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.

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.

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

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

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.

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.

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.

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.

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

Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion.

PubMed

Xiu, Daiming; Geiger, Maximilian J; Klaver, Peter

2015-01-01

This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

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

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.

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

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.

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

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

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.

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

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

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

Neurobiology of Sensory Overresponsivity in Youth With Autism Spectrum Disorders.

PubMed

Green, Shulamite A; Hernandez, Leanna; Tottenham, Nim; Krasileva, Kate; Bookheimer, Susan Y; Dapretto, Mirella

2015-08-01

More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention. To determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects. Functional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age- and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents' ratings of children's SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014. Relative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex. The mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05). Results demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.

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.

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

(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.

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.

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…

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

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.

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.

Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder.

PubMed

Phan, K Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F; Liberzon, Israel; Arfanakis, Konstantinos

2009-10-01

Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala's response to threat. The goal of this study was to investigate brain frontal WM abnormalities using diffusion tensor imaging (DTI) in patients with social anxiety disorder. A Turboprop DTI sequence was used to acquire diffusion tensor images in 30 patients with GSAD and 30 matched healthy control subjects. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects, and an automated voxel-based, whole-brain method was used to analyze group differences. Compared with healthy control subjects, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD, which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

Of 'disgrace' and 'pain'--corticolimbic interaction patterns for disorder-relevant and emotional words in social phobia.

PubMed

Laeger, Inga; Dobel, Christian; Radenz, Britta; Kugel, Harald; Keuper, Kati; Eden, Annuschka; Arolt, Volker; Zwitserlood, Pienie; Dannlowski, Udo; Zwanzger, Peter

2014-01-01

Limbic hyperactivation and an impaired functional interplay between the amygdala and the prefrontal cortex are discussed to go along with, or even cause, pathological anxiety. Within the multi-faceted group of anxiety disorders, the highly prevalent social phobia (SP) is characterized by excessive fear of being negatively evaluated. Although there is widespread evidence for amygdala hypersensitivity to emotional faces in SP, verbal material has rarely been used in imaging studies, in particular with an eye on disorder-specificity. Using functional magnetic resonance imaging (fMRI) and a block design consisting of (1) overall negative, (2) social-phobia related, (3) positive, and (4) neutral words, we studied 25 female patients with social phobia and 25 healthy female control subjects (HC). Results demonstrated amygdala hyperactivation to disorder-relevant but not to generally negative words in SP patients, with a positive correlation to symptom severity. A functional connectivity analysis revealed a weaker coupling between the amygdala and the left middle frontal gyrus in patients. Symptom severity was negatively related to connectivity strength between the amygdala and the ventromedial prefrontal and orbitofrontal cortex (Brodmann Area 10 and 11). The findings clearly support the view of a hypersensitive threat-detection system, combined with disorder-related alterations in amygdala-prefrontal cortex connectivity in pathological anxiety.

A network of amygdala connections predict individual differences in trait anxiety.

PubMed

Greening, Steven G; Mitchell, Derek G V

2015-12-01

In this study we demonstrate that the pattern of an amygdala-centric network contributes to individual differences in trait anxiety. Individual differences in trait anxiety were predicted using maximum likelihood estimates of amygdala structural connectivity to multiple brain targets derived from diffusion-tensor imaging (DTI) and probabilistic tractography on 72 participants. The prediction was performed using a stratified sixfold cross validation procedure using a regularized least square regression model. The analysis revealed a reliable network of regions predicting individual differences in trait anxiety. Higher trait anxiety was associated with stronger connections between the amygdala and dorsal anterior cingulate cortex, an area implicated in the generation of emotional reactions, and inferior temporal gyrus and paracentral lobule, areas associated with perceptual and sensory processing. In contrast, higher trait anxiety was associated with weaker connections between amygdala and regions implicated in extinction learning such as medial orbitofrontal cortex, and memory encoding and environmental context recognition, including posterior cingulate cortex and parahippocampal gyrus. Thus, trait anxiety is not only associated with reduced amygdala connectivity with prefrontal areas associated with emotion modulation, but also enhanced connectivity with sensory areas. This work provides novel anatomical insight into potential mechanisms behind information processing biases observed in disorders of emotion. © 2015 Wiley Periodicals, Inc.

