with activation in areas linked with negative affect and uncertainty, including dorsomedial prefrontal and bilateral orbitofrontal cortex. This might indicate that positive affect is related to higher confidence thereby biasing metacognitive decisions towards overconfidence. In support, behavioural analyses revealed that increased confidence was associated with lower metacognitive accuracy. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Dysfunction of the frontolimbic region during swear word processing in young adolescents with Internet gaming disorder

PubMed Central

Chun, J-W; Choi, J; Cho, H; Lee, S-K; Kim, D J

2015-01-01

Although the Internet is an important tool in our daily life, the control of Internet use is necessary to address difficult problems. This study set out with the aim of assessing the cognitive control of affective events in Internet gaming disorder (IGD) and has examined the influence of IGD on neural activities with regard to swear words in young adolescents. We demonstrated the differences between adolescents with IGD and healthy control adolescents (HC) with respect to swear, negative and neutral word conditions. Swear words induced more activation in regions related to social interaction and emotional processing such as the superior temporal sulcus, right temporoparietal junction and orbitofrontal cortex (OFC) when compared with negative words. In this study, adolescents with IGD exhibited reduced activation in the right OFC related to cognitive control and in the dorsal anterior cingulate cortex (dACC) related to social rejection during the swear word condition. In addition, adolescents with IGD were negatively correlated with activity in the right amygdala toward swear words, indicating the important role of the amygdala in the control of aggression in adolescents with IGD. These findings enhance our understanding of social–emotional perception in adolescents with IGD. PMID:26305475

Existential neuroscience: self-esteem moderates neuronal responses to mortality-related stimuli

PubMed Central

Jonas, Eva; Kronbichler, Martin

2014-01-01

According to terror management theory, self-esteem serves as a buffer against existential anxiety. This proposition is well supported empirically, but its neuronal underpinnings are poorly understood. Therefore, in the present neuroimaging study, our aim was to test how self-esteem affects our neural circuitry activation when death-related material is processed. Consistent with previous findings, the bilateral insula responded less to death-related stimuli relative to similarly unpleasant, but death-unrelated sentences, an effect that might reflect a decrease in the sense of oneself in the face of existential threat. In anterior parts of the insula, this ‘deactivation’ effect was more pronounced for high self-esteem individuals, suggesting that the insula might be of core importance to understanding the anxiety-buffering effect of self-esteem. In addition, low self-esteem participants responded with enhanced activation to death-related over unpleasant stimuli in bilateral ventrolateral prefrontal and medial orbitofrontal cortex, suggesting that regulating death-related thoughts might be more effortful to these individuals. Together, this suggests that the anxiety-buffering effect of self-esteem might be implemented in the brain in the form of both insula-dependent awareness mechanisms and prefrontal cortex-dependent regulation mechanisms. PMID:24222712

Dysfunction of the frontolimbic region during swear word processing in young adolescents with Internet gaming disorder.

PubMed

Chun, J-W; Choi, J; Cho, H; Lee, S-K; Kim, D J

2015-08-25

Although the Internet is an important tool in our daily life, the control of Internet use is necessary to address difficult problems. This study set out with the aim of assessing the cognitive control of affective events in Internet gaming disorder (IGD) and has examined the influence of IGD on neural activities with regard to swear words in young adolescents. We demonstrated the differences between adolescents with IGD and healthy control adolescents (HC) with respect to swear, negative and neutral word conditions. Swear words induced more activation in regions related to social interaction and emotional processing such as the superior temporal sulcus, right temporoparietal junction and orbitofrontal cortex (OFC) when compared with negative words. In this study, adolescents with IGD exhibited reduced activation in the right OFC related to cognitive control and in the dorsal anterior cingulate cortex (dACC) related to social rejection during the swear word condition. In addition, adolescents with IGD were negatively correlated with activity in the right amygdala toward swear words, indicating the important role of the amygdala in the control of aggression in adolescents with IGD. These findings enhance our understanding of social-emotional perception in adolescents with IGD.

Positive mood enhances reward-related neural activity

PubMed Central

Nusslock, Robin

2016-01-01

Although behavioral research has shown that positive mood leads to desired outcomes in nearly every major life domain, no studies have directly examined the effects of positive mood on the neural processes underlying reward-related affect and goal-directed behavior. To address this gap, participants in the present fMRI study experienced either a positive (n = 20) or neutral (n = 20) mood induction and subsequently completed a monetary incentive delay task that assessed reward and loss processing. Consistent with prediction, positive mood elevated activity specifically during reward anticipation in corticostriatal neural regions that have been implicated in reward processing and goal-directed behavior, including the nucleus accumbens, caudate, lateral orbitofrontal cortex and putamen, as well as related paralimbic regions, including the anterior insula and ventromedial prefrontal cortex. These effects were not observed during reward outcome, loss anticipation or loss outcome. Critically, this is the first study to report that positive mood enhances reward-related neural activity. Our findings have implications for uncovering the neural mechanisms by which positive mood enhances goal-directed behavior, understanding the malleability of reward-related neural activity, and developing targeted treatments for psychiatric disorders characterized by deficits in reward processing. PMID:26833919

Brain structure is changed in congenital anosmia.

PubMed

Frasnelli, Johannes; Fark, Therese; Lehmann, Jacqueline; Gerber, Johannes; Hummel, Thomas

2013-12-01

Olfactory function in healthy people correlates with structural features of both the olfactory bulb and higher order olfactory processing areas, but we do not yet know how congenital anosmia affects these latter structures. In order to examine this question closer, we acquired T1 weighted magnetic resonance images from 17 subjects with congenital anosmia and from 17 age- and sex-matched controls. We compared white and gray matter volumes as well as cortical thickness between both groups. We found subjects with congenital anosmia to exhibit larger gray matter volumes in the left entorhinal and piriform cortices. Further, they had thicker orbitofrontal cortices bilaterally. Their left piriform cortex was also thicker than that of controls. These findings are in contrast to those observed in acquired anosmia, where reduced olfactory function is associated with reduced volumes and thickness. However, they fit well with observations from other sensory systems, e.g., vision, where congenital sensory loss is associated with a thicker primary cortex. This finding has been attributed to reduced or absent synaptic pruning as a result of missing peripheral sensory input. Our findings suggest that similar mechanisms take place in the olfactory system. © 2013.

Orbitofrontal Cortex Volume and Effortful Control as Prospective Risk Factors for Substance Use Disorder in Adolescence.

PubMed

Cheetham, Ali; Allen, Nicholas B; Whittle, Sarah; Simmons, Julian; Yücel, Murat; Lubman, Dan I

2017-01-01

Orbitofrontal cortex (OFC) dysfunction has been proposed to increase the risk for developing a substance use disorder (SUD) during adolescence. In this study, we suggest that a reduction in OFC volumes might underlie temperament-based risk factors for SUD, and examined whether smaller OFC volumes during early adolescence could predict later development of SUD. Adolescents (n = 107; 58 male, 49 female) underwent structural MRI and completed a self-report measure of temperamental effortful control at age 12. At 3 subsequent assessments (aged 15, 16, and 18) SUD was assessed via a semi-structured clinical interview. By the third assessment, 24 participants (22.4%) had received a lifetime diagnosis of SUD. Smaller volumes of the left OFC, right OFC, and left medial subregions predicted lifetime history of SUD by age 18. Volumes of the left OFC and left lateral subregions were positively correlated with effortful control, and left OFC volumes mediated the relationship between effortful control and SUD. Smaller volumes of the OFC and low effortful control during adolescence appear to be associated phenotypes that increase the risk of subsequent SUD. Further studies examining the temporal sequence of these risk factors are needed to fully understand this relationship. © 2016 S. Karger AG, Basel.

Reward System Activation in Response to Alcohol Advertisements Predicts College Drinking.

PubMed

Courtney, Andrea L; Rapuano, Kristina M; Sargent, James D; Heatherton, Todd F; Kelley, William M

2018-01-01

In this study, we assess whether activation of the brain's reward system in response to alcohol advertisements is associated with college drinking. Previous research has established a relationship between exposure to alcohol marketing and underage drinking. Within other appetitive domains, the relationship between cue exposure and behavioral enactment is known to rely on activation of the brain's reward system. However, the relationship between neural activation to alcohol advertisements and alcohol consumption has not been studied in a nondisordered population. In this cross-sectional study, 53 college students (32 women) completed a functional magnetic resonance imaging scan while viewing alcohol, food, and control (car and technology) advertisements. Afterward, they completed a survey about their alcohol consumption (including frequency of drinking, typical number of drinks consumed, and frequency of binge drinking) over the previous month. In 43 participants (24 women) meeting inclusion criteria, viewing alcohol advertisements elicited activation in the left orbitofrontal cortex and bilateral ventral striatum-regions of the reward system that typically activate to other appetitive rewards and relate to consumption behaviors. Moreover, the level of self-reported drinking correlated with the magnitude of activation in the left orbitofrontal cortex. Results suggest that alcohol cues are processed within the reward system in a way that may motivate drinking behavior.

On framing effects in decision making: linking lateral versus medial orbitofrontal cortex activation to choice outcome processing.

PubMed

Windmann, Sabine; Kirsch, Peter; Mier, Daniela; Stark, Rudolf; Walter, Bertram; Güntürkün, Onur; Vaitl, Dieter

2006-07-01

Two correlates of outcome processing in the orbitofrontal cortex (OFC) have been proposed in the literature: One hypothesis suggests that the lateral/medial division relates to representation of outcome valence (negative vs. positive), and the other suggests that the medial OFC maintains steady stimulus-outcome associations, whereas the lateral OFC represents changing (unsteady) outcomes to prepare for response shifts. These two hypotheses were contrasted by comparing the original with the inverted version of the Iowa Gambling Task in an event-related functional magnetic resonance imaging experiment. Results showed (1) that (caudo) lateral OFC was indeed sensitive to the steadiness of the outcomes and not merely to outcome valence and (2) that the original and the inverted tasks, although both designed to measure sensitivity for future outcomes, were not equivalent as they enacted different behaviors and brain activation patterns. Results are interpreted in terms of Kahneman and Tversky's prospect theory suggesting that cognitions and decisions are biased differentially when probabilistic future rewards are weighed against consistent punishments relative to the opposite scenario [Kahneman, D., & Tversky, A. Choices, values, and frames. American Psychologist, 39, 341-350, 1984]. Specialized processing of unsteady rewards (involving caudolateral OFC) may have developed during evolution in support of goal-related thinking, prospective planning, and problem solving.

Negative Urgency Mediates the Relationship between Amygdala and Orbitofrontal Cortex Activation to Negative Emotional Stimuli and General Risk-Taking

PubMed Central

Cyders, Melissa A.; Dzemidzic, Mario; Eiler, William J.; Coskunpinar, Ayca; Karyadi, Kenny A.; Kareken, David A.

2015-01-01

The tendency toward impulsive behavior under emotional duress (negative and positive urgency) predicts a wide range of maladaptive risk-taking and behavioral disorders. However, it remains unclear how urgency relates to limbic system activity as induced from emotional provocation. This study used functional magnetic resonance imaging to examine the relationship between brain responses to visual emotional stimuli and urgency traits. Twenty-seven social drinkers (mean age = 25.2, 14 males) viewed negative (Neg), neutral (Neu), and positive (Pos) images during 6 fMRI scans. Brain activation was extracted from a priori limbic regions previously identified in studies of emotional provocation. The right posterior orbitofrontal cortex (OFC) and left amygdala were activated in the [Neg>Neu] contrast, whereas the left posterior OFC was activated in the [Pos>Neu] contrast. Negative urgency was related to the right lateral OFC (r = 0.43, P = 0.03) and the left amygdala (r = 0.39, P = 0.04) [Neg>Neu] activation. Negative urgency also mediated the relationship between [Neg>Neu] activation and general risk-taking (regression weights = 3.42 for right OFC and 2.75 for the left amygdala). Emotional cue-induced activation in right lateral OFC and left amygdala might relate to emotion-based risk-taking through negative urgency. PMID:24904065

Effects of emotion and reward motivation on neural correlates of episodic memory encoding: a PET study.

PubMed

Shigemune, Yayoi; Abe, Nobuhito; Suzuki, Maki; Ueno, Aya; Mori, Etsuro; Tashiro, Manabu; Itoh, Masatoshi; Fujii, Toshikatsu

2010-05-01

It is known that emotion and reward motivation promote long-term memory formation. It remains unclear, however, how and where emotion and reward are integrated during episodic memory encoding. In the present study, subjects were engaged in intentional encoding of photographs under four different conditions that were made by combining two factors (emotional valence, negative or neutral; and monetary reward value, high or low for subsequent successful recognition) during H2 15O positron emission tomography (PET) scanning. As for recognition performance, we found significant main effects of emotional valence (negative>neutral) and reward value (high value>low value), without an interaction between the two factors. Imaging data showed that the left amygdala was activated during the encoding conditions of negative pictures relative to neutral pictures, and the left orbitofrontal cortex was activated during the encoding conditions of high reward pictures relative to low reward pictures. In addition, conjunction analysis of these two main effects detected right hippocampal activation. Although we could not find correlations between recognition performance and activity of these three regions, we speculate that the right hippocampus may integrate the effects of emotion (processed in the amygdala) and monetary reward (processed in the orbitofrontal cortex) on episodic memory encoding. 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Some neuroanatomical insights to impulsive aggression in schizophrenia.

PubMed

Leclerc, Marcel P; Regenbogen, Christina; Hamilton, Roy H; Habel, Ute

2018-06-13

Patients with schizophrenia are at increased risk of engaging in violence towards others, compared to both the general population and most other patient groups. We have here explored the role of cortico-limbic impairments in schizophrenia, and have considered these brain regions specifically within the framework of a popular neuroanatomical model of impulsive aggression. In line with this model, evidence in patients with aggressive schizophrenia implicated structural deficits associated with impaired decision-making, emotional control and evaluation, and social information processing, especially in the orbitofrontal and ventrolateral prefrontal cortex. Given the pivotal role of the orbitofrontal and ventrolateral cortex in emotion control and evaluation, structural deficits may result in inappropriate use of socially relevant information and improper recognition of impulses that are in need for regulation. Furthermore, we have extended the original model and incorporated the striatum, important for the generation of aggressive impulses, as well as the hippocampus, a region critical for decision-making, into the model. Lastly, we discuss the question whether structural impairments are specific to aggressive schizophrenia. Our results suggest, that similar findings can be observed in other aggressive patient populations, making the observed impairments non-specific to aggressive schizophrenia. This points towards a shared condition, across pathologies, a potential common denominator being impulsive aggression. Copyright © 2018. Published by Elsevier B.V.

Lateral orbitofrontal cortex partitions mechanisms for fear regulation and alcohol consumption

PubMed Central

Hanlon, Emma; McDannald, Michael A.

2018-01-01

Anxiety disorders and alcohol use disorder are highly comorbid, yet identifying neural dysfunction driving comorbidity has been challenging. Lateral orbitofrontal cortex (lOFC) dysfunction has been independently observed in each disorder. Here we tested the hypothesis that the lOFC is essential to partition mechanisms for fear regulation and alcohol consumption. Specifically, the capacity to regulate fear and the propensity to consume alcohol are unrelated when lOFC is intact, but become linked through lOFC dysfunction. Male Long Evans rats received bilateral, neurotoxic lOFC lesions or sham surgery. Fear regulation was determined by establishing discrimination to danger, uncertainty, and safety cues then shifting the shock probability of the uncertainty cue. Alcohol consumption was assessed through voluntary, intermittent access to 20% ethanol. The neurotoxic lesion approach ensured lOFC dysfunction spanned testing in fear regulation and alcohol consumption. LOFC-lesioned rats demonstrated maladaptive fear generalization during probability shifts, inverting normal prediction error assignment, and subsequently consumed more alcohol. Most novel, fear regulation and alcohol consumption were inextricably linked only in lOFC-lesioned rats: extreme fear regulation predicted excessive alcohol consumption. The results reveal the lOFC is essential to partition mechanisms for fear regulation and alcohol consumption and uncover a plausible source of neural dysfunction contributing to comorbid anxiety disorders and alcohol use disorder. PMID:29856796

Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition

PubMed Central

Murphy, Jillian M.; Ridley, Nicole J.; Vercammen, Ans

2015-01-01

The orbitofrontal cortex (OFC) has been implicated in the capacity to accurately recognise facial expressions. The aim of the current study was to determine if anodal transcranial direct current stimulation (tDCS) targeting the right OFC in healthy adults would enhance facial expression recognition, compared with a sham condition. Across two counterbalanced sessions of tDCS (i.e. anodal and sham), 20 undergraduate participants (18 female) completed a facial expression labelling task comprising angry, disgusted, fearful, happy, sad and neutral expressions, and a control (social judgement) task comprising the same expressions. Responses on the labelling task were scored for accuracy, median reaction time and overall efficiency (i.e. combined accuracy and reaction time). Anodal tDCS targeting the right OFC enhanced facial expression recognition, reflected in greater efficiency and speed of recognition across emotions, relative to the sham condition. In contrast, there was no effect of tDCS to responses on the control task. This is the first study to demonstrate that anodal tDCS targeting the right OFC boosts facial expression recognition. This finding provides a solid foundation for future research to examine the efficacy of this technique as a means to treat facial expression recognition deficits, particularly in individuals with OFC damage or dysfunction. PMID:25971602

Orbitofrontal Dopamine Depletion Upregulates Caudate Dopamine and Alters Behavior via Changes in Reinforcement Sensitivity

PubMed Central

Cardinal, R. N.; Rygula, R.; Hong, Y. T.; Fryer, T. D.; Sawiak, S. J.; Ferrari, V.; Cockcroft, G.; Aigbirhio, F. I.; Robbins, T. W.; Roberts, A. C.