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.

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.

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.

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.

[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.

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 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

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.

Resting-state functional connectivity in combat veterans suffering from impulsive aggression

PubMed Central

Heesink, Lieke; van Honk, Jack; Geuze, Elbert

2017-01-01

Abstract Impulsive aggression is common among military personnel after deployment and may arise because of impaired top-down regulation of the amygdala by prefrontal regions. This study sought to further explore this hypothesis via resting-state functional connectivity analyses in impulsively aggressive combat veterans. Male combat veterans with (n = 28) and without (n = 30) impulsive aggression problems underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were conducted with the following seed-regions: basolateral amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and anterior insular cortex (AIC). Regions-of-interest analyses focused on the orbitofrontal cortex and periaqueductal gray, and yielded no significant results. In exploratory cluster analyses, we observed reduced functional connectivity between the (bilateral) BLA and left dorsolateral prefrontal cortex in the impulsive aggression group, relative to combat controls. This finding indicates that combat-related impulsive aggression may be marked by weakened functional connectivity between the amygdala and prefrontal regions, already in the absence of explicit emotional stimuli. Group differences in functional connectivity were also observed between the (bilateral) ACC and left cuneus, which may be related to heightened vigilance to potentially threatening visual cues, as well as between the left AIC and right temporal pole, possibly related to negative memory association in impulsive aggression. PMID:29040723

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.

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

PubMed Central

Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

2015-01-01

Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction. PMID:25414039

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

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

Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

PubMed

Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

2017-02-22

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus-reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. Copyright © 2017 the authors 0270-6474/17/372186-17$15.00/0.

Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

PubMed Central

Averbeck, Bruno B.

2017-01-01

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus–reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. PMID:28123082

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.

Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder

PubMed Central

Phan, K. Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F.; Liberzon, Israel; Arfanakis, Konstantinos

2009-01-01

Background Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder. Method A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences. Results Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. Conclusions These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness. PMID:19362707

The neural correlates of sex differences in emotional reactivity and emotion regulation.

PubMed

Domes, Gregor; Schulze, Lars; Böttger, Moritz; Grossmann, Annette; Hauenstein, Karlheinz; Wirtz, Petra H; Heinrichs, Markus; Herpertz, Sabine C

2010-05-01

Sex differences in emotional responding have been repeatedly postulated but less consistently shown in empirical studies. Because emotional reactions are modulated by cognitive appraisal, sex differences in emotional responding might depend on differences in emotion regulation. In this study, we investigated sex differences in emotional reactivity and emotion regulation using a delayed cognitive reappraisal paradigm and measured whole-brain BOLD signal in 17 men and 16 women. During fMRI, participants were instructed to increase, decrease, or maintain their emotional reactions evoked by negative pictures in terms of cognitive reappraisal. We analyzed BOLD responses to aversive compared to neutral pictures in the initial viewing phase and the effect of cognitive reappraisal in the subsequent regulation phase. Women showed enhanced amygdala responding to aversive stimuli in the initial viewing phase, together with increased activity in small clusters within the prefrontal cortex and the temporal cortex. During cognitively decreasing emotional reactions, women recruited parts of the orbitofrontal cortex, the anterior cingulate, and the dorsolateral prefrontal cortex to a lesser extent than men, while there was no sex effect on amygdala activity. In contrast, compared to women, men showed an increased recruitment of regulatory cortical areas during cognitively increasing initial emotional reactions, which was associated with an increase in amygdala activity. Clinical implications of these findings are discussed.

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.

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

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.

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.

Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD

PubMed Central

Huang, Ming-Xiong; Yurgil, Kate A.; Robb, Ashley; Angeles, Annemarie; Diwakar, Mithun; Risbrough, Victoria B.; Nichols, Sharon L.; McLay, Robert; Theilmann, Rebecca J.; Song, Tao; Huang, Charles W.; Lee, Roland R.; Baker, Dewleen G.

2014-01-01

Post-traumatic stress disorder (PTSD) is a leading cause of sustained impairment, distress, and poor quality of life in military personnel, veterans, and civilians. Indirect functional neuroimaging studies using PET or fMRI with fear-related stimuli support a PTSD neurocircuitry model that includes amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC). However, it is not clear if this model can fully account for PTSD abnormalities detected directly by electromagnetic-based source imaging techniques in resting-state. The present study examined resting-state magnetoencephalography (MEG) signals in 25 active-duty service members and veterans with PTSD and 30 healthy volunteers. In contrast to the healthy volunteers, individuals with PTSD showed: 1) hyperactivity from amygdala, hippocampus, posterolateral orbitofrontal cortex (OFC), dorsomedial prefrontal cortex (dmPFC), and insular cortex in high-frequency (i.e., beta, gamma, and high-gamma) bands; 2) hypoactivity from vmPFC, Frontal Pole (FP), and dorsolateral prefrontal cortex (dlPFC) in high-frequency bands; 3) extensive hypoactivity from dlPFC, FP, anterior temporal lobes, precuneous cortex, and sensorimotor cortex in alpha and low-frequency bands; and 4) in individuals with PTSD, MEG activity in the left amygdala and posterolateral OFC correlated positively with PTSD symptom scores, whereas MEG activity in vmPFC and precuneous correlated negatively with symptom score. The present study showed that MEG source imaging technique revealed new abnormalities in the resting-state electromagnetic signals from the PTSD neurocircuitry. Particularly, posterolateral OFC and precuneous may play important roles in the PTSD neurocircuitry model. PMID:25180160

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

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.

Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving.

PubMed

Funk, Douglas; Coen, Kathleen; Tamadon, Sahar; Hope, Bruce T; Shaham, Yavin; Lê, A D

2016-08-17

The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. We trained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos-lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased "incubated" nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation. The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. It is currently unknown whether incubation of craving also occurs after adolescent-onset nicotine self-administration. The brain areas that mediate such incubation are also unknown. Here, we used a rat model of incubation of drug craving, the neuronal activity marker Fos, and the Daun02 chemogenetic inactivation method to demonstrate that incubation of nicotine craving is also observed after adolescent-onset nicotine self-administration and that neuronal ensembles in the central nucleus of the amygdala play a critical role in this incubation in adult rats. Copyright © 2016 the authors 0270-6474/16/368612-12$15.00/0.

Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving

PubMed Central

Coen, Kathleen; Tamadon, Sahar; Hope, Bruce T.; Shaham, Yavin; Lê, A.D.

2016-01-01

The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. We trained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos–lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased “incubated” nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation. SIGNIFICANCE STATEMENT The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. It is currently unknown whether incubation of craving also occurs after adolescent-onset nicotine self-administration. The brain areas that mediate such incubation are also unknown. Here, we used a rat model of incubation of drug craving, the neuronal activity marker Fos, and the Daun02 chemogenetic inactivation method to demonstrate that incubation of nicotine craving is also observed after adolescent-onset nicotine self-administration and that neuronal ensembles in the central nucleus of the amygdala play a critical role in this incubation in adult rats. PMID:27535909

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

Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.

PubMed

Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael D

2016-02-01

Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.

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.

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

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.

Sex differences in structural brain asymmetry predict overt aggression in early adolescents.

PubMed

Visser, Troy A W; Ohan, Jeneva L; Whittle, Sarah; Yücel, Murat; Simmons, Julian G; Allen, Nicholas B

2014-04-01

The devastating social, emotional and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e. left vs right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here, we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.