2014-01-01

Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia. PMID:24872570

Significant grey matter changes in a region of the orbitofrontal cortex in healthy participants predicts emotional dysregulation

PubMed Central

Ekman, Carl Johan; Klahr, Johanna; Tigerström, Lars; Rydén, Göran; Johansson, Anette G. M.; Sellgren, Carl; Golkar, Armita; Olsson, Andreas; Öhman, Arne; Ingvar, Martin; Landén, Mikael

2016-01-01

The traditional concept of ‘categorical’ psychiatric disorders has been challenged as many of the symptoms display a continuous distribution in the general population. We suggest that this is the case for emotional dysregulation, a key component in several categorical psychiatric disorder constructs. We used voxel-based magnetic resonance imaging morphometry in healthy human subjects (n = 87) to study how self-reported subclinical symptoms associated with emotional dysregulation relate to brain regions assumed to be critical for emotion regulation. To measure a pure emotional dysregulation, we also corrected for subclinical symptoms of non-emotional attentional dysregulation. We show that such subclinical emotional symptoms correlate negatively with the grey matter volume of lateral orbitofrontal cortex bilaterally—a region assumed to be critical for emotion regulation and dysfunctional in psychiatric disorders involving emotional dysregulation. Importantly, this effect is mediated both by a decrease in volume associated with emotional dysregulation and an increase in volume due to non-emotional attentional dysregulation. Exploratory analysis suggests that other regions involved in emotional processing such as insula and ventral striatum also show a similar reduction in grey matter volume mirroring clinical disorders associated with emotional dysregulation. Our findings support the concept of continuous properties in psychiatric symptomatology. PMID:26078386

The human orbitofrontal cortex monitors outcomes even when no reward is at stake.

PubMed

Schnider, Armin; Treyer, Valerie; Buck, Alfred

2005-01-01

The orbitofrontal cortex (OFC) processes the occurrence or omission of anticipated rewards, but clinical evidence suggests that it might serve as a generic outcome monitoring system, independent of tangible reward. In this positron emission tomography (PET) study, normal human subjects performed a series of tasks in which they simply had to predict behind which one of two colored rectangles a drawing of an object was hidden. While all tasks involved anticipation in that they had an expectation phase between the subject's prediction and the presentation of the outcome, they varied with regards to the uncertainty of outcome. No comment on the correctness of the prediction, no record of ongoing performance, and no reward, not even a score, was provided. Nonetheless, we found strong activation of the OFC: in comparison with a baseline task, the left anterior medial OFC showed activation in all conditions, indicating a basic role in anticipation; the left posterior OFC was activated in all tasks with some uncertainty of outcome, suggesting a role in the monitoring of outcomes; the right medial OFC showed activation exclusively during guessing. The data indicate a generic role of the human OFC, with some topical specificity, in the generation of hypotheses and processing of outcomes, independent of the presence of explicit reward.

Persistent anosmia in a traumatic brain injury patient: role of orbitofrontal cortex.

PubMed

Caminiti, Fabrizia; Ciurleo, Rosella; Bramanti, Placido; Marino, Silvia

2013-01-01

The olfactory loss due to traumatic brain injury is a common clinical condition. The understanding of the cortical areas involved in ability to detect, discriminate and identify the odours is still limited. However, it has been shown that the orbitofrontal cortex (OFC) is involved in the discrimination and recognition of odours and in particular the right OFC has a dominant role in the central processing of smell. This study used the Sniffin' Sticks Test to evaluate olfactory function of a 40-year-old female with persistent post-traumatic anosmia and to have a objective measure method for the follow-up. A marked decrease in the ability to identify and discriminate odours was found. On the other hand the ability to perceive the odours was little compromised. A cerebral Magnetic Resonance Imaging, performed 10 months after the trauma, showed the presence of a post-traumatic scarring in the right frontal lobe involving the OFC. In this case of post-traumatic anosmia, the ability to perceive and recognize odours does not seem to be compromised in the same measure. It is postulated that the post-traumatic outcomes, involving areas of multisensory integration such as the OFC, have an important pathogenetic role in the loss of ability to recognize and discriminate odours.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis

PubMed Central

Premkumar, Preethi; Fannon, Dominic; Sapara, Adegboyega; Peters, Emmanuelle R.; Anilkumar, Anantha P.; Simmons, Andrew; Kuipers, Elizabeth; Kumari, Veena

2015-01-01

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6–8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness. PMID:25659473

Changes in Low-Frequency Fluctuations in Patients with Antisocial Personality Disorder Revealed by Resting-State Functional MRI

PubMed Central

Jiang, Weixiong; Wang, Wei

2014-01-01

Antisocial Personality Disorder (APD) is a personality disorder that is most commonly associated with the legal and criminal justice systems. The study of the brain in APD has important implications in legal contexts and in helping ensure social stability. However, the neural contribution to the high prevalence of APD is still unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of APD. Thirty-two healthy individuals and thirty-five patients with APD were recruited. The amplitude of low-frequency fluctuations (ALFF) was analyzed for the whole brain of all subjects. Our results showed that APD patients had a significant reduction in the ALFF in the right orbitofrontal cortex, the left temporal pole, the right inferior temporal gyrus, and the left cerebellum posterior lobe compared to normal controls. We observed that the right orbitofrontal cortex had a negative correlation between ALFF values and MMPI psychopathic deviate scores. Alterations in ALFF in these specific brain regions suggest that APD patients may be associated with abnormal activities in the fronto-temporal network. We propose that our results may contribute in a clinical and forensic context to a better understanding of APD. PMID:24598769

Contextual Fear Conditioning in Humans: Cortical-Hippocampal and Amygdala Contributions

PubMed Central

Alvarez, Ruben P.; Biggs, Arter; Chen, Gang; Pine, Daniel S.; Grillon, Christian

2008-01-01

Functional imaging studies of cued fear conditioning in humans have largely confirmed findings in animals, but it is unclear whether the brain mechanisms that underlie contextual fear conditioning in animals are also preserved in humans. We investigated this issue using fMRI and virtual reality contexts. Subjects underwent differential context conditioning in which they were repeatedly exposed to two contexts (CXT+ and CXT-) in semi-random order, with contexts counterbalanced across participants. An un-signaled footshock was consistently paired with the CXT+, and no shock was ever delivered in the CXT-. Evidence for context conditioning was established using skin conductance and anxiety ratings. Consistent with animal models centrally implicating the hippocampus and amygdala in a network supporting context conditioning, CXT+ compared to CXT- significantly activated right anterior hippocampus and bilateral amygdala. In addition, context conditioning was associated with activation in posterior orbitofrontal cortex, medial dorsal thalamus, anterior insula, subgenual anterior cingulate, and parahippocampal, inferior frontal and parietal cortices. Structural equation modeling was used to assess interactions among the core brain regions mediating context conditioning. The derived model indicated that medial amygdala was the source of key efferent and afferent connections including input from orbitofrontal cortex. These results provide evidence that similar brain mechanisms may underlie contextual fear conditioning across species. PMID:18550763

Orbitofrontal cortex inactivation impairs between- but not within-session Pavlovian extinction: an associative analysis.

PubMed

Panayi, Marios C; Killcross, Simon

2014-02-01

The orbitofrontal cortex (OFC) is argued to be the neural locus of Pavlovian outcome expectancies. Reinforcement learning theories argue that extinction learning in Pavlovian procedures is caused by the discrepancy between the expected value of the outcome (US) that is elicited by a predictive stimulus (CS), and the lack of experienced US. If the OFC represents Pavlovian outcome expectancies that are necessary for extinction learning, then disrupting OFC function prior to extinction training should impair extinction learning. This was tested. In experiment 1, Long Evans rats received infusions of saline or muscimol targeting the lateral OFC prior to three appetitive Pavlovian extinction sessions. Muscimol infused into the OFC disrupted between-session but not within-session extinction behaviour. This finding was not due to muscimol infusions disrupting the memory consolidation process per se as there was no effect of muscimol infusion when administered immediately post session (experiment 2). These findings support a role for the OFC in representing outcome expectancies that are necessary for learning. A number of ways in which disrupting outcome expectancy information might block learning will be discussed in the context of traditional associative learning theories and the associative structures they depend on. Copyright © 2013 Elsevier Inc. All rights reserved.

Emotional Processing in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis of 25 Functional Neuroimaging Studies.

PubMed

Thorsen, Anders Lillevik; Hagland, Pernille; Radua, Joaquim; Mataix-Cols, David; Kvale, Gerd; Hansen, Bjarne; van den Heuvel, Odile A

2018-06-01

Patients with obsessive-compulsive disorder (OCD) experience aversive emotions in response to obsessions, motivating avoidance and compulsive behaviors. However, there is considerable ambiguity regarding the brain circuitry involved in emotional processing in OCD, especially whether activation is altered in the amygdala. We conducted a systematic literature review and performed a meta-analysis-seed-based d mapping-of 25 whole-brain neuroimaging studies (including 571 patients and 564 healthy control subjects) using functional magnetic resonance imaging or positron emission tomography, comparing brain activation of patients with OCD and healthy control subjects during presentation of emotionally valenced versus neutral stimuli. Meta-regressions were employed to investigate possible moderators. Patients with OCD, compared with healthy control subjects, showed increased activation in the bilateral amygdala, right putamen, orbitofrontal cortex extending into the anterior cingulate and ventromedial prefrontal cortex, and middle temporal and left inferior occipital cortices during emotional processing. Right amygdala hyperactivation was most pronounced in unmedicated patients. Symptom severity was related to increased activation in the orbitofrontal and anterior cingulate cortices and precuneus. Greater comorbidity with mood and anxiety disorders was associated with higher activation in the right amygdala, putamen, and insula as well as with lower activation in the left amygdala and right ventromedial prefrontal cortex. Patients with OCD show increased emotional processing-related activation in limbic, frontal, and temporal regions. Previous mixed evidence regarding the role of the amygdala in OCD has likely been influenced by patient characteristics (such as medication status) and low statistical power. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Regional Neuroplastic Brain Changes in Patients with Chronic Inflammatory and Non-Inflammatory Visceral Pain

PubMed Central

Hong, Jui-Yang; Labus, Jennifer S.; Jiang, Zhiguo; Ashe-Mcnalley, Cody; Dinov, Ivo; Gupta, Arpana; Shi, Yonggang; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R.; Tillisch, Kirsten; Mayer, Emeran A.

2014-01-01

Regional cortical thickness alterations have been reported in many chronic inflammatory and painful conditions, including inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), even though the mechanisms underlying such neuroplastic changes remain poorly understood. In order to better understand the mechanisms contributing to grey matter changes, the current study sought to identify the differences in regional alterations in cortical thickness between healthy controls and two chronic visceral pain syndromes, with and without chronic gut inflammation. 41 healthy controls, 11 IBS subjects with diarrhea, and 16 subjects with ulcerative colitis (UC) underwent high-resolution T1-weighted magnetization-prepared rapid acquisition gradient echo scans. Structural image preprocessing and cortical thickness analysis within the region of interests were performed by using the Laboratory of Neuroimaging Pipeline. Group differences were determined using the general linear model and linear contrast analysis. The two disease groups differed significantly in several cortical regions. UC subjects showed greater cortical thickness in anterior cingulate cortical subregions, and in primary somatosensory cortex compared with both IBS and healthy subjects. Compared with healthy subjects, UC subjects showed lower cortical thickness in orbitofrontal cortex and in mid and posterior insula, while IBS subjects showed lower cortical thickness in the anterior insula. Large effects of correlations between symptom duration and thickness in the orbitofrontal cortex and postcentral gyrus were only observed in UC subjects. The findings suggest that the mechanisms underlying the observed gray matter changes in UC subjects represent a consequence of peripheral inflammation, while in IBS subjects central mechanisms may play a primary role. PMID:24416245

A critical review of sex differences in decision-making tasks: focus on the Iowa Gambling Task.

PubMed

van den Bos, Ruud; Homberg, Judith; de Visser, Leonie

2013-02-01

It has been observed that men and women show performance differences in the Iowa Gambling Task (IGT), a task of decision-making in which subjects through exploration learn to differentiate long-term advantageous from long-term disadvantageous decks of cards: men choose more cards from the long-term advantageous decks than women within the standard number of 100 trials. Here, we aim at discussing psychological mechanisms and neurobiological substrates underlying sex differences in IGT-like decision-making. Our review suggests that women focus on both win-loss frequencies and long-term pay-off of decks, while men focus on long-term pay-off. Furthermore, women may be more sensitive to occasional losses in the long-term advantageous decks than men. As a consequence hereof, women need 40-60 trials in addition before they reach the same level of performance as men. These performance differences are related to differences in activity in the orbitofrontal cortex and dorsolateral prefrontal cortex as well as in serotonergic activity and left-right hemispheric activity. Sex differences in orbitofrontal cortex activity may be due to organisational effects of gonadal hormones early in life. The behavioural and neurobiological differences in the IGT between men and women are an expression of more general sex differences in the regulation of emotions. We discuss these findings in the context of sex differences in information processing related to evolutionary processes. Furthermore we discuss the relationship between these findings and real world decision-making. Copyright © 2012 Elsevier B.V. All rights reserved.

Disrupted Prefrontal Activity during Emotion Processing in Complicated Grief: an fMRI Investigation

PubMed Central

Arizmendi, Brian; Kaszniak, Alfred W.; O’Connor, Mary-Frances

2015-01-01

Complicated Grief, marked by a persistent and intrusive grief lasting beyond the expected period of adaptation, is associated with a relative inability to disengage from idiographic loss-relevant stimuli (O’Connor & Arizmendi, 2014). In other populations, functional magnetic resonance imaging (fMRI) studies investigating the neural networks associated with this bias consistently implicate the anterior cingulate cortex (ACC) during emotion regulation. In the present study, twenty-eight older adults were categorized into three groups based on grief severity: Complicated Grief (n=8), Non-Complicated Grief (n=9), and Nonbereaved, married controls (n=11). Using a block design, all participants completed 8 blocks (20 stimuli per block) of the ecStroop task during fMRI data acquisition. Differences in neural activity during grief-related (as opposed to neutral) stimuli across groups were examined. Those with Complicated Grief showed an absence of increased rostral ACC (rACC) and fronto-cortical recruitment relative to Nonbereaved controls. Activity in the orbitofrontal cortex (x=6, y=54, z=−10) was significantly elevated in the Non-Complicated Grief group when compared to Nonbereaved controls. Post hoc analysis evidenced activity in the dorsal ACC in the Complicated Grief and Nonbereaved groups late in the task. These findings, supported by behavioral data, suggest a relative inability to recruit the regions necessary for successful completion of this emotional task in those with Complicated Grief. This deficit was not observed in recruitment of the orbitofrontal cortex and the rACC during processing of idiographic semantic stimuli in Non-Complicated Grief. PMID:26434802

Disrupted prefrontal activity during emotion processing in complicated grief: An fMRI investigation.

PubMed

Arizmendi, Brian; Kaszniak, Alfred W; O'Connor, Mary-Frances

2016-01-01

Complicated Grief, marked by a persistent and intrusive grief lasting beyond the expected period of adaptation, is associated with a relative inability to disengage from idiographic loss-relevant stimuli (O'Connor and Arizmendi, 2014). In other populations, functional magnetic resonance imaging (fMRI) studies investigating the neural networks associated with this bias consistently implicate the anterior cingulate cortex (ACC) during emotion regulation. In the present study, twenty-eight older adults were categorized into three groups based on grief severity: Complicated Grief (n=8), Non-Complicated Grief (n=9), and Nonbereaved, married controls (n=11). Using a block design, all participants completed 8 blocks (20 stimuli per block) of the ecStroop task during fMRI data acquisition. Differences in neural activity during grief-related (as opposed to neutral) stimuli across groups were examined. Those with Complicated Grief showed an absence of increased rostral ACC (rACC) and fronto-cortical recruitment relative to Nonbereaved controls. Activity in the orbitofrontal cortex (x=6, y=54, z=-10) was significantly elevated in the Non-Complicated Grief group when compared to Nonbereaved controls. Post hoc analysis evidenced activity in the dorsal ACC in the Complicated Grief and Nonbereaved groups late in the task. These findings, supported by behavioral data, suggest a relative inability to recruit the regions necessary for successful completion of this emotional task in those with Complicated Grief. This deficit was not observed in recruitment of the orbitofrontal cortex and the rACC during processing of idiographic semantic stimuli in Non-Complicated Grief. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

PubMed Central

Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

2016-01-01

Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

Regional cerebral blood flow changes associated with clitorally induced orgasm in healthy women.

PubMed

Georgiadis, Janniko R; Kortekaas, Rudie; Kuipers, Rutger; Nieuwenburg, Arie; Pruim, Jan; Reinders, A A T Simone; Holstege, Gert

2006-12-01

There is a severe lack of knowledge regarding the brain regions involved in human sexual performance in general, and female orgasm in particular. We used [15O]-H2O positron emission tomography to measure regional cerebral blood flow (rCBF) in 12 healthy women during a nonsexual resting state, clitorally induced orgasm, sexual clitoral stimulation (sexual arousal control) and imitation of orgasm (motor output control). Extracerebral markers of sexual performance and orgasm were rectal pressure variability (RPstd) and perceived level of sexual arousal (PSA). Sexual stimulation of the clitoris (compared to rest) significantly increased rCBF in the left secondary and right dorsal primary somatosensory cortex, providing the first account of neocortical processing of sexual clitoral information. In contrast, orgasm was mainly associated with profound rCBF decreases in the neocortex when compared with the control conditions (clitoral stimulation and imitation of orgasm), particularly in the left lateral orbitofrontal cortex, inferior temporal gyrus and anterior temporal pole. Significant positive correlations were found between RPstd and rCBF in the left deep cerebellar nuclei, and between PSA and rCBF in the ventral midbrain and right caudate nucleus. We propose that decreased blood flow in the left lateral orbitofrontal cortex signifies behavioural disinhibition during orgasm in women, and that deactivation of the temporal lobe is directly related to high sexual arousal. In addition, the deep cerebellar nuclei may be involved in orgasm-specific muscle contractions while the involvement of the ventral midbrain and right caudate nucleus suggests a role for dopamine in female sexual arousal and orgasm.

Lateral prefrontal/orbitofrontal cortex has different roles in norm compliance in gain and loss domains: a transcranial direct current stimulation study.

PubMed

Yin, Yunlu; Yu, Hongbo; Su, Zhongbin; Zhang, Yuan; Zhou, Xiaolin

2017-09-01

Sanction is used by almost all known human societies to enforce fairness norm in resource distribution. Previous studies have consistently shown that the lateral prefrontal cortex (lPFC) and the adjacent orbitofrontal cortex (lOFC) play a causal role in mediating the effect of sanction threat on norm compliance. However, most of these studies were conducted in gain domain in which resources are distributed. Little is known about the mechanisms underlying norm compliance in loss domain in which individual sacrifices are needed. Here we employed a modified version of dictator game (DG) and high-definition transcranial direct current stimulation (HD-tDCS) to investigate to what extent lPFC/lOFC is involved in norm compliance (with and without sanction threat) in both gain- and loss-sharing contexts. Participants allocated a fixed total amount of monetary gain or loss between themselves and an anonymous partner in multiple rounds of the game. A computer program randomly decided whether a given round involved sanction threat for the participants. Results showed that disruption of the right lPFC/lOFC by tDCS increased the voluntary norm compliance in the gain domain, but not in the loss domain; tDCS on lPFC/lOFC had no effect on compliance under sanction threat in either the gain or loss domain. Our findings reveal a context-dependent nature of norm compliance and differential roles of lPFC/lOFC in norm compliance in gain and loss domains. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence

PubMed Central

Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Owusu-Duku, Beverly; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.; Miguel-Hidalgo, Jose J.

2014-01-01

Background Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell’s propensity to degenerate or proliferate are changed in the PFC of ALC subjects without major neurological disorders. Methods Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 non-psychiatric comparison subjects. Results ALC subjects had significantly higher levels of the 14kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls. Conclusions Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many alcohol dependent subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics. PMID:25421516

Neurofunctional effects of quetiapine in patients with bipolar mania.

PubMed

Davis, Andrew K; DelBello, Melissa P; Eliassen, James; Welge, Jeffrey; Blom, Thomas J; Fleck, David E; Weber, Wade A; Jarvis, Kelly B; Rummelhoff, Emily; Strakowski, Stephen M; Adler, Caleb M

2015-06-01

Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood. Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans. At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p < 0.001), and increased activation in the right orbitofrontal cortex (OFC) (p = 0.002); there was a significant association between increased right OFC activity and YMRS improvement (p = 0.003). These findings are consistent with suggestions that mania involves a loss of emotional modulatory activity in the prefrontal cortex--restoration of the relatively greater elevation in prefrontal activity widely observed in euthymic patients is associated with clinical improvement. It is not clear, however, whether changes are related to quetiapine treatment or represent a non-specific marker of affective change. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2017-01-05

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

Partially dissociable roles of OFC and ACC in stimulus-guided and action-guided decision making.

PubMed

Khani, Abbas

2014-05-01

Recently, the functional specialization of prefrontal areas of the brain, and, specifically, the functional dissociation of the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), during decision making have become a particular focus of research. A number of neuropsychological and lesion studies have shown that the OFC and ACC have dissociable functions in various dimensions of decision making, which are supported by their different anatomical connections. A recent single-neuron study, however, described a more complex picture of the functional dissociation between these two frontal regions during decision making. Here, I discuss the results of that study and consider alternative interpretations in connection with other findings.

Pivotal response treatment prompts a functional rewiring of the brain among individuals with autism spectrum disorder.

PubMed

Venkataraman, Archana; Yang, Daniel Y-J; Dvornek, Nicha; Staib, Lawrence H; Duncan, James S; Pelphrey, Kevin A; Ventola, Pamela

2016-09-28

Behavioral interventions for autism have gained prominence in recent years; however, the neural-systems-level targets of these interventions remain poorly understood. We use a novel Bayesian framework to extract network-based differences before and after a 16-week pivotal response treatment (PRT) regimen. Our results suggest that the functional changes induced by PRT localize to the posterior cingulate and are marked by a shift in connectivity from the orbitofrontal cortex to the occipital-temporal cortex. Our results illuminate a potential PRT-induced learning mechanism, whereby the neural circuits involved during social perception shift from sensory and attentional systems to higher-level object and face processing areas.

Pivotal Response Treatment Prompts a Functional Rewiring of the Brain amongst Individuals with Autism Spectrum Disorder

PubMed Central

Venkataraman, Archana; Yang, Daniel Y.-J.; Dvornek, Nicha; Staib, Lawrence H.; Duncan, James S.; Pelphrey, Kevin A.; Ventola, Pamela

2016-01-01

Behavioral interventions for autism have gained prominence in recent years; however, the neural-systems-level targets of these interventions remain poorly understood. We use a novel Bayesian framework to extract network-based differences before and after a 16-week Pivotal Response Treatment (PRT) regimen. Our results suggest that functional changes induced by PRT localize to the posterior cingulate and are marked by a shift in connectivity from the orbitofrontal cortex to the occipital temporal cortex. Our results illuminate a potential PRT-induced learning mechanism, whereby the neural circuits involved during social perception shift from sensory and attentional systems to higher-level object and face processing areas. PMID:27532879

Alterations of decision making and underlying neural correlates after resection of a mediofrontal cortical dysplasia: A single case study.

PubMed

Labudda, Kirsten; Brand, Matthias; Mertens, Markus; Ebner, Alois; Markowitsch, Hans J; Woermann, Friedrich G

2010-02-01

We investigated the impact of a congenital prefrontal lesion and its resection on decision making under risk and under ambiguity in a patient with right mediofrontal cortical dysplasia. Both kinds of decision making are normally associated with the medial prefrontal cortex. We additionally studied pre- and postsurgical fMRI activations when processing information relevant for risky decision making. Results indicate selective impairments of ambiguous decision making pre- and postsurgically. Decision making under risk was intact. In contrast to healthy subjects the patient exhibited no activation within the dysplastic anterior cingulate cortex but left-sided orbitofrontal activation on the fMRI task suggesting early reorganization processes.

Body language in the brain: constructing meaning from expressive movement.

PubMed

Tipper, Christine M; Signorini, Giulia; Grafton, Scott T

2015-01-01

This fMRI study investigated neural systems that interpret body language-the meaningful emotive expressions conveyed by body movement. Participants watched videos of performers engaged in modern dance or pantomime that conveyed specific themes such as hope, agony, lust, or exhaustion. We tested whether the meaning of an affectively laden performance was decoded in localized brain substrates as a distinct property of action separable from other superficial features, such as choreography, kinematics, performer, and low-level visual stimuli. A repetition suppression (RS) procedure was used to identify brain regions that decoded the meaningful affective state of a performer, as evidenced by decreased activity when emotive themes were repeated in successive performances. Because the theme was the only feature repeated across video clips that were otherwise entirely different, the occurrence of RS identified brain substrates that differentially coded the specific meaning of expressive performances. RS was observed bilaterally, extending anteriorly along middle and superior temporal gyri into temporal pole, medially into insula, rostrally into inferior orbitofrontal cortex, and caudally into hippocampus and amygdala. Behavioral data on a separate task indicated that interpreting themes from modern dance was more difficult than interpreting pantomime; a result that was also reflected in the fMRI data. There was greater RS in left hemisphere, suggesting that the more abstract metaphors used to express themes in dance compared to pantomime posed a greater challenge to brain substrates directly involved in decoding those themes. We propose that the meaning-sensitive temporal-orbitofrontal regions observed here comprise a superordinate functional module of a known hierarchical action observation network (AON), which is critical to the construction of meaning from expressive movement. The findings are discussed with respect to a predictive coding model of action understanding.

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

PubMed

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

2017-07-01

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

Capturing the temporal evolution of choice across prefrontal cortex

PubMed Central

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

2015-01-01

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

The role of the medial prefrontal cortex in the play fighting of rats.

PubMed

Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

2009-12-01

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

The prefrontal cortex and hybrid learning during iterative competitive games.

PubMed

Abe, Hiroshi; Seo, Hyojung; Lee, Daeyeol

2011-12-01

Behavioral changes driven by reinforcement and punishment are referred to as simple or model-free reinforcement learning. Animals can also change their behaviors by observing events that are neither appetitive nor aversive when these events provide new information about payoffs available from alternative actions. This is an example of model-based reinforcement learning and can be accomplished by incorporating hypothetical reward signals into the value functions for specific actions. Recent neuroimaging and single-neuron recording studies showed that the prefrontal cortex and the striatum are involved not only in reinforcement and punishment, but also in model-based reinforcement learning. We found evidence for both types of learning, and hence hybrid learning, in monkeys during simulated competitive games. In addition, in both the dorsolateral prefrontal cortex and orbitofrontal cortex, individual neurons heterogeneously encoded signals related to actual and hypothetical outcomes from specific actions, suggesting that both areas might contribute to hybrid learning. © 2011 New York Academy of Sciences.

The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks

PubMed Central

Vanneste, Sven; De Ridder, Dirk

2012-01-01

Tinnitus is the perception of a sound in the absence of an external sound source. It is characterized by sensory components such as the perceived loudness, the lateralization, the tinnitus type (pure tone, noise-like) and associated emotional components, such as distress and mood changes. Source localization of quantitative electroencephalography (qEEG) data demonstrate the involvement of auditory brain areas as well as several non-auditory brain areas such as the anterior cingulate cortex (dorsal and subgenual), auditory cortex (primary and secondary), dorsal lateral prefrontal cortex, insula, supplementary motor area, orbitofrontal cortex (including the inferior frontal gyrus), parahippocampus, posterior cingulate cortex and the precuneus, in different aspects of tinnitus. Explaining these non-auditory brain areas as constituents of separable subnetworks, each reflecting a specific aspect of the tinnitus percept increases the explanatory power of the non-auditory brain areas involvement in tinnitus. Thus, the unified percept of tinnitus can be considered an emergent property of multiple parallel dynamically changing and partially overlapping subnetworks, each with a specific spontaneous oscillatory pattern and functional connectivity signature. PMID:22586375

Neurons in the Frontal Lobe Encode the Value of Multiple Decision Variables

PubMed Central

Kennerley, Steven W.; Dahmubed, Aspandiar F.; Lara, Antonio H.; Wallis, Jonathan D.

2009-01-01

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making. PMID:18752411

The orbitofrontal oracle: cortical mechanisms for the prediction and evaluation of specific behavioral outcomes.

PubMed

Rudebeck, Peter H; Murray, Elisabeth A

2014-12-17

The orbitofrontal cortex (OFC) has long been associated with the flexible control of behavior and concepts such as behavioral inhibition, self-control, and emotional regulation. These ideas emphasize the suppression of behaviors and emotions, but OFC's affirmative functions have remained enigmatic. Here we review recent work that has advanced our understanding of this prefrontal area and how its functions are shaped through interaction with subcortical structures such as the amygdala. Recent findings have overturned theories emphasizing behavioral inhibition as OFC's fundamental function. Instead, new findings indicate that OFC provides predictions about specific outcomes associated with stimuli, choices, and actions, especially their moment-to-moment value based on current internal states. OFC function thereby encompasses a broad representation or model of an individual's sensory milieu and potential actions, along with their relationship to likely behavioral outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Human fronto-mesolimbic networks guide decisions about charitable donation.

PubMed

Moll, Jorge; Krueger, Frank; Zahn, Roland; Pardini, Matteo; de Oliveira-Souza, Ricardo; Grafman, Jordan

2006-10-17

Humans often sacrifice material benefits to endorse or to oppose societal causes based on moral beliefs. Charitable donation behavior, which has been the target of recent experimental economics studies, is an outstanding contemporary manifestation of this ability. Yet the neural bases of this unique aspect of human altruism, which extends beyond interpersonal interactions, remain obscure. In this article, we use functional magnetic resonance imaging while participants anonymously donated to or opposed real charitable organizations related to major societal causes. We show that the mesolimbic reward system is engaged by donations in the same way as when monetary rewards are obtained. Furthermore, medial orbitofrontal-subgenual and lateral orbitofrontal areas, which also play key roles in more primitive mechanisms of social attachment and aversion, specifically mediate decisions to donate or to oppose societal causes. Remarkably, more anterior sectors of the prefrontal cortex are distinctively recruited when altruistic choices prevail over selfish material interests.

The unique predisposition to criminal violations in frontotemporal dementia.

PubMed

Mendez, Mario F

2010-01-01

Brain disorders can lead to criminal violations. Patients with frontotemporal dementia (FTD) are particularly prone to sociopathic behavior while retaining knowledge of their acts and of moral and conventional rules. This report describes four FTD patients who committed criminal violations in the presence of clear consciousness and sufficiently intact cognition. They understood the nature of their acts and the potential consequences, but did not feel sufficiently concerned to be deterred. FTD involves a unique pathologic combination affecting the ventromedial prefrontal cortex, with altered moral feelings, right anterior temporal loss of emotional empathy, and orbitofrontal changes with disinhibited, compulsive behavior. These case histories and the literature indicate that those with right temporal FTD retain the capacity to tell right from wrong but have the slow and insidious loss of the capacity for moral rationality. Patients with early FTD present a challenge to the criminal justice system to consider alterations in moral cognition before ascribing criminal responsibility.

Construct validity of the Iowa Gambling Task.

PubMed

Buelow, Melissa T; Suhr, Julie A

2009-03-01

The Iowa Gambling Task (IGT) was created to assess real-world decision making in a laboratory setting and has been applied to various clinical populations (i.e., substance abuse, schizophrenia, pathological gamblers) outside those with orbitofrontal cortex damage, for whom it was originally developed. The current review provides a critical examination of lesion, functional neuroimaging, developmental, and clinical studies in order to examine the construct validity of the IGT. The preponderance of evidence provides support for the use of the IGT to detect decision making deficits in clinical populations, in the context of a more comprehensive evaluation. The review includes a discussion of three critical issues affecting the validity of the IGT, as it has recently become available as a clinical instrument: the lack of a concise definition as to what aspect of decision making the IGT measures, the lack of data regarding reliability of the IGT, and the influence of personality and state mood on IGT performance.