Opposing Amygdala and Ventral Striatum Connectivity During Emotion Identification

PubMed Central

Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

2011-01-01

Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed a well-characterized emotion identification task. As expected, the amygdala responded to THREAT (angry or fearful) faces more than NON-THREAT (sad or happy) faces. A functional connectivity analysis of the time series from an anatomically defined amygdala seed revealed a strong anti-correlation between the amygdala and the ventral striatum /ventral pallidum, consistent with an opposing role for these regions in during emotion identification. A second functional connectivity analysis (psychophysiological interaction) investigating relative connectivity on THREAT vs. NON-THREAT trials demonstrated that the amygdala had increased connectivity with the orbitofrontal cortex during THREAT trials, whereas the ventral striatum demonstrated increased connectivity with the posterior hippocampus on NON-THREAT trials. These results indicate that activity in the amygdala and ventral striatum may be inversely related, and that both regions may provide opposing affective bias signals during emotion identification. PMID:21600684

The Neural Development of ‘Us and Them’

PubMed Central

Guassi Moreira, João F.; Van Bavel, Jay J.

2017-01-01

Abstract Social groups aid human beings in several ways, ranging from the fulfillment of complex social and personal needs to the promotion of survival. Despite the importance of group affiliation to humans, there remains considerable variation in group preferences across development. In the current study, children and adolescents completed an explicit evaluation task of in-group and out-group members during functional neuroimaging. We found that participants displayed age-related increases in bilateral amygdala, fusiform gyrus and orbitofrontal cortex (OFC) activation when viewing in-group relative to out-group faces. Moreover, we found an indirect effect of age on in-group favoritism via brain activation in the amygdala, fusiform and OFC. Finally, with age, youth showed greater functional coupling between the amygdala and several neural regions when viewing in-group relative to out-group peers, suggesting a role of the amygdala in directing attention to motivationally relevant cues. Our findings suggest that the motivational significance and processing of group membership undergoes important changes across development. PMID:27633395

The orbitofrontal cortex and beyond: from affect to decision-making.

PubMed

Rolls, Edmund T; Grabenhorst, Fabian

2008-11-01

The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. With an origin from beyond the orbitofrontal cortex, top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas of the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of each specific reward in a common currency.

Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques.

PubMed

Wicker, Evan; Turchi, Janita; Malkova, Ludise; Forcelli, Patrick Alexander

2018-05-31

Reward contingencies are dynamic: outcomes that were valued at one point may subsequently lose value. Action selection in the face of dynamic reward associations requires several cognitive processes: registering a change in value of the primary reinforcer, adjusting the value of secondary reinforcers to reflect the new value of the primary reinforcer, and guiding action selection to optimal choices. Flexible responding has been evaluated extensively using reinforcer devaluation tasks. Performance on this task relies upon amygdala, Areas 11 and 13 of orbitofrontal cortex (OFC), and mediodorsal thalamus (MD). Differential contributions of amygdala and Areas 11 and 13 of OFC to specific sub-processes have been established, but the role of MD in these sub-processes is unknown. Pharmacological inactivation of the macaque MD during specific phases of this task revealed that MD is required for reward valuation and action selection. This profile is unique, differing from both amygdala and subregions of the OFC.

Amygdala volume mediates the relationship between externalizing symptoms and daily smoking in adolescence: A prospective study.

PubMed

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

2018-06-30

The current study examined amygdala and orbitofrontal cortex (OFC) volumes as mediators of the relationship between externalizing symptoms and daily smoking in adolescence. Externalizing behaviors are among the most robust predictors of adolescent smoking, and there is emerging evidence that volume reductions in the amygdala and OFC are associated with risk for substance misuse as well as aggressive, impulsive, and disinhibited tendencies. Using a prospective longitudinal design, we recruited 109 adolescents who provided data on brain volume and externalizing behaviors at age 12, and on smoking at age 18. Daily smoking at age 18 (n = 27) was predicted by externalizing behaviors (measured by the self-report Child Behavior Checklist, CBCL) as well as smaller right amygdala volumes. Right amygdala volumes mediated the relationship between externalizing symptoms and later smoking. These findings provide important insight into the neurobiological risk factors associated with adolescent smoking, and, more generally, into factors that may be associated with vulnerability to substance use disorders and related psychopathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control

PubMed Central

Cox, Christine L.; Schmader, Toni; Ryan, Lee

2012-01-01

Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces. PMID:21954239

A neural model of normal and abnormal learning and memory consolidation: adaptively timed conditioning, hippocampus, amnesia, neurotrophins, and consciousness.