Prefrontal cortex based sex differences in tinnitus perception: same tinnitus intensity, same tinnitus distress, different mood.

PubMed

Vanneste, Sven; Joos, Kathleen; De Ridder, Dirk

2012-01-01

Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males. The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG. Females had a higher mean score than male tinnitus patients on the BDI-II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC) extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC), parahippocampal (PHC) areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC). The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional imaging studies related to tinnitus.

Rapid treatment-induced brain changes in pediatric CRPS.

PubMed

Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

2016-03-01

To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

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.

Effort-Based Reinforcement Processing and Functional Connectivity Underlying Amotivation in Medicated Patients with Depression and Schizophrenia.

PubMed

Park, Il Ho; Lee, Boung Chul; Kim, Jae-Jin; Kim, Joong Il; Koo, Min-Seung

2017-04-19

Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry. SIGNIFICANCE STATEMENT Amotivation is present in both depression and schizophrenia. However, treatment involves the use of drugs that enhance serotonin activity in depression and inhibit serotonin and dopamine activity in schizophrenia. Understanding how motivation processed in the mesocorticolimbic and nigostriatal pathways is affected in depression and schizophrenia is important in discovering treatment targets and strategies for amotivation. To our knowledge, this is the first study to compare patients with depression and schizophrenia in a common functional construct. By using an effort-based reinforcement task and examining resting-state functional connectivity in the dopaminergic network, we propose that difference in striato-orbitofrontal dysfunction in effort-based reinforcement between depression and schizophrenia may be related to differences in the extent of functional dysconnectivity in the dopaminergic pathway. Copyright © 2017 the authors 0270-6474/17/374371-11$15.00/0.

Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

PubMed

Paul, Sandra; Beucke, Jan C; Kaufmann, Christian; Mersov, Anna; Heinzel, Stephan; Kathmann, Norbert; Simon, Daniela

2018-04-06

Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

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.

Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

PubMed

Beck, Anne; Wüstenberg, Torsten; Genauck, Alexander; Wrase, Jana; Schlagenhauf, Florian; Smolka, Michael N; Mann, Karl; Heinz, Andreas

2012-08-01

In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. Subsequent relapsers displayed increased brain atrophy in brain areas associated with error monitoring and behavioral control. Correcting for gray matter reductions, we found that, in these patients, alcohol-related cues elicited increased activation in brain areas associated with attentional bias toward these cues and that, in patients who remained abstinent, increased activation and connectivity were observed in brain areas associated with processing of salient or aversive stimuli.

The social evaluation of faces: a meta-analysis of functional neuroimaging studies

PubMed Central

Mende-Siedlecki, Peter; Said, Christopher P.

2013-01-01

Neuroscience research on the social evaluation of faces has accumulated over the last decade, yielding divergent results. We used a meta-analytic technique, multi-level kernel density analysis (MKDA), to analyze 29 neuroimaging studies on face evaluation. Across negative face evaluations, we observed the most consistent activations in bilateral amygdala. Across positive face evaluations, we observed the most consistent activations in medial prefrontal cortex, pregenual anterior cingulate cortex (pgACC), medial orbitofrontal cortex (mOFC), left caudate and nucleus accumbens (NAcc). Based on additional analyses comparing linear and non-linear responses, we propose a ventral/dorsal dissociation within the amygdala, wherein separate populations of neurons code for face valence and intensity, respectively. Finally, we argue that some of the differences between studies are attributable to differences in the typicality of face stimuli. Specifically, extremely attractive faces are more likely to elicit responses in NAcc/caudate and mOFC. PMID:22287188

Motivating forces of human actions. Neuroimaging reward and social interaction.

PubMed

Walter, Henrik; Abler, Birgit; Ciaramidaro, Angela; Erk, Susanne

2005-11-15

In neuroeconomics, reward and social interaction are central concepts to understand what motivates human behaviour. Both concepts are investigated in humans using neuroimaging methods. In this paper, we provide an overview about these results and discuss their relevance for economic behaviour. For reward it has been shown that a system exists in humans that is involved in predicting rewards and thus guides behaviour, involving a circuit including the striatum, the orbitofrontal cortex and the amygdala. Recent studies on social interaction revealed a mentalizing system representing the mental states of others. A central part of this system is the medial prefrontal cortex, in particular the anterior paracingulate cortex. The reward as well as the mentalizing system is engaged in economic decision-making. We will discuss implications of this study for neuromarketing as well as general implications of these results that may help to provide deeper insights into the motivating forces of human behaviour.

Distinct hippocampal functional networks revealed by tractography-based parcellation.

PubMed

Adnan, Areeba; Barnett, Alexander; Moayedi, Massieh; McCormick, Cornelia; Cohn, Melanie; McAndrews, Mary Pat

2016-07-01

Recent research suggests the anterior and posterior hippocampus form part of two distinct functional neural networks. Here we investigate the structural underpinnings of this functional connectivity difference using diffusion-weighted imaging-based parcellation. Using this technique, we substantiated that the hippocampus can be parcellated into distinct anterior and posterior segments. These structurally defined segments did indeed show different patterns of resting state functional connectivity, in that the anterior segment showed greater connectivity with temporal and orbitofrontal cortex, whereas the posterior segment was more highly connected to medial and lateral parietal cortex. Furthermore, we showed that the posterior hippocampal connectivity to memory processing regions, including the dorsolateral prefrontal cortex, parahippocampal, inferior temporal and fusiform gyri and the precuneus, predicted interindividual relational memory performance. These findings provide important support for the integration of structural and functional connectivity in understanding the brain networks underlying episodic memory.

Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

PubMed

Schultz, Wolfram

2004-04-01

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

Brain abnormalities in antisocial individuals: implications for the law.

PubMed

Yang, Yaling; Glenn, Andrea L; Raine, Adrian

2008-01-01

With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

Control of Intermale Aggression by Medial Prefrontal Cortex Activation in the Mouse

PubMed Central

Takahashi, Aki; Nagayasu, Kazuki; Nishitani, Naoya; Kaneko, Shuji; Koide, Tsuyoshi

2014-01-01

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range. PMID:24740241

[Neuroimaging the various symptom dimensions of obsessive-compulsive disorder].

PubMed

Dold, Markus; Aigner, Martin

2009-01-01

Following consensus on fronto-striato-thalamo-frontal dysfunction as the neuronal basis of obsessive-compulsive disorder, and increasing sub-classification of this clinical picture, neurobiological differentiation of the various obsessive symptoms is also attracting interest in neuroimaging research. Original papers studying the neurobiological correlates of the various dimensions of obsessive-compulsive disorder were listed by a systematic literature search. The "washing" factor seems to involve particular brain structures dealing with emotional control (mainly the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and insula), but the predominant areas in the "forbidden thoughts" factor are cognitive control brain regions (mainly basal ganglia and ACC), and in hoarding obsessions and compulsions they are decision-making areas (mainly ventro-medial parts of the OFC and dorso-lateral prefrontal cortex (DLPFC)). The results underline the neurobiological heterogeneity of the obsessive-compulsive disorder clinical picture, pointing the way for future research approaches.

Neural correlates of the happy life: the amplitude of spontaneous low frequency fluctuations predicts subjective well-being.

PubMed

Kong, Feng; Hu, Siyuan; Wang, Xu; Song, Yiying; Liu, Jia

2015-02-15

Subjective well-being is assumed to be distributed in the hedonic hotspots of subcortical and cortical structures. However, the precise neural correlates underlying this construct, especially how it is maintained during the resting state, are still largely unknown. Here, we explored the neural basis of subjective well-being by correlating the regional fractional amplitude of low frequency fluctuations (fALFF) with the self-reported subjective well-being of healthy individuals. Behaviorally, we demonstrated that subjective well-being contained two related but distinct components: cognitive and affective well-being. Neurally, we showed that the fALFF in the bilateral posterior superior temporal gyrus (pSTG), right posterior mid-cingulate cortex (pMCC), right thalamus, left postcentral gyrus (PCG), right lingual gyrus, and left planum temporale (PT) positively predicted cognitive well-being, whereas the fALFF in the bilateral superior frontal gyrus (SFG), right orbitofrontal cortex (OFC), and left inferior temporal gyrus (ITG) negatively predicted cognitive well-being. In contrast, only the fALFF in the right amygdala reliably predicted affective well-being. Furthermore, emotional intelligence partially mediated the effects of the right pSTG and thalamus on cognitive well-being, as well as the effect of the right amygdala on affective well-being. In summary, we provide the first evidence that spontaneous brain activity in multiple regions associated with sensation, social perception, cognition, and emotion contributes to cognitive well-being, whereas the spontaneous brain activity in only one emotion-related region contributes to affective well-being, suggesting that the spontaneous activity of the human brain reflect the efficiency of subjective well-being. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses.

PubMed

Mareckova, Klara; Holsen, Laura M; Admon, Roee; Makris, Nikos; Seidman, Larry; Buka, Stephen; Whitfield-Gabrieli, Susan; Goldstein, Jill M

2016-11-01

Negative affective stimuli elicit behavioral and neural responses which vary on a continuum from adaptive to maladaptive, yet are typically investigated in a dichotomous manner (healthy controls vs. psychiatric diagnoses). This practice may limit our ability to fully capture variance from acute responses to negative affective stimuli to psychopathology at the extreme end. To address this, we conducted a functional magnetic resonance imaging study to examine the neural responses to negative valence/high arousal and neutral valence/low arousal images as a function of dysphoric mood and sex across individuals (n = 99) who represented traditional categories of healthy controls, major depressive disorder, bipolar psychosis, and schizophrenia. Observation of negative (vs. neutral) stimuli elicited blood oxygen-level dependent responses in the following circuitry: periaqueductal gray, hypothalamus (HYPO), amygdala (AMYG), hippocampus (HIPP), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and greater connectivity between AMYG and mPFC. Across all subjects, severity of dysphoric mood was associated with hyperactivity of HYPO, and, among females, right (R) AMYG. Females also demonstrated inverse relationships between severity of dysphoric mood and connectivity between HYPO - R OFC, R AMYG - R OFC, and R AMYG - R HIPP. Overall, our findings demonstrated sex-dependent deficits in response to negative affective stimuli increasing as a function of dysphoric mood state. Females demonstrated greater inability to regulate arousal as mood became more dysphoric. These findings contribute to elucidating biosignatures associated with response to negative stimuli across disorders and suggest the importance of a sex-dependent lens in determining these biosignatures. Hum Brain Mapp 37:3733-3744, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

On the neural control of social emotional behavior

PubMed Central

Roelofs, Karin; Minelli, Alessandra; Mars, Rogier B.; van Peer, Jacobien; Toni, Ivan

2009-01-01

It is known that the orbitofrontal cortex (OFC) is crucially involved in emotion regulation. However, the specific role of the OFC in controlling the behavior evoked by these emotions, such as approach–avoidance (AA) responses, remains largely unexplored. We measured behavioral and neural responses (using fMRI) during the performance of a social task, a reaction time (RT) task where subjects approached or avoided visually presented emotional faces by pulling or pushing a joystick, respectively. RTs were longer for affect-incongruent responses (approach angry faces and avoid happy faces) as compared to affect-congruent responses (approach–happy; avoid–angry). Moreover, affect-incongruent responses recruited increased activity in the left lateral OFC. These behavioral and neural effects emerged only when the subjects responded explicitly to the emotional value of the faces (AA-task) and largely disappeared when subjects responded to an affectively irrelevant feature of the faces during a control (gender evaluation: GE) task. Most crucially, the size of the OFC-effect correlated positively with the size of the behavioral costs of approaching angry faces. These findings qualify the role of the lateral OFC in the voluntary control of social–motivational behavior, emphasizing the relevance of this region for selecting rule-driven stimulus–response associations, while overriding automatic (affect-congruent) stimulus–response mappings. PMID:19047074

Atrophic Patterns of the Frontal-Subcortical Circuits in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

PubMed Central

Zhao, Hui; Li, Xiaoxi; Wu, Wenbo; Li, Zheng; Qian, Lai; Li, ShanShan; Zhang, Bing; Xu, Yun

2015-01-01

Atrophy of the cortical thickness and gray matter volume are regarded as sensitive markers for the early clinical diagnosis of Alzheimer’s disease (AD). This study aimed to investigate differences in atrophy patterns in the frontal-subcortical circuits between MCI and AD, assess whether these differences were essential for the pathologic basis of cognitive impairment. A total of 131 individuals were recruited, including 45 with cognitively normal controls (CN), 46 with MCI, and 40 with AD. FreeSurfer software was used to perform volumetric measurements of the frontal-subcortical circuits from 3.0T magnetic resonance (MR) scans. Data revealed that both MCI and AD subjects had a thinner cortex in the left caudal middle frontal gyrus and the left lateral orbitofrontal gyrus compared with CN individuals. The left lateral orbitofrontal gyrus was also thinner in AD compared with MCI patients. There were no statistically significant differences in the cortical mean curvature among the three groups. Both MCI and AD subjects exhibited smaller bilateral hippocampus volumes compared with CN individuals. The volumes of the bilateral hippocampus and the right putamen were also smaller in AD compared with MCI patients. Logistic regression analyses revealed that the left lateral orbitofrontal gyrus and bilateral hippocampus were risk factors for cognitive impairment. These current results suggest that atrophy was heterogeneous in subregions of the frontal-subcortical circuits in MCI and AD patients. Among these subregions, the reduced thickness of the left lateral orbitofrontal and the smaller volume of the bilateral hippocampus seemed to be markers for predicting cognitive impairment. PMID:26066658

Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

PubMed

Alsaadi, Hanin M; Van Vugt, Dean A

2015-11-01

This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

Social context and perceived agency affects empathy for pain: an event-related fMRI investigation.

PubMed

Akitsuki, Yuko; Decety, Jean

2009-08-15

Studying of the impact of social context on the perception of pain in others is important for understanding the role of intentionality in interpersonal sensitivity, empathy, and implicit moral reasoning. Here we used an event-related fMRI with pain and social context (i.e., the number of individuals in the stimuli) as the two factors to investigate how different social contexts and resulting perceived agency modulate the neural response to the perception of pain in others. Twenty-six healthy participants were scanned while presented with short dynamic visual stimuli depicting painful situations accidentally caused by or intentionally caused by another individual. The main effect of perception of pain was associated with signal increase in the aMCC, insula, somatosensory cortex, SMA and PAG. Importantly, perceiving the presence of another individual led to specific hemodynamic increase in regions involved in representing social interaction and emotion regulation including the temporoparietal junction, medial prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex. Furthermore, the functional connectivity pattern between the left amygdala and other brain areas was modulated by the perceived agency. Our study demonstrates that the social context in which pain occurs modulate the brain response to other's pain. This modulation may reflect successful adaptation to potential danger present in a social interaction. Our results contribute to a better understanding of the neural mechanisms underpinning implicit moral reasoning that concern actions that can harm other people.

A diffusion tensor imaging study of suicide attempters

PubMed Central

Thapa-Chhetry, Binod; Sublette, M. Elizabeth; Sullivan, Gregory M.; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

2014-01-01

Background Few studies have examined white matter abnormalities in suicide attempters using diffusion tensor imaging (DTI). This study sought to identify white matter regions altered in individuals with a prior suicide attempt. Methods DTI scans were acquired in 13 suicide attempters with major depressive disorder (MDD), 39 non-attempters with MDD, and 46 healthy participants (HP). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) was determined in the brain using two methods: region of interest (ROI) and tract-based spatial statistics (TBSS). ROIs were limited a priori to white matter adjacent to the caudal anterior cingulate cortex, rostral anterior cingulate cortex, dorsomedial prefrontal cortex, and medial orbitofrontal cortex. Results Using the ROI approach, suicide attempters had lower FA than MDD non-attempters and HP in the dorsomedial prefrontal cortex. Uncorrected TBSS results confirmed a significant cluster within the right dorsomedial prefrontal cortex indicating lower FA in suicide attempters compared to non-attempters. There were no differences in ADC when comparing suicide attempters, non-attempters and HP groups using ROI or TBSS methods. Conclusions Low FA in the dorsomedial prefrontal cortex was associated with a suicide attempt history. Converging findings from other imaging modalities support this finding, making this region of potential interest in determining the diathesis for suicidal behavior. PMID:24462041

OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

PubMed

Rajkumar, Ramamoorthy; Dawe, Gavin S

2018-04-07

Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Dysfunctional, but not functional, impulsivity is associated with a history of seriously violent behaviour and reduced orbitofrontal and hippocampal volumes in schizophrenia.

PubMed

Kumari, Veena; Barkataki, Ian; Goswami, Sangeeta; Flora, Satinder; Das, Mrigendra; Taylor, Pamela

2009-07-15

Aggression and violent acts have been linked with impulsive responding. We investigated whether impulsive personality trait, especially suggestive of dysfunctional impulsivity (i.e. fast and inaccurate responding where this is non-optimal), is associated with a history of seriously violent behaviour and specific brain deficits in schizophrenia. Twenty-four male participants with schizophrenia, of whom 10 had a history of serious physical violence, and 14 healthy male participants were assessed on impulsiveness (dysfunctional impulsivity), venturesomeness (functional impulsivity), and empathy. All participants underwent magnetic resonance imaging. The results revealed that participants with schizophrenia and a history of violence showed elevated impulsiveness but had comparable scores on venturesomeness and empathy dimensions. Impulsiveness scores correlated negatively with reduced orbitofrontal grey matter volume in both the patient and healthy control groups, and with hippocampal volume in the patient group. Our findings suggest that dysfunctional, but not functional, impulsivity is elevated in patients with schizophrenia with a propensity for repetitive violence, and this in turn appears to be associated with reduce volumes of both the orbitofrontal cortex grey matter and the hippocampus. Violence risk prediction and management strategies in schizophrenia may benefit from including specific measures of dysfunctional impulsive traits.

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability.

PubMed

Ziminski, Joseph J; Hessler, Sabine; Margetts-Smith, Gabriella; Sieburg, Meike C; Crombag, Hans S; Koya, Eisuke

2017-03-22

Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP- neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell. SIGNIFICANCE STATEMENT Sparsely distributed sets of neurons called "neuronal ensembles" encode learned associations about food and cues predictive of its availability. Widespread changes in neuronal excitability have been observed in limbic brain areas after associative learning, but little is known about the excitability changes that occur specifically on neuronal ensembles that encode appetitive associations. Here, we reveal that sucrose cue exposure recruited a more excitable ensemble in the nucleus accumbens, but not orbitofrontal cortex, compared with their surrounding neurons. This excitability difference was not observed when the cue's salience was diminished after extinction learning. These novel data provide evidence that the intrinsic excitability of appetitive memory-encoding ensembles is regulated differentially across brain areas and adapts dynamically to changes in associative strength. Copyright © 2017 the authors 0270-6474/17/373160-11$15.00/0.

Investigating the separate and interactive associations of trauma and depression on brain structure: implications for cognition and aging.

PubMed

Karstens, Aimee J; Ajilore, Olusola; Rubin, Leah H; Yang, Shaolin; Zhang, Aifeng; Leow, Alex; Kumar, Anand; Lamar, Melissa

2017-11-01

Trauma and depression are associated with brain structural alterations; their combined effects on these outcomes are unclear. We previously reported a negative effect of trauma, independent of depression, on verbal learning and memory; less is known about underlying structural associates. We investigated separate and interactive associations of trauma and depression on brain structure. Adults aged 30-89 (N = 203) evaluated for depression (D+) and trauma history (T+) using structured clinical interviews were divided into 53 D+T+, 42 D+T-, 50 D-T+, and 58 D-T-. Multivariable linear regressions examined the separate and interactive associations of depression and trauma with prefrontal and temporal lobe cortical thickness composites and hippocampal volumes adjusting for age, sex, predicted verbal IQ, comorbid anxiety, and vascular risk. Significant results informed analyses of tract-based structural connectomic measures of efficiency and centrality. Trauma, independent of depression, was associated with greater left prefrontal cortex (PFC) thickness, in particular the medial orbitofrontal cortex and pars orbitalis. A trauma × depression interaction was observed for the right PFC in age-stratified analyses: Older D + T+ had reduced PFC thickness compared with older D - T+ individuals. Regardless of age, trauma was associated with more left medial orbitofrontal cortex efficiency and less pars orbitalis centrality. In the T+ group, left pars orbitalis cortical thickness and centrality negatively correlated with verbal learning. Trauma, independent of depression, associated with altered PFC characteristics, morphologically and in terms of structural network communication and influence. Additionally, findings suggest that there may be a combined effect of trauma and depression in older adults. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Working memory for social cues recruits orbitofrontal cortex and amygdala: a functional magnetic resonance imaging study of delayed matching to sample for emotional expressions.

PubMed

LoPresti, Matthew L; Schon, Karin; Tricarico, Marisa D; Swisher, Jascha D; Celone, Kim A; Stern, Chantal E

2008-04-02

During everyday interactions, we continuously monitor and maintain information about different individuals and their changing emotions in memory. Yet to date, working memory (WM) studies have primarily focused on mechanisms for maintaining face identity, but not emotional expression, and studies investigating the neural basis of emotion have focused on transient activity, not delay related activity. The goal of this functional magnetic resonance imaging study was to investigate WM for two critical social cues: identity and emotion. Subjects performed a delayed match-to-sample task that required them to match either the emotional expression or the identity of a face after a 10 s delay. Neuroanatomically, our predictions focused on the orbitofrontal cortex (OFC) and the amygdala, as these regions have previously been implicated in emotional processing and long-term memory, and studies have demonstrated sustained OFC and medial temporal lobe activity during visual WM. Consistent with previous studies, transient activity during the sample period representing emotion and identity was found in the superior temporal sulcus and inferior occipital cortex, respectively. Sustained delay-period activity was evident in OFC, amygdala, and hippocampus, for both emotion and identity trials. These results suggest that, although initial processing of emotion and identity is accomplished in anatomically segregated temporal and occipital regions, sustained delay related memory for these two critical features is held by the OFC, amygdala and hippocampus. These regions share rich connections, and have been shown previously to be necessary for binding features together in long-term memory. Our results suggest a role for these regions in active maintenance as well.

Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex.

PubMed

Siep, Nicolette; Roefs, Anne; Roebroeck, Alard; Havermans, Remco; Bonte, Milene L; Jansen, Anita

2009-03-02

Research indicates that dysfunctional food reward processing may contribute to pathological eating behaviour. It is widely recognized that both the amygdala and the orbitofrontal cortex (OFC) are essential parts of the brain's reward circuitry. The aims of this fMRI study were (1) to examine the effects of food deprivation and calorie content on reward processing in the amygdala and the OFC, and (2) to examine whether an explicit evaluation of foods is necessary for OFC, but not amygdalar activity. Addressing the first aim, healthy females were presented with high and low calorie food pictures while being either hungry or satiated. For the second aim, attention focus was manipulated by directing participants' attention either to the food or to a neutral aspect. This study shows that hunger interacts with the energy content of foods, modulating activity in the posterior cingulate cortex, medial OFC, insula, caudate putamen and fusiform gyrus. Results show that satiated healthy females show an increased reward processing in response to low calorie foods. Confirming our hypothesis, food deprivation increased activity following the presentation of high calorie foods, which may explain why treatments of obesity energy restricting diets often are unsuccessful. Interestingly, activity in both the amygdala and mOFC was only evident when participants explicitly evaluated foods. However, attention independent activity was found in the mPFC following the high calorie foods cues when participants where hungry. Current findings indicate that research on how attention modulates food reward processing might prove especially insightful in the study of the neural substrates of healthy and pathological eating behaviour.

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

PubMed

Li, Xingbao; Sahlem, Gregory L; Badran, Bashar W; McTeague, Lisa M; Hanlon, Colleen A; Hartwell, Karen J; Henderson, Scott; George, Mark S

2017-12-01

Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794). © 2017 American Academy of Addiction Psychiatry.

Frontostriatal Dysfunction During Decision Making in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder.

PubMed

Norman, Luke J; Carlisi, Christina O; Christakou, Anastasia; Murphy, Clodagh M; Chantiluke, Kaylita; Giampietro, Vincent; Simmons, Andrew; Brammer, Michael; Mataix-Cols, David; Rubia, Katya

2018-03-24

The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity. Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups. Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects. The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cocaine-Induced Structural Plasticity in Input Regions to Distinct Cell Types in Nucleus Accumbens.

PubMed

Barrientos, Cindy; Knowland, Daniel; Wu, Mingche M J; Lilascharoen, Varoth; Huang, Kee Wui; Malenka, Robert C; Lim, Byung Kook

2018-05-09

The nucleus accumbens (NAc) is a brain region implicated in pathological motivated behaviors such as drug addiction and is composed predominantly of two discrete populations of neurons, dopamine receptor-1- and dopamine receptor-2-expressing medium spiny neurons (D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive inputs from different brain areas and whether input regions to these cell types undergo distinct structural adaptations in response to the administration of addictive drugs such as cocaine. Using a modified rabies virus-mediated tracing method, we created a comprehensive brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly 2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus) at four separate time points during cocaine administration and withdrawal to examine changes in spine density in response to repeated intraperitoneal cocaine injection in mice. D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs receive significantly more input from the medial orbitofrontal cortex. We found that neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations in dendritic spine density at different stages of cocaine administration and withdrawal. While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced spine density changes in input regions are quite distinct and dynamic. While previous studies have focused on input-specific postsynaptic changes within NAc MSNs in response to cocaine, these findings emphasize the dramatic changes that occur in the afferent input regions as well. Published by Elsevier Inc.

Neural Mechanisms Underlying Hyperphagia in Prader-Willi Syndrome

PubMed Central

Holsen, Laura M.; Zarcone, Jennifer R.; Brooks, William M.; Butler, Merlin G.; Thompson, Travis I.; Ahluwalia, Jasjit S.; Nollen, Nicole L.; Savage, Cary R.

2006-01-01

Objective Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Research Methods and Procedures Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Results Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Discussion Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and para-limbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC). PMID:16861608

Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol

PubMed Central

Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

2016-01-01

Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer's Disease.

PubMed

Macdonald, Ian R; Maxwell, Selena P; Reid, George A; Cash, Meghan K; DeBay, Drew R; Darvesh, Sultan

2017-01-01

Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aβ, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD (n = 8), NwAβ (n = 6), cognitively normal without plaques (n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aβ and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aβ and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAβ and AD, due to the virtual absence of BChE-associated plaques in NwAβ brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aβ (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management.

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice

PubMed Central

Badanich, Kimberly A.; Becker, Howard C.; Woodward, John J.

2011-01-01

In humans, stroke or trauma-induced damage to the orbitofrontal cortex (OFC) or medial prefrontal cortex (mPFC) results in impaired cognitive flexibility. Alcoholics also exhibit similar deficits in cognitive flexibility suggesting that the OFC and mPFC are susceptible to alcohol-induced dysfunction. The present experiments investigated this issue using an attention set-shifting assay in ethanol dependent adult male C57BL/6J mice. Ethanol dependence was induced by exposing mice to repeated cycles of chronic intermittent ethanol (CIE) vapor inhalation. Behavioral testing was conducted 72 hours or 10 days following CIE exposure to determine whether ethanol-induced changes in OFC-dependent (reversal learning) and mPFC-dependent (set-shifting) behaviors are long-lasting. During early ethanol abstinence (72 hrs), CIE mice showed reduced reversal learning performance as compared to controls. Reversal learning deficits were revealed as greater number of trials to criterion, more errors made and a greater difficulty in performing a reversal learning task relative to baseline performance. Furthermore, the magnitude of the impairment was greater during reversal of a simple discrimination rather than reversal of an intradimensional shift. Reversal learning deficits were no longer present when mice were tested 10 days after CIE exposure suggesting that ethanol-induced changes in OFC function can recover. Unexpectedly, performance on the set-shifting task was not impaired during abstinence from ethanol. These data suggest reversal learning, but not attention set-shifting, is transiently disrupted during short-term abstinence from CIE. Given that reversal learning requires an intact OFC, these findings support the idea that the OFC may be vulnerable to the cognitive impairing actions of ethanol. PMID:22122149

Apoptosis-related proteins and proliferation markers in the orbitofrontal cortex in major depressive disorder

PubMed Central

Miguel-Hidalgo, Jose J.; Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Meshram, Ashish; Pickett, Jason C.; Rajkowska, Grazyna; Stockmeier, Craig A.

2014-01-01

Background: In major depressive disorder (MDD), lowered neural activity and significant reductions of markers of cell resiliency to degeneration occur in the prefrontal cortex (PFC). It is still unclear whether changes in other relevant markers of cell vulnerability to degeneration and markers of cell proliferation are associated with MDD. Methods: Levels of caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA) and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured in postmortem samples of the left orbitofrontal cortex (OFC) of subjects with MDD, and psychiatrically-normal comparison subjects. Results: There was significant increase in C8, a higher ratio of DIABLO to XIAP, lower packing density of Ki-67-IR cells, and an unexpected age-dependent increase in PCNA in subjects with MDD vs. controls. PCNA levels were significantly higher in MDD subjects unresponsive to antidepressants or untreated with antidepressants. The DIABLO/XIAP ratio was higher in MDD subjects without antidepressants than in comparison subjects. Limitations: Qualitative nature of responsiveness assessments; Definition of resistance to antidepressant treatment is still controversial; Unclear role of PCNA. Conclusions: Markers of cell vulnerability to degeneration are increased and density of Ki67-positive cells is low MDD, but accompanied by normal XIAP levels. The results suggest increased vulnerability to cell pathology in depression that is insufficient to cause morphologically conspicuous cell death. Persistent but low-grade vulnerability to cell degeneration coexisting with reduced proliferation readiness may explain age-dependent reductions in neuronal densities in the OFC of depressed subjects. PMID:24655767

Orbitofrontal and limbic signatures of empathic concern and intentional harm in the behavioral variant frontotemporal dementia.

PubMed

Baez, Sandra; Morales, Juan P; Slachevsky, Andrea; Torralva, Teresa; Matus, Cristian; Manes, Facundo; Ibanez, Agustin

2016-02-01

Perceiving and evaluating intentional harms in an interpersonal context engages both cognitive and emotional domains. This process involves inference of intentions, moral judgment, and, crucially, empathy towards others' suffering. This latter skill is notably impaired in behavioral variant frontotemporal dementia (bvFTD). However, the relationship between regional brain atrophy in bvFTD and deficits in the above-mentioned abilities is not well understood. The present study investigated how gray matter (GM) atrophy in bvFTD patients correlates with the perception and evaluation of harmful actions (attribution of intentionality, evaluation of harmful behavior, empathic concern, and moral judgment). First, we compared the behavioral performance of 26 bvFTD patients and 23 healthy controls on an experimental task (ET) indexing intentionality, empathy, and moral cognition during evaluation of harmful actions. Second, we compared GM volume in patients and controls using voxel-based morphometry (VBM). Third, we examined brain regions where atrophy might be associated with specific impairments in the patient group. Finally, we explored whether the patients' deficits in intentionality comprehension and empathic concern could be partially explained by regional GM atrophy or impairments in other relevant factors, such as executive functions (EFs). In bvFTD patients, atrophy of limbic structures (amygdala and anterior paracingulate cortex--APC) was related to impairments in intentionality comprehension, while atrophy of the orbitofrontal cortex (OFC) was associated with empathic concern deficits. Intentionality comprehension impairments were predicted by EFs and orbitofrontal atrophy predicted deficits in empathic concern. Thus, although the perception and evaluation of harmful actions are variously compromised in bvFTD, deficits in empathic concern may be central to this syndrome as they are associated with one of the earliest atrophied region. More generally, our results shed light on social cognition deficits in bvFTD and may have important clinical implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The neurobiological basis of temperament: towards a better understanding of psychopathology.

PubMed

Whittle, Sarah; Allen, Nicholas B; Lubman, Dan I; Yücel, Murat

2006-01-01

The ability to characterise psychopathologies on the basis of their underlying neurobiology is critical in improving our understanding of disorder etiology and making more effective diagnostic and treatment decisions. Given the well-documented relationship between temperament (i.e. core personality traits) and psychopathology, research investigating the neurobiological substrates that underlie temperament is potentially key to our understanding of the biological basis of mental disorder. We present evidence that specific areas of the prefrontal cortex (including the dorsolateral prefrontal, anterior cingulate, and orbitofrontal cortices) and limbic structures (including the amygdala, hippocampus and nucleus accumbens) are key regions associated with three fundamental dimensions of temperament: Negative Affect, Positive Affect, and Constraint. Proposed relationships are based on two types of research: (a) research into the neurobiological correlates of affective and cognitive processes underlying these dimensions; and (b) research into the neurobiology of various psychopathologies, which have been correlated with these dimensions. A model is proposed detailing how these structures might comprise neural networks whose functioning underlies the three temperaments. Recommendations are made for future research into the neurobiology of temperament, including the need to focus on neural networks rather than individual structures, and the importance of prospective, longitudinal, multi-modal imaging studies in at-risk youth.

Is a neutral expression also a neutral stimulus? A study with functional magnetic resonance.