PubMed

Franklin, Daniel J; Grossberg, Stephen

2017-02-01

How do the hippocampus and amygdala interact with thalamocortical systems to regulate cognitive and cognitive-emotional learning? Why do lesions of thalamus, amygdala, hippocampus, and cortex have differential effects depending on the phase of learning when they occur? In particular, why is the hippocampus typically needed for trace conditioning, but not delay conditioning, and what do the exceptions reveal? Why do amygdala lesions made before or immediately after training decelerate conditioning while those made later do not? Why do thalamic or sensory cortical lesions degrade trace conditioning more than delay conditioning? Why do hippocampal lesions during trace conditioning experiments degrade recent but not temporally remote learning? Why do orbitofrontal cortical lesions degrade temporally remote but not recent or post-lesion learning? How is temporally graded amnesia caused by ablation of prefrontal cortex after memory consolidation? How are attention and consciousness linked during conditioning? How do neurotrophins, notably brain-derived neurotrophic factor (BDNF), influence memory formation and consolidation? Is there a common output path for learned performance? A neural model proposes a unified answer to these questions that overcome problems of alternative memory models.

Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control.

PubMed

Forbes, Chad E; Cox, Christine L; Schmader, Toni; Ryan, Lee

2012-10-01

Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces.

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

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

Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion

PubMed Central

Rygula, Rafal; Clarke, Hannah F.; Cardinal, Rudolf N.; Cockcroft, Gemma J.; Xia, Jing; Dalley, Jeff W.; Robbins, Trevor W.; Roberts, Angela C.

2015-01-01

Understanding the role of serotonin (or 5-hydroxytryptamine, 5-HT) in aversive processing has been hampered by the contradictory findings, across studies, of increased sensitivity to punishment in terms of subsequent response choice but decreased sensitivity to punishment-induced response suppression following gross depletion of central 5-HT. To address this apparent discrepancy, the present study determined whether both effects could be found in the same animals by performing localized 5-HT depletions in the amygdala or orbitofrontal cortex (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala impaired response choice on a probabilistic visual discrimination task by increasing the effectiveness of misleading, or false, punishment and reward, and decreased response suppression in a variable interval test of punishment sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC also disrupted probabilistic discrimination learning and decreased response suppression. Computational modeling of behavior on the discrimination task showed that the lesions reduced reinforcement sensitivity. A novel, unitary account of the findings in terms of the causal role of 5-HT in the anticipation of both negative and positive motivational outcomes is proposed and discussed in relation to current theories of 5-HT function and our understanding of mood and anxiety disorders. PMID:24879752

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

A multi-pathway hypothesis for human visual fear signaling

PubMed Central

Silverstein, David N.; Ingvar, Martin

2015-01-01

A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the “low road” and “high road,” which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested. PMID:26379513

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

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.

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

Hippocampus and Amygdala Morphology in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Plessen, Kerstin J.; Bansal, Ravi; Zhu, Hongtu; Whiteman, Ronald; Amat, Jose; Quackenbush, Georgette A.; Martin, Laura; Durkin, Kathleen; Blair, Clancy; Royal, Jason; Hugdahl, Kenneth; Peterson, Bradley S.

2008-01-01

Context Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. Objective To study the morphology of the hippocampus and amygdala in children with ADHD. Design A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. Settings University research institute. Patients One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. Main Outcome Measures Volumes and measures of surface morphology for the hippocampus and amygdala. Results The hippocampus was larger bilaterally in the ADHD group than in the control group (t=3.35; P<.002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. Conclusions The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD. PMID:16818869

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.