PubMed

Carvajal, Fernando; Rubio, Sandra; Serrano, Juan M; Ríos-Lago, Marcos; Alvarez-Linera, Juan; Pacheco, Lara; Martín, Pilar

2013-08-01

Although neutral faces do not initially convey an explicit emotional message, it has been found that individuals tend to assign them an affective content. Moreover, previous research has shown that affective judgments are mediated by the task they have to perform. Using functional magnetic resonance imaging in 21 healthy participants, we focus this study on the cerebral activity patterns triggered by neutral and emotional faces in two different tasks (social or gender judgments). Results obtained, using conjunction analyses, indicated that viewing both emotional and neutral faces evokes activity in several similar brain areas indicating a common neural substrate. Moreover, neutral faces specifically elicit activation of cerebellum, frontal and temporal areas, while emotional faces involve the cuneus, anterior cingulated gyrus, medial orbitofrontal cortex, posterior superior temporal gyrus, precentral/postcentral gyrus and insula. The task selected was also found to influence brain activity, in that the social task recruited frontal areas while the gender task involved the posterior cingulated, inferior parietal lobule and middle temporal gyrus to a greater extent. Specifically, in the social task viewing neutral faces was associated with longer reaction times and increased activity of left dorsolateral frontal cortex compared with viewing facial expressions of emotions. In contrast, in the same task emotional expressions distinctively activated the left amygdale. The results are discussed taking into consideration the fact that, like other facial expressions, neutral expressions are usually assigned some emotional significance. However, neutral faces evoke a greater activation of circuits probably involved in more elaborate cognitive processing.

Social brain volume is associated with in-degree social network size among older adults

PubMed Central

2018-01-01

The social brain hypothesis proposes that large neocortex size evolved to support cognitively demanding social interactions. Accordingly, previous studies have observed that larger orbitofrontal and amygdala structures predict the size of an individual's social network. However, it remains uncertain how an individual's social connectedness reported by other people is associated with the social brain volume. In this study, we found that a greater in-degree network size, a measure of social ties identified by a subject's social connections rather than by the subject, significantly correlated with a larger regional volume of the orbitofrontal cortex, dorsomedial prefrontal cortex and lingual gyrus. By contrast, out-degree size, which is based on an individual's self-perceived connectedness, showed no associations. Meta-analytic reverse inference further revealed that regional volume pattern of in-degree size was specifically involved in social inference ability. These findings were possible because our dataset contained the social networks of an entire village, i.e. a global network. The results suggest that the in-degree aspect of social network size not only confirms the previously reported brain correlates of the social network but also shows an association in brain regions involved in the ability to infer other people's minds. This study provides insight into understanding how the social brain is uniquely associated with sociocentric measures derived from a global network. PMID:29367402

Determining the neural substrates of goal-directed learning in the human brain.

PubMed

Valentin, Vivian V; Dickinson, Anthony; O'Doherty, John P

2007-04-11

Instrumental conditioning is considered to involve at least two distinct learning systems: a goal-directed system that learns associations between responses and the incentive value of outcomes, and a habit system that learns associations between stimuli and responses without any link to the outcome that that response engendered. Lesion studies in rodents suggest that these two distinct components of instrumental conditioning may be mediated by anatomically distinct neural systems. The aim of the present study was to determine the neural substrates of the goal-directed component of instrumental learning in humans. Nineteen human subjects were scanned with functional magnetic resonance imaging while they learned to choose instrumental actions that were associated with the subsequent delivery of different food rewards (tomato juice, chocolate milk, and orange juice). After training, one of these foods was devalued by feeding the subject to satiety on that food. The subjects were then scanned again, while being re-exposed to the instrumental choice procedure (in extinction). We hypothesized that regions of the brain involved in goal-directed learning would show changes in their activity as a function of outcome devaluation. Our results indicate that neural activity in one brain region in particular, the orbitofrontal cortex, showed a strong modulation in its activity during selection of a devalued compared with a nondevalued action. These results suggest an important contribution of orbitofrontal cortex in guiding goal-directed instrumental choices in humans.

Effect of satiety on brain activation during chocolate tasting in men and women.

PubMed

Smeets, Paul A M; de Graaf, Cees; Stafleu, Annette; van Osch, Matthias J P; Nievelstein, Rutger A J; van der Grond, Jeroen

2006-06-01

The brain plays a crucial role in the decision to eat, integrating multiple hormonal and neural signals. A key factor controlling food intake is selective satiety, ie, the phenomenon that the motivation to eat more of a food decreases more than does the motivation to eat foods not eaten. We investigated the effect of satiation with chocolate on the brain activation associated with chocolate taste in men and women. Twelve men and 12 women participated. Subjects fasted overnight and were scanned by use of functional magnetic resonance imaging while tasting chocolate milk, before and after eating chocolate until they were satiated. In men, chocolate satiation was associated with increased taste activation in the ventral striatum, insula, and orbitofrontal and medial orbitofrontal cortex and with decreased taste activation in somatosensory areas. Women showed increased taste activation in the precentral gyrus, superior temporal gyrus, and putamen and decreased taste activation in the hypothalamus and amygdala. Sex differences in the effect of chocolate satiation were found in the hypothalamus, ventral striatum, and medial prefrontal cortex (all P < 0.005). Our results indicate that men and women differ in their response to satiation and suggest that the regulation of food intake by the brain may vary between the sexes. Therefore, sex differences are a covariate of interest in studies of the brain's responses to food.

Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

PubMed

Pabba, Mohan; Scifo, Enzo; Kapadia, Fenika; Nikolova, Yuliya S; Ma, Tianzhou; Mechawar, Naguib; Tseng, George C; Sibille, Etienne

2017-10-01

The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

PubMed

Drew Sayer, R; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-10-01

The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. © 2016 The Obesity Society.

Reward Sensitivity and Waiting Impulsivity: Shift towards Reward Valuation away from Action Control

PubMed Central

Mechelmans, Daisy J; Strelchuk, Daniela; Doñamayor, Nuria; Banca, Paula; Robbins, Trevor W; Baek, Kwangyeol

2017-01-01

Abstract Background Impulsivity and reward expectancy are commonly interrelated. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here, we assess human waiting impulsivity using a novel translational task, the 4-Choice Serial Reaction Time task, and the relationship with reward cues. Methods Healthy volunteers (n=29) performed the monetary incentive delay task as a functional MRI study where subjects observe a cue predicting reward (cue) and wait to respond for high (£5), low (£1), or no reward. Waiting impulsivity was tested with the 4-Choice Serial Reaction Time task. Results For high reward prospects (£5, no reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial orbitofrontal cortex and lower supplementary motor area activity to cues. In response to high reward cues, greater waiting impulsivity was associated with greater subthalamic nucleus connectivity with orbitofrontal cortex and greater subgenual cingulate connectivity with anterior insula, but decreased connectivity with regions implicated in action selection and preparation. Conclusion These findings highlight a shift towards regions implicated in reward valuation and a shift towards compulsivity away from higher level motor preparation and action selection and response. We highlight the role of reward sensitivity and impulsivity, mechanisms potentially linking human waiting impulsivity with incentive approach and compulsivity, theories highly relevant to disorders of addiction. PMID:29020291

Neural activation in the orbitofrontal cortex in response to male faces increases during the follicular phase

PubMed Central

Rupp, Heather A.; James, Thomas W.; Ketterson, Ellen D.; Sengelaub, Dale R.; Janssen, Erick; Heiman, Julia R.

2009-01-01

Women’s sexual interest changes with hormonal fluctuations across the menstrual cycle. It is unclear how hormones modify women’s sexual behavior and desire, but one possibility is that they alter women’s positive appraisals of stimuli and thus their sexual interest. Using 3 T fMRI, we measured neural activation in women at two time points in their menstrual cycle (late follicular, luteal) while they evaluated photos of men presented as potential sexual partners. Participants were ten heterosexual women aged 23–28 none of who was using hormonal contraceptives or in a committed relationship. In an event-related design, the women were presented with as series of photos of male faces and asked questions to assess their degree of sexual interest in the men depicted. Results demonstrate an overall effect of menstrual cycle phase on neural activation. During their follicular versus luteal phase, women demonstrated increased activation in the right medial orbitofrontal cortex (OFC), suggesting increased positive appraisal. Activation in the OFC was positively correlated with women’s estradiol to progesterone ratios. There were no areas that demonstrated increased activation during the luteal versus follicular phase. The observed increase in activation in the OFC during the follicular phase may reflect a hormonally mediated increase in appetitive motivation and may prime women towards increased sexual interest and behavior around ovulation. PMID:19306881

Model-based learning and the contribution of the orbitofrontal cortex to the model-free world.

PubMed

McDannald, Michael A; Takahashi, Yuji K; Lopatina, Nina; Pietras, Brad W; Jones, Josh L; Schoenbaum, Geoffrey

2012-04-01

Learning is proposed to occur when there is a discrepancy between reward prediction and reward receipt. At least two separate systems are thought to exist: one in which predictions are proposed to be based on model-free or cached values; and another in which predictions are model-based. A basic neural circuit for model-free reinforcement learning has already been described. In the model-free circuit the ventral striatum (VS) is thought to supply a common-currency reward prediction to midbrain dopamine neurons that compute prediction errors and drive learning. In a model-based system, predictions can include more information about an expected reward, such as its sensory attributes or current, unique value. This detailed prediction allows for both behavioral flexibility and learning driven by changes in sensory features of rewards alone. Recent evidence from animal learning and human imaging suggests that, in addition to model-free information, the VS also signals model-based information. Further, there is evidence that the orbitofrontal cortex (OFC) signals model-based information. Here we review these data and suggest that the OFC provides model-based information to this traditional model-free circuitry and offer possibilities as to how this interaction might occur. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Robust Encoding of Spatial Information in Orbitofrontal Cortex and Striatum.

PubMed

Yoo, Seng Bum Michael; Sleezer, Brianna J; Hayden, Benjamin Y

2018-06-01

Knowing whether core reward regions carry information about the positions of relevant objects is crucial for adjudicating between choice models. One limitation of previous studies, including our own, is that spatial positions can be consistently differentially associated with rewards, and thus position can be confounded with attention, motor plans, or target identity. We circumvented these problems by using a task in which value-and thus choices-was determined solely by a frequently changing rule, which was randomized relative to spatial position on each trial. We presented offers asynchronously, which allowed us to control for reward expectation, spatial attention, and motor plans in our analyses. We find robust encoding of the spatial position of both offers and choices in two core reward regions, orbitofrontal Area 13 and ventral striatum, as well as in dorsal striatum of macaques. The trial-by-trial correlation in noise in encoding of position was associated with variation in choice, an effect known as choice probability correlation, suggesting that the spatial encoding is associated with choice and is not incidental to it. Spatial information and reward information are not carried by separate sets of neurons, although the two forms of information are temporally dissociable. These results highlight the ubiquity of multiplexed information in association cortex and argue against the idea that these ostensible reward regions serve as part of a pure value domain.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis.

PubMed

Premkumar, Preethi; Fannon, Dominic; Sapara, Adegboyega; Peters, Emmanuelle R; Anilkumar, Anantha P; Simmons, Andrew; Kuipers, Elizabeth; Kumari, Veena

2015-03-30

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Medial Orbitofrontal Cortex Mediates Effort-related Responding in Rats.

PubMed

Münster, Alexandra; Hauber, Wolfgang

2017-11-17

The medial orbitofrontal cortex (mOFC) is known to support flexible control of goal-directed behavior. However, limited evidence suggests that the mOFC also mediates the ability of organisms to work with vigor towards a selected goal, a hypothesis that received little consideration to date. Here we show that excitotoxic mOFC lesion increased responding under a progressive ratio (PR) schedule of reinforcement, that is, the highest ratio achieved, and increased the preference for the high effort-high reward option in an effort-related decision-making task, but left intact outcome-selective Pavlovian-instrumental transfer and outcome-specific devaluation. Moreover, pharmacological inhibition of the mOFC increased, while pharmacological stimulation reduced PR responding. In addition, pharmacological mOFC stimulation attenuated methylphenidate-induced increase of PR responding. Intact rats tested for PR responding displayed higher numbers of c-Fos positive mOFC neurons than appropriate controls; however, mOFC neurons projecting to the nucleus accumbens did not show a selective increase in neuronal activation implying that they may not play a major role in regulating PR responding. Collectively, these results suggest that the mOFC plays a major role in mediating effort-related motivational functions. Moreover, our data demonstrate for the first time that the mOFC modulates effort-related effects of psychostimulant drugs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effect of bupropion treatment on brain activation induced by cigarette-related cues in smokers.

PubMed

Culbertson, Christopher S; Bramen, Jennifer; Cohen, Mark S; London, Edythe D; Olmstead, Richard E; Gan, Joanna J; Costello, Matthew R; Shulenberger, Stephanie; Mandelkern, Mark A; Brody, Arthur L

2011-05-01

Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Randomized, double-blind, before-after controlled trial. Academic brain imaging center. Thirty nicotine-dependent smokers (paid volunteers). Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans.

PubMed

Elliott, R; Agnew, Z; Deakin, J F W

2008-05-01

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context-dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium-value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision-making network.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity

PubMed Central

Sayer, R Drew; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-01-01

Objective The brain’s reward system influences ingestive behavior and subsequently, obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. We sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. Methods A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n=16) and men (n=12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the 2 testing days. Results Mean fasting-state brain responses on Day 2 were reduced compared to Day 1 in the left insula and right amygdala, but mean Day 1 and Day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. Conclusion fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility, but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. PMID:27542906

Relationships between Cerebral Blood Flow and IQ in Typically Developing Children and Adolescents.

PubMed

Kilroy, Emily; Liu, Collin Y; Yan, Lirong; Kim, Yoon Chun; Dapretto, Mirella; Mendez, Mario F; Wang, Danny J J

2011-01-01

The objective of this study was to explore the relationships between IQ and cerebral blood flow (CBF) measured by arterial spin labeling (ASL) in children and adolescents. ASL was used to collect perfusion MRI data on 39 healthy participants aged 7 to 17. The Wechsler Abbreviated Intelligence Scale was administered to determine IQ scores. Multivariate regression was applied to reveal correlations between CBF and IQ scores, accounting for age, sex and global mean CBF. Voxel Based Morphometry (VBM) analysis, which measures regional cortical volume, was performed as a control. Regression analyses were further performed on CBF data with adjustment of regional gray matter density (GMD). A positive correlation between CBF and IQ scores was primarily seen in the subgenual/anterior cingulate, right orbitofrontal, superior temporal and right inferior parietal regions. An inverse relationship between CBF and IQ was mainly observed in bilateral posterior temporal regions. After adjusting for regional GMD, the correlations between CBF and IQ in the subgenual/anterior cingulate cortex, right orbitofrontal, superior temporal regions and left insula remained significant. These findings support the Parieto-Frontal Integration Theory of intelligence, especially the role of the subgenual/anterior cingulate cortex in the neural networks associated with intelligence. The present study also demonstrates the unique value of CBF in assessing brain-behavior relationships, in addition to structural morphometric measures.

The Neuroanatomy of Genetic Subtype Differences in Prader-Willi Syndrome

PubMed Central

Honea, Robyn A.; Holsen, Laura M.; Lepping, Rebecca J.; Perea, Rodrigo; Butler, Merlin G.; Brooks, William M.; Savage, Cary R.

2012-01-01

Objective Despite behavioral differences between genetic subtypes of Prader-Willi syndrome, no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of Prader-Willi syndrome (PWS) [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Methods Fifteen individuals with PWS due to a typical deletion ((DEL) Type I; n=5, Type II; n=10), 8 with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume between groups, covarying for age, sex, and body mass index (BMI). Results Overall, compared to HWC, PWS individuals had lower gray matter volumes that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower white matter volumes in the brain stem, cerebellum, medial temporal and frontal cortex. Compared to UPD, the DEL subtypes had lower gray matter volume primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and white matter volumes in the orbitofrontal and limbic cortices compared to HWC. Conclusions These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes. PMID:22241551

The neuroanatomy of genetic subtype differences in Prader-Willi syndrome.

PubMed

Honea, Robyn A; Holsen, Laura M; Lepping, Rebecca J; Perea, Rodrigo; Butler, Merlin G; Brooks, William M; Savage, Cary R

2012-03-01

Despite behavioral differences between genetic subtypes of Prader-Willi syndrome (PWS), no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of PWS [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Fifteen individuals with PWS due to a typical deletion [(DEL) type I; n = 5, type II; n = 10], eight with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume (WMV) between groups, covarying for age, sex, and body mass index (BMI). Overall, compared to HWC, PWS individuals had lower gray matter volumes (GMV) that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower WMVs in the brain stem, cerebellum, medial temporal, and frontal cortex. Compared to UPD, the DEL subtypes had lower GMV primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and WMVs in the orbitofrontal and limbic cortices compared to HWC. These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes. Copyright © 2012 Wiley Periodicals, Inc.

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder

PubMed Central

Schulz, Kurt P.; Bédard, Anne-Claude V.; Fan, Jin; Clerkin, Suzanne M.; Dima, Danai; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD. PMID:24918067

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder.

PubMed

Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Clerkin, Suzanne M; Dima, Danai; Newcorn, Jeffrey H; Halperin, Jeffrey M

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD.

Existential neuroscience: self-esteem moderates neuronal responses to mortality-related stimuli.

PubMed

Klackl, Johannes; Jonas, Eva; Kronbichler, Martin

2014-11-01

According to terror management theory, self-esteem serves as a buffer against existential anxiety. This proposition is well supported empirically, but its neuronal underpinnings are poorly understood. Therefore, in the present neuroimaging study, our aim was to test how self-esteem affects our neural circuitry activation when death-related material is processed. Consistent with previous findings, the bilateral insula responded less to death-related stimuli relative to similarly unpleasant, but death-unrelated sentences, an effect that might reflect a decrease in the sense of oneself in the face of existential threat. In anterior parts of the insula, this 'deactivation' effect was more pronounced for high self-esteem individuals, suggesting that the insula might be of core importance to understanding the anxiety-buffering effect of self-esteem. In addition, low self-esteem participants responded with enhanced activation to death-related over unpleasant stimuli in bilateral ventrolateral prefrontal and medial orbitofrontal cortex, suggesting that regulating death-related thoughts might be more effortful to these individuals. Together, this suggests that the anxiety-buffering effect of self-esteem might be implemented in the brain in the form of both insula-dependent awareness mechanisms and prefrontal cortex-dependent regulation mechanisms. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety.

PubMed

Riederer, Franz; Marti, Marvin; Luechinger, Roger; Lanzenberger, Rupert; von Meyenburg, Jan; Gantenbein, Andreas R; Pirrotta, Roberto; Gaul, Charly; Kollias, Spyridon; Sándor, Peter S

2012-10-01

Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems. Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview. Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiety subscale. A GMV increase was found bilaterally in the thalamus, and the ventral striatum. A significant GMV decrease was detected in frontal regions including orbitofrontal cortex, anterior cingulate cortex, the left and right insula, and the precuneus. These findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety. Dysfunction of the reward system may be a neurobiological basis for dependence in a subgroup of MOH patients.

Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting

PubMed Central

Michalska, Kalina J.; Decety, Jean; Liu, Chunyu; Chen, Qi; Martz, Meghan E.; Jacob, Suma; Hipwell, Alison E.; Lee, Steve S.; Chronis-Tuscano, Andrea; Waldman, Irwin D.; Lahey, Benjamin B.

2013-01-01

Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4–6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods. PMID:24550797

Functional specialization of the primate frontal cortex during decision making.

PubMed

Lee, Daeyeol; Rushworth, Matthew F S; Walton, Mark E; Watanabe, Masataka; Sakagami, Masamichi

2007-08-01

Economic theories of decision making are based on the principle of utility maximization, and reinforcement-learning theory provides computational algorithms that can be used to estimate the overall reward expected from alternative choices. These formal models not only account for a large range of behavioral observations in human and animal decision makers, but also provide useful tools for investigating the neural basis of decision making. Nevertheless, in reality, decision makers must combine different types of information about the costs and benefits associated with each available option, such as the quality and quantity of expected reward and required work. In this article, we put forward the hypothesis that different subdivisions of the primate frontal cortex may be specialized to focus on different aspects of dynamic decision-making processes. In this hypothesis, the lateral prefrontal cortex is primarily involved in maintaining the state representation necessary to identify optimal actions in a given environment. In contrast, the orbitofrontal cortex and the anterior cingulate cortex might be primarily involved in encoding and updating the utilities associated with different sensory stimuli and alternative actions, respectively. These cortical areas are also likely to contribute to decision making in a social context.

Regional brain responses associated with drinking water during thirst and after its satiation

PubMed Central

Saker, Pascal; Farrell, Michael J.; Adib, Faiz R. M.; Egan, Gary F.; McKinley, Michael J.; Denton, Derek A.

2014-01-01

The instinct of thirst was a cardinal element in the successful colonization by vertebrates of the dry land of the planet, which began in the Ordovician period about 400 million y ago. It is a commonplace experience in humans that drinking water in response to thirst following fluid loss is a pleasant experience. However, continuing to drink water once thirst has been satiated becomes unpleasant and, eventually, quite aversive. Functional MRI experiments reported here show pleasantness of drinking is associated with activation in the anterior cingulate cortex (Brodmann area 32) and the orbitofrontal cortex. The unpleasantness and aversion of overdrinking is associated with activation in the midcingulate cortex, insula, amygdala, and periaqueductal gray. Drinking activations in the putamen and cerebellum also correlated with the unpleasantness of water, and the motor cortex showed increased activation during overdrinking compared with drinking during thirst. These activations in motor regions may possibly reflect volitional effort to conduct compliant drinking in the face of regulatory mechanisms inhibiting intake. The results suggestive of a specific inhibitory system in the control of drinking are unique. PMID:24706817

Regional brain responses associated with drinking water during thirst and after its satiation.

PubMed

Saker, Pascal; Farrell, Michael J; Adib, Faiz R M; Egan, Gary F; McKinley, Michael J; Denton, Derek A

2014-04-08

The instinct of thirst was a cardinal element in the successful colonization by vertebrates of the dry land of the planet, which began in the Ordovician period about 400 million y ago. It is a commonplace experience in humans that drinking water in response to thirst following fluid loss is a pleasant experience. However, continuing to drink water once thirst has been satiated becomes unpleasant and, eventually, quite aversive. Functional MRI experiments reported here show pleasantness of drinking is associated with activation in the anterior cingulate cortex (Brodmann area 32) and the orbitofrontal cortex. The unpleasantness and aversion of overdrinking is associated with activation in the midcingulate cortex, insula, amygdala, and periaqueductal gray. Drinking activations in the putamen and cerebellum also correlated with the unpleasantness of water, and the motor cortex showed increased activation during overdrinking compared with drinking during thirst. These activations in motor regions may possibly reflect volitional effort to conduct compliant drinking in the face of regulatory mechanisms inhibiting intake. The results suggestive of a specific inhibitory system in the control of drinking are unique.

Neurobiological findings related to Internet use disorders.

PubMed

Park, Byeongsu; Han, Doug Hyun; Roh, Sungwon

2017-07-01

In the last 10 years, numerous neurobiological studies have been conducted on Internet addiction or Internet use disorder. Various neurobiological research methods - such as magnetic resonance imaging; nuclear imaging modalities, including positron emission tomography and single photon emission computed tomography; molecular genetics; and neurophysiologic methods - have made it possible to discover structural or functional impairments in the brains of individuals with Internet use disorder. Specifically, Internet use disorder is associated with structural or functional impairment in the orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. These regions are associated with the processing of reward, motivation, memory, and cognitive control. Early neurobiological research results in this area indicated that Internet use disorder shares many similarities with substance use disorders, including, to a certain extent, a shared pathophysiology. However, recent studies suggest that differences in biological and psychological markers exist between Internet use disorder and substance use disorders. Further research is required for a better understanding of the pathophysiology of Internet use disorder. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Neural correlates of genetically abnormal social cognition in Williams syndrome.

PubMed

Meyer-Lindenberg, Andreas; Hariri, Ahmad R; Munoz, Karen E; Mervis, Carolyn B; Mattay, Venkata S; Morris, Colleen A; Berman, Karen Faith

2005-08-01

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Orbitofrontal gray matter deficits as marker of Internet gaming disorder: converging evidence from a cross-sectional and prospective longitudinal design.

PubMed

Zhou, Feng; Montag, Christian; Sariyska, Rayna; Lachmann, Bernd; Reuter, Martin; Weber, Bernd; Trautner, Peter; Kendrick, Keith M; Markett, Sebastian; Becker, Benjamin

2017-10-23

Internet gaming disorder represents a growing health issue. Core symptoms include unsuccessful attempts to control the addictive patterns of behavior and continued use despite negative consequences indicating a loss of regulatory control. Previous studies revealed brain structural deficits in prefrontal regions subserving regulatory control in individuals with excessive Internet use. However, because of the cross-sectional nature of these studies, it remains unknown whether the observed brain structural deficits preceded the onset of excessive Internet use. Against this background, the present study combined a cross-sectional and longitudinal design to determine the consequences of excessive online video gaming. Forty-one subjects with a history of excessive Internet gaming and 78 gaming-naive subjects were enrolled in the present study. To determine effects of Internet gaming on brain structure, gaming-naive subjects were randomly assigned to 6 weeks of daily Internet gaming (training group) or a non-gaming condition (training control group). At study inclusion, excessive Internet gamers demonstrated lower right orbitofrontal gray matter volume compared with Internet gaming-naive subjects. Within the Internet gamers, a lower gray matter volume in this region was associated with higher online video gaming addiction severity. Longitudinal analysis revealed initial evidence that left orbitofrontal gray matter volume decreased during the training period in the training group as well as in the group of excessive gamers. Together, the present findings suggest an important role of the orbitofrontal cortex in the development of Internet addiction with a direct association between excessive engagement in online gaming and structural deficits in this brain region. © 2017 Society for the Study of Addiction.

Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele.

PubMed

Anders, Silke; Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

2012-04-01

Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia-cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia-cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons ('mirror neurons') in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia-cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease.

Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele

PubMed Central

Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

2012-01-01

Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia–cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia–cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons (‘mirror neurons’) in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia–cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease. PMID:22434215

Effects of acute tryptophan depletion on central processing of CT-targeted and discriminatory touch in humans.

PubMed

Trotter, Paula Diane; McGlone, Francis; McKie, Shane; McFarquhar, Martyn; Elliott, Rebecca; Walker, Susannah Claire; Deakin, John Francis William

2016-08-01

C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT-activating touch engages the pro-social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4 h, participants underwent an fMRI scan, during which time CT-innervated forearm skin and CT non-innervated finger skin was stroked with three brushes of differing texture, at CT-optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to CT-activating forearm touch compared to touch to the finger where CTs are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between CT-activating and purely discriminatory touch responses. Such effects could contribute to some of the social abnormalities seen in psychiatric disorders associated with abnormal serotonin function. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Orbitofrontal and striatal circuits dynamically encode the shift between goal-directed and habitual actions

PubMed Central

Gremel, Christina M.; Costa, Rui M.

2014-01-01

Shifting between goal-directed and habitual actions allows for efficient and flexible decision-making. Here we demonstrate a novel, within-subject instrumental lever-pressing paradigm where mice shift between goal-directed and habitual actions. We identify a role for orbitofrontal cortex (OFC) in actions following outcome-revaluation, and confirm that dorsal medial (DMS) and lateral striatum (DLS) mediate different action strategies. In-vivo simultaneous recordings of OFC, DMS, and DLS neuronal ensembles during shifting reveal that the same neurons display different activity depending on whether presses are goal-directed or habitual, with DMS and OFC becoming more—and DLS less-engaged during goal-directed actions. Importantly, the magnitude of neural activity changes in OFC following changes in outcome value positively correlates with the level of goal-directed behavior. Chemogenetic inhibition of OFC disruptsgoal-directed actions, while optogenetic activation of OFC specifically increases goal-directed pressing. They also reveal a role for OFC in action revaluation, which has implications for understanding compulsive behavior. PMID:23921250

Social cognition and the anterior temporal lobes: a review and theoretical framework

PubMed Central

McCoy, David; Klobusicky, Elizabeth; Ross, Lars A.

2013-01-01

Memory for people and their relationships, along with memory for social language and social behaviors, constitutes a specific type of semantic memory termed social knowledge. This review focuses on how and where social knowledge is represented in the brain. We propose that portions of the anterior temporal lobe (ATL) play a critical role in representing and retrieving social knowledge. This includes memory about people, their names and biographies and more abstract forms of social memory such as memory for traits and social concepts. This hypothesis is based on the convergence of several lines of research including anatomical findings, lesion evidence from both humans and non-human primates and neuroimaging evidence. Moreover, the ATL is closely interconnected with cortical nuclei of the amygdala and orbitofrontal cortex via the uncinate fasciculus. We propose that this pattern of connectivity underlies the function of the ATL in encoding and storing emotionally tagged knowledge that is used to guide orbitofrontal-based decision processes. PMID:23051902

Cortical complexity in bipolar disorder applying a spherical harmonics approach.

PubMed

Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

2017-05-30

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Listening to music in a risk-reward context: The roles of the temporoparietal junction and the orbitofrontal/insular cortices in reward-anticipation, reward-gain, and reward-loss.

PubMed

Li, Chia-Wei; Chen, Jyh-Horng; Tsai, Chen-Gia

2015-12-10

Artificial rewards, such as visual arts and music, produce pleasurable feelings. Popular songs in the verse-chorus form provide a useful model for understanding the neural mechanisms underlying the processing of artificial rewards, because the chorus is usually the most rewarding element of a song. In this functional magnetic resonance imaging (fMRI) study, the stimuli were excerpts of 10 popular songs with a tensioned verse-to-chorus transition. We examined the neural correlates of three phases of reward processing: (1) reward-anticipation during the verse-to-chorus transition, (2) reward-gain during the first phrase of the chorus, and (3) reward-loss during the unexpected noise followed by the verse-to-chorus transition. Participants listened to these excerpts in a risk-reward context because the verse was followed by either the chorus or noise with equal probability. The results showed that reward-gain and reward-loss were associated with left- and right-biased temporoparietal junction activation, respectively. The bilateral temporoparietal junctions were active during reward-anticipation. Moreover, we observed left-biased lateral orbitofrontal activation during reward-anticipation, whereas the medial orbitofrontal cortex was activated during reward-gain. The findings are discussed in relation to the cognitive and emotional aspects of reward processing. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

PubMed Central

Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

2011-01-01

The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

Fighting food temptations: the modulating effects of short-term cognitive reappraisal, suppression and up-regulation on mesocorticolimbic activity related to appetitive motivation.

PubMed

Siep, Nicolette; Roefs, Anne; Roebroeck, Alard; Havermans, Remco; Bonte, Milene; Jansen, Anita

2012-03-01

The premise of cognitive therapy is that one can overcome the irresistible temptation of highly palatable foods by actively restructuring the way one thinks about food. Testing this idea, participants in the present study were instructed to passively view foods, up-regulate food palatability thoughts, apply cognitive reappraisal (e.g., thinking about health consequences), or suppress food palatability thoughts and cravings. We examined whether these strategies affect self-reported food craving and mesocorticolimbic activity as assessed by functional magnetic resonance imaging. It was hypothesized that cognitive reappraisal would most effectively inhibit the mesocorticolimbic activity and associated food craving as compared to suppression. In addition, it was hypothesized that suppression would lead to more prefrontal cortex activity, reflecting the use of more control resources, as compared to cognitive reappraisal. Self-report results indicated that up-regulation increased food craving compared to the other two conditions, but that there was no difference in craving between the suppression and cognitive reappraisal strategy. Corroborating self-report results, the neuroimaging results showed that up-regulation increased activity in important regions of the mesocorticolimbic circuitry, including the ventral tegmental area, ventral striatum, operculum, posterior insular gyrus, medial orbitofrontal cortex and ventromedial prefrontal cortex. Contrary to our hypothesis, suppression more effectively decreased activity in the core of the mesocorticolimbic circuitry (i.e., ventral tegmental area and ventral striatum) compared to cognitive reappraisal. Overall, the results support the contention that appetitive motivation can be modulated by the application of short-term cognitive control strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

The Iowa Gambling Task in fMRI Images

PubMed Central

Li, Xiangrui; Lu, Zhong-Lin; D'Argembeau, Arnaud; Ng, Marie; Bechara, Antoine

2009-01-01

The Iowa Gambling Task (IGT) is a sensitive test for the detection of decision-making impairments in several neurologic and psychiatric populations. Very few studies have employed the IGT in fMRI investigations, in part, because the task is cognitively complex. Here we report a method for exploring brain activity using fMRI during performance of the IGT. Decision-making during the IGT was associated with activity in several brain regions in a group of healthy individuals. The activated regions were consistent with the neural circuitry hypothesized to underlie somatic marker activation and decision-making. Specifically, a neural circuitry involving the dorsolateral prefrontal cortex (for working memory), the insula and posterior cingulate cortex (for representations of emotional states), the mesial orbitofrontal and ventromedial prefrontal cortex (for coupling the two previous processes), the ventral striatum and anterior cingulate/SMA (supplementary motor area) for implementing behavioral decisions was engaged. These results have implications for using the IGT to study abnormal mechanisms of decision making in a variety of clinical populations. PMID:19777556

Effects of adult attachment and emotional distractors on brain mechanisms of cognitive control.