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

Neuroimaging of psychopathy and antisocial behavior: a targeted review.

PubMed

Blair, R J R

2010-02-01

The goal of this article is to provide a selective and targeted review of the neuroimaging literature on psychopathic tendencies and antisocial behavior and to explore the extent to which this literature supports recent cognitive neuroscientific models of psychopathy and antisocial behavior. The literature reveals that individuals who present with an increased risk for reactive, but not instrumental, aggression show increased amygdala responses to emotionally evocative stimuli. This is consistent with suggestions that such individuals are primed to respond strongly to an inappropriate extent to threatening or frustrating events. In contrast, individuals with psychopathic tendencies show decreased amygdala and orbitofrontal cortex responses to emotionally provocative stimuli or during emotional learning paradigms. This is consistent with suggestions that such individuals face difficulties with basic forms of emotional learning and decision making.

Dendritic Spines in Depression: What We Learned from Animal Models

PubMed Central

Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

2016-01-01

Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms. PMID:26881133

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.

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

PubMed

Ciumas, Carolina; Lindström, Per; Aoun, Bernard; Savic, Ivanka

2008-01-15

Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

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

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

Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits.

PubMed

Kolla, Nathan J; Patel, Raihaan; Meyer, Jeffrey H; Chakravarty, M Mallar

2017-08-29

Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic variants linked to low in vitro transcription (MAOA-L) are associated with structural abnormalities of the amygdala and OFC. However, it is currently unknown whether amygdala and OFC morphology in ASPD relate to MAO-A genetic polymorphisms. We studied 18 ASPD males with a history of violent offending and 20 healthy male controls. Genomic DNA was extracted from peripheral leukocytes to determine MAO-A genetic polymorphisms. Subjects underwent a T1-weighted MRI anatomical brain scan that provided vertex-wise measures of amygdala shape and surface area and OFC cortical thickness. We found that ASPD + PP subjects with MAOA-L exhibited decreased surface area in the right basolateral amygdala nucleus and increased surface area in the right anterior cortical amygdaloid nucleus versus healthy MAOA-L carriers. This study is the first to describe genotype-related morphological differences of the amygdala in a population marked by high aggression. Deficits in emotional regulation that contribute to the violence of ASPD + PP may relate to morphological changes of the amygdala under genetic control.

No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter.

PubMed

Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

2012-04-01

Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.

No Laughing Matter: Intranasal Oxytocin Administration Changes Functional Brain Connectivity during Exposure to Infant Laughter

PubMed Central

Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

2012-01-01

Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent–infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter. PMID:22189289

Posttraumatic Stress Disorder: A Theoretical Model of the Hyperarousal Subtype

PubMed Central

Weston, Charles Stewart E.

2014-01-01

Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework. PMID:24772094

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.

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

Holsen, Laura M; Lawson, Elizabeth A; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M

2014-08-30

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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cortex and amygdala morphology in psychopathy.

PubMed

Boccardi, Marina; Frisoni, Giovanni B; Hare, Robert D; Cavedo, Enrica; Najt, Pablo; Pievani, Michela; Rasser, Paul E; Laakso, Mikko P; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari

2011-08-30

Psychopathy is characterized by abnormal emotional processes, but only recent neuroimaging studies have investigated its cerebral correlates. The study aim was to map local differences of cortical and amygdalar morphology. Cortical pattern matching and radial distance mapping techniques were used to analyze the magnetic resonance images of 26 violent male offenders (age: 32±8) with psychopathy diagnosed using the Psychopathy Checklist-Revised (PCL-R) and no schizophrenia spectrum disorders, and in matched controls (age: 35± sp="0.12"/>11). The cortex displayed up to 20% reduction in the orbitofrontal and midline structures (corrected p<0.001 bilaterally). Up to 30% tissue reduction in the basolateral nucleus, and 10-30% enlargement effects in the central and lateral nuclei indicated abnormal structure of the amygdala (corrected p=0.05 on the right; and symmetrical pattern on the left). Psychopathy features specific morphology of the main cerebral structures involved in cognitive and emotional processing, consistent with clinical and functional data, and with a hypothesis of an alternative evolutionary brain development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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

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.