PubMed

Warren, Stacie L; Bost, Kelly K; Roisman, Glenn I; Silton, Rebecca Levin; Spielberg, Jeffrey M; Engels, Anna S; Choi, Eunsil; Sutton, Bradley P; Miller, Gregory A; Heller, Wendy

2010-12-01

Using data from 34 participants who completed an emotion-word Stroop task during functional magnetic resonance imaging, we examined the effects of adult attachment on neural activity associated with top-down cognitive control in the presence of emotional distractors. Individuals with lower levels of secure-base-script knowledge--reflected in an adult's inability to generate narratives in which attachment-related threats are recognized, competent help is provided, and the problem is resolved--demonstrated more activity in prefrontal cortical regions associated with emotion regulation (e.g., right orbitofrontal cortex) and with top-down cognitive control (left dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus). Less efficient performance and related increases in brain activity suggest that insecure attachment involves a vulnerability to distraction by attachment-relevant emotional information and that greater cognitive control is required to attend to task-relevant, nonemotional information. These results contribute to the understanding of mechanisms through which attachment-related experiences may influence developmental adaptation.

Effects of Adult Attachment and Emotional Distractors on Brain Mechanisms of Cognitive Control

PubMed Central

Warren, Stacie L.; Bost, Kelly K.; Roisman, Glenn I.; Silton, Rebecca Levin; Spielberg, Jeffrey M.; Engels, Anna S.; Choi, Eunsil; Sutton, Bradley P.; Miller, Gregory A.; Heller, Wendy

2011-01-01

Using data from 34 participants who completed an emotion-word Stroop task during functional magnetic resonance imaging, we examined the effects of adult attachment on neural activity associated with top-down cognitive control in the presence of emotional distractors. Individuals with lower levels of secure-base-script knowledge—reflected in an adult’s inability to generate narratives in which attachment-related threats are recognized, competent help is provided, and the problem is resolved—demonstrated more activity in prefrontal cortical regions associated with emotion regulation (e.g., right orbitofrontal cortex) and with top-down cognitive control (left dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus). Less efficient performance and related increases in brain activity suggest that insecure attachment involves a vulnerability to distraction by attachment-relevant emotional information and that greater cognitive control is required to attend to task-relevant, nonemotional information. These results contribute to the understanding of mechanisms through which attachment-related experiences may influence developmental adaptation. PMID:21098213

A review of reward processing and motivational impairment in schizophrenia.

PubMed

Strauss, Gregory P; Waltz, James A; Gold, James M

2014-03-01

This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopamine-mediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.

Morphological alterations in the prefrontal cortex and the amygdala in unsuccessful psychopaths.

PubMed

Yang, Yaling; Raine, Adrian; Colletti, Patrick; Toga, Arthur W; Narr, Katherine L

2010-08-01

Although deficits in several cortical and subcortical structures have been found in psychopaths, it remains unclear whether the neuropathology differs between subgroups of psychopaths (i.e., unsuccessful and successful). Using both traditional and novel image analyses methods, this study aims to reveal gross and subtle morphological changes in the prefrontal cortex and the amygdala in unsuccessful and successful psychopaths. Volumetric segmentation, cortical pattern matching, and surface-based mesh modeling methods were used to examine prefrontal and amygdala structures in 16 unsuccessful psychopaths, 10 successful psychopaths, and 27 controls. Significant reduced gray matter volume and cortical thickness/surface shape in the middle frontal, orbitofrontal cortex and the amygdala were found in unsuccessful psychopaths but not successful psychopaths, compared with controls. This study provides the first evidence of greater prefrontal and amygdala structural deficits in unsuccessful psychopaths, which may predispose them to poor behavioral control and impaired decision-making, thus making them more prone to convictions. Copyright 2010 APA, all rights reserved

Neural and behavioral responses to attractiveness in adult and infant faces.

PubMed

Hahn, Amanda C; Perrett, David I

2014-10-01

Facial attractiveness provides a very powerful motivation for sexual and parental behavior. We therefore review the importance of faces to the study of neurobiological control of human reproductive motivations. For heterosexual individuals there is a common brain circuit involving the nucleus accumbens, the medial prefrontal, dorsal anterior cingulate and the orbitofrontal cortices that is activated more by attractive than unattractive faces, particularly for faces of the opposite sex. Behavioral studies indicate parallel effects of attractiveness on incentive salience or willingness to work to see faces. There is some evidence that the reward value of opposite sex attractiveness is more pronounced in men than women, perhaps reflecting the greater importance assigned to physical attractiveness by men when evaluating a potential mate. Sex differences and similarities in response to facial attractiveness are reviewed. Studies comparing heterosexual and homosexual observers indicate the orbitofrontal cortex and mediodorsal thalamus are more activated by faces of the desired sex than faces of the less-preferred sex, independent of observer gender or sexual orientation. Infant faces activate brain regions that partially overlap with those responsive to adult faces. Infant faces provide a powerful stimulus, which also elicits sex differences in behavior and brain responses that appear dependent on sex hormones. There are many facial dimensions affecting perceptions of attractiveness that remain unexplored in neuroimaging, and we conclude by suggesting that future studies combining parametric manipulation of face images, brain imaging, hormone assays and genetic polymorphisms in receptor sensitivity are needed to understand the neural and hormonal mechanisms underlying reproductive drives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective attention to affective value alters how the brain processes olfactory stimuli.

PubMed

Rolls, Edmund T; Grabenhorst, Fabian; Margot, Christian; da Silva, Maria A A P; Velazco, Maria Ines

2008-10-01

How does selective attention to affect influence sensory processing? In a functional magnetic resonance imaging investigation, when subjects were instructed to remember and rate the pleasantness of a jasmine odor, activations were greater in the medial orbito-frontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the odor. When the subjects were instructed to remember and rate the intensity, activations were greater in the inferior frontal gyrus. These top-down effects occurred not only during odor delivery but started in a preparation period after the instruction before odor delivery, and continued after termination of the odor in a short-term memory period. Thus, depending on the context in which odors are presented and whether affect is relevant, the brain prepares itself, responds to, and remembers an odor differently. These findings show that when attention is paid to affective value, the brain systems engaged to prepare for, represent, and remember a sensory stimulus are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus depending on whether the cognitive demand is for affect-related versus more sensory-related processing may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of olfactory but also of other sensory stimuli.

Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers

PubMed Central

Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Olmstead, Richard E.; Gan, Joanna J.; Costello, Matthew R.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.

2011-01-01

Context Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design Randomized, double-blind, before-after controlled trial. Setting Academic brain imaging center. Participants Thirty nicotine-dependent smokers (paid volunteers). Interventions Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. PMID:21199957

Cortical folding in post-traumatic stress disorder after motor vehicle accidents: Regional differences in gyrification.

PubMed

Chu, Chun; Xie, Bing; Qiu, Mingguo; Liu, Kaijun; Tan, Liwen; Wu, Yi; Chen, Wei; Zhang, Shaoxiang

2017-04-01

Structural and functional magnetic resonance imaging (MRI) studies have revealed evidence of brain abnormalities in post-traumatic stress disorder (PTSD) patients. Cortical complexity and local gyrification index (lGI) reflect potential biological processes associated with normal or abnormal cognitive functioning. In the current study, lGI was used to explore cortical folding in PTSD patients involved in motor vehicle accidents (MVA). MRI brain scans were acquired from 18 PTSD patients who had suffered MVA at least 6 months previously and 18 healthy control subjects. All MRI images were obtained on a 3-T Siemens MRI machine and the cortical folding was analyzed using the workflow provided by software FreeSurfer. A general FreeSurfer's general linear model was used in the group analysis. In addition, correlation analysis was performed between the average of lGI extracted from the significantly different areas and the data for the clinical scale. The PTSD patients had significantly greater Clinician-Administered PTSD Scale scores than the control group. The patients showed significantly reduced lGI in the left lateral orbitofrontal cortex, consistent with findings of previous volumetric studies on PTSD. But there were no significant correlations in the left lateral orbitofrontal cortex between Clinician-Administered PTSD Scale scores and lGI. We suggest that abnormal gyrification in PTSD patients can be an important indicator of neurodevelopment deficits and may indeed be a biological marker for PTSD. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Lesions of the Medial Striatum in Monkeys Produce Perseverative Impairments during Reversal Learning Similar to Those Produced by Lesions of the Orbitofrontal Cortex

PubMed Central

Clarke, Hannah F.; Robbins, Trevor W.; Roberts, Angela C.

2014-01-01

The ability to switch responding between two visual stimuli based on their changing relationship with reward is dependent on the orbitofrontal cortex (OFC). OFC lesions in humans, monkeys, and rats disrupt performance on a common test of this ability, the visual serial discrimination reversal task. This finding is of particular significance to our understanding of psychiatric disorders such as obsessive–compulsive disorder (OCD) and schizophrenia, in which behavioral inflexibility is a prominent symptom. Although OFC dysfunction can occur in these disorders, there is considerable evidence for more widespread dysfunction within frontostriatal and frontoamygdalar circuitry. Because the contribution of these subcortical structures to behavioral flexibility is poorly understood, the present study compared the effects of excitotoxic lesions of the medial striatum (MS), amygdala, and OFC in the marmoset monkey on performance of the serial reversal task. All monkeys were able to learn a novel stimulus–reward association but, compared with both control and amygdala-lesioned monkeys, those with MS or OFC lesions showed a perseverative impairment in their ability to reverse this association. However, whereas both MS and OFC groups showed insensitivity to negative feedback, only OFC-lesioned monkeys showed insensitivity to positive feedback. These findings suggest that, for different reasons, both the MS and OFC support behavioral flexibility after changes in reward contingencies, and are consistent with the hypothesis that striatal and OFC dysfunction can contribute to pathological perseveration. PMID:18945905

Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

PubMed Central

Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

2013-01-01

Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

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

Double Dissociation in the Anatomy of Socioemotional Disinhibition and Executive Functioning in Dementia

PubMed Central

Krueger, Casey E.; Laluz, Victor; Rosen, Howard J.; Neuhaus, John M.; Miller, Bruce L.; Kramer, Joel H.

2010-01-01

Objective To determine if socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobe, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. Method Subjects included 157 patients with neurodegenerative disease. A semi-automated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG) and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including three tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single factor score to represent EF. Results Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, MMSE, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition and MFG significantly predicted executive functioning performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. Conclusions These results support a specific association between orbitofrontal areas and behavioral management as compared to dorsolateral areas and EF. PMID:21381829

Orbitofrontal cortex volumes in medication naïve children with major depressive disorder: a magnetic resonance imaging study.

PubMed

Chen, Hua-Hsuan; Rosenberg, David R; MacMaster, Frank P; Easter, Philip C; Caetano, Sheila C; Nicoletti, Mark; Hatch, John P; Nery, Fabiano G; Soares, Jair C

2008-12-01

Adults with major depressive disorder (MDD) are reported to have reduced orbitofrontal cortex (OFC) volumes, which could be related to decreased neuronal density. We conducted a study on medication naïve children with MDD to determine whether abnormalities of OFC are present early in the illness course. Twenty seven medication naïve pediatric Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) MDD patients (mean age +/- SD = 14.4 +/- 2.2 years; 10 males) and 26 healthy controls (mean age +/- SD = 14.4 +/- 2.4 years; 12 males) underwent a 1.5T magnetic resonance imaging (MRI) with 3D spoiled gradient recalled acquisition. The OFC volumes were compared using analysis of covariance with age, gender, and total brain volume as covariates. There was no significant difference in either total OFC volume or total gray matter OFC volume between MDD patients and healthy controls. Exploratory analysis revealed that patients had unexpectedly larger total right lateral (F = 4.2, df = 1, 48, p = 0.05) and right lateral gray matter (F = 4.6, df = 1, 48, p = 0.04) OFC volumes compared to healthy controls, but this finding was not significant following statistical correction for multiple comparisons. No other OFC subregions showed a significant difference. The lack of OFC volume abnormalities in pediatric MDD patients suggests the abnormalities previously reported for adults may develop later in life as a result of neural cell loss.

Effects of testosterone administration on threat and escape anticipation in the orbitofrontal cortex.

PubMed

Heany, Sarah J; Bethlehem, Richard A I; van Honk, Jack; Bos, Peter A; Stein, Dan J; Terburg, David

2018-05-30

Recent evidence suggests that the steroid hormone testosterone can decrease the functional coupling between orbitofrontal cortex (OFC) and amygdala. Theoretically this decoupling has been linked to a testosterone-driven increase of goal-directed behaviour in case of threat, but this has never been studied directly. Therefore, we placed twenty-two women in dynamically changing situations of escapable and inescapable threat after a within-subject placebo controlled testosterone administration. Using functional magnetic resonance imaging (fMRI) we provide evidence that testosterone activates the left lateral OFC (LOFC) in preparation of active goal-directed escape and decouples this OFC area from a subcortical threat system including the central-medial amygdala, hypothalamus and periaqueductal gray. This LOFC decoupling was specific to threatening situations, a point that was further emphasized by an absence of such decoupling in a second experiment focused on resting-state connectivity. These results not only confirm that testosterone administration decouples the LOFC from the subcortical threat system, but also show that this is specifically the case in response to acute threat, and ultimately leads to an increase in LOFC activity when the participant prepares a goal-directed action to escape. Together these results for the first time provide a detailed understanding of functional brain alterations induced by testosterone under threat conditions, and corroborate and extend the view that testosterone prepares the brain for goal-directed action in case of threat. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sex differences in socioemotional functioning, attentional bias, and gray matter volume in maltreated children: A multilevel investigation.

PubMed

Kelly, Philip A; Viding, Essi; Puetz, Vanessa B; Palmer, Amy L; Mechelli, Andrea; Pingault, Jean-Baptiste; Samuel, Sophie; McCrory, Eamon J

2015-11-01

While maltreatment is known to impact social and emotional functioning, threat processing, and neural structure, the potentially dimorphic influence of sex on these outcomes remains relatively understudied. We investigated sex differences across these domains in a large community sample of children aged 10 to 14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 well-matched nonmaltreated peers. The maltreated group relative to the nonmaltreated comparison group exhibited poorer social and emotional functioning (more peer problems and heightened emotional reactivity). Cognitively, they displayed a pattern of attentional avoidance of threat in a visual dot-probe task. Similar patterns were observed in males and females in these domains. Reduced gray matter volume was found to characterize the maltreated group in the medial orbitofrontal cortex, bilateral middle temporal lobes, and bilateral supramarginal gyrus; sex differences were observed only in the supramarginal gyrus. In addition, a disordinal interaction between maltreatment exposure and sex was found in the postcentral gyrus. Finally, attentional avoidance to threat mediated the relationship between maltreatment and emotional reactivity, and medial orbitofrontal cortex gray matter volume mediated the relationship between maltreatment and peer functioning. Similar mediation patterns were observed across sexes. This study highlights the utility of combining multiple levels of analysis when studying the "latent vulnerability" engendered by childhood maltreatment and yields tentative findings regarding a neural basis of sex differences in long-term outcomes for maltreated children.

Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa

PubMed Central

Holsen, Laura M.; Lawson, Elizabeth A.; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M.

2014-01-01

Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. PMID:24862390

Functional inactivation of the orbitofrontal cortex disrupts context-induced reinstatement of alcohol seeking in rats.

PubMed

Bianchi, Paula Cristina; Carneiro de Oliveira, Paulo Eduardo; Palombo, Paola; Leão, Rodrigo Molini; Cogo-Moreira, Hugo; Planeta, Cleopatra da Silva; Cruz, Fábio Cardoso

2018-05-01

The high rate of relapse to drug use remains a central challenge to treating drug addiction. In human and rat models of addiction, environmental stimuli in contexts associated with previous drug use can provoke a relapse of drug seeking. Pre-clinical studies have used the ABA renewal procedure to study context-induced reinstatement of drug seeking. In the current study, we studied the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to alcohol. We trained male and female rats to self-administer alcohol in context A, extinguished drug-reinforced responding in a distinct context B, and assessed context-induced reinstatement in context A or B (control group). Next, we determined the effect of context-induced renewal of alcohol-seeking behavior on the expression of Fos (a neuronal activity marker) in the OFC. Finally, we determined the effect of reversible inactivation by GABAa and GABAb receptor agonists (i.e., muscimol and baclofen, respectively) in the OFC. There were no differences between male and female rats in context-induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but not Context B, reinstated alcohol-seeking behavior and increased expression of the neural activity marker Fos in the OFC. Reversible inactivation of the OFC with muscimol and baclofen attenuated context-induced reinstatement. Our data indicated that the OFC mediates context-induced reinstatement of alcohol-seeking behavior. Copyright © 2018 Elsevier B.V. All rights reserved.