[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.

The Functions of the Orbitofrontal Cortex

ERIC Educational Resources Information Center

Rolls, Edmund T.

2004-01-01

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight…

Cellular activation in limbic brain systems during social play behaviour in rats.

PubMed

van Kerkhof, Linda W M; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J M J

2014-07-01

Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-Fos as a marker. After a session of social play behaviour, pronounced increases in c-Fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organized in this network, as indicated by play-specific correlations in c-Fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organized neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats.

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

PubMed

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

2015-09-01

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

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.

The psychopath magnetized: insights from brain imaging

PubMed Central

Anderson, Nathaniel E.; Kiehl, Kent A.

2014-01-01

Psychopaths commit a disproportionate amount of violent crime, and this places a substantial economic and emotional burden on society. Elucidation of the neural correlates of psychopathy may lead to improved management and treatment of the condition. Although some methodological issues remain, the neuroimaging literature is generally converging on a set of brain regions and circuits that are consistently implicated in the condition: the orbitofrontal cortex, amygdala, and the anterior and posterior cingulate and adjacent (para)limbic structures. We discuss these findings in the context of extant theories of psychopathy and highlight the potential legal and policy implications of this body of work. PMID:22177031

Social deficits and perseverative behaviors, but not overt aggression, in MAO-A hypomorphic mice.

PubMed

Bortolato, Marco; Chen, Kevin; Godar, Sean C; Chen, Gao; Wu, Weihua; Rebrin, Igor; Farrell, Mollee R; Scott, Anna L; Wellman, Cara L; Shih, Jean C

2011-12-01

Monoamine oxidase (MAO)-A is a key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE). In humans and mice, total MAO-A deficiency results in high 5-HT and NE levels, as well as elevated reactive aggression. Here we report the generation of MAO-A(Neo) mice, a novel line of hypomorphic MAO-A mutants featuring the insertion of a floxed neomycin-resistance cassette in intron-12 of the Maoa gene. This construct resulted in a chimeric, non-functional variant of the Maoa-Neo transcript, with a truncated C-terminus, likely due to aberrant splicing; these deficits notwithstanding, small amounts of functional Maoa transcript were found in the brain of MAO-A(Neo) mice. In the prefrontal cortex and amygdala, MAO-A(Neo) mice showed low, yet detectable, MAO-A catalytic activity, as well as 5-HT levels equivalent to WT littermates; conversely, the hippocampus and midbrain of MAO-A(Neo) mice featured a neurochemical profile akin to MAO-A-knockout (KO) mice, with undetectable MAO-A activity and high 5-HT concentrations. MAO-A(Neo) mice showed significant increases in dendritic length in the pyramidal neurons of orbitofrontal cortex, but not basolateral amygdala, in comparison with WT littermates; by contrast, the orbitofrontal cortex of MAO-A KO mice showed significant reductions in basilar dendritic length, as well as a profound increase in apical dendritic length. MAO-A(Neo) mice showed a unique set of behavioral abnormalities, encompassing reduced open-field locomotion, perseverative responses, such as marble burying and water mist-induced grooming, and a lack of anxiety-like behaviors in the elevated plus-maze and light-dark box paradigms. Notably, whereas MAO-A(Neo) and KO mice showed significant reductions in social interaction, only the latter genotype showed increases in resident-intruder aggression. Taken together, our findings indicate that MAO A hypomorphism results in behavioral and morphological alterations distinct from those featured by MAO-A KO mice.

[Neural mechanisms of facial recognition].

PubMed

Nagai, Chiyoko

2007-01-01

We review recent researches in neural mechanisms of facial recognition in the light of three aspects: facial discrimination and identification, recognition of facial expressions, and face perception in itself. First, it has been demonstrated that the fusiform gyrus has a main role of facial discrimination and identification. However, whether the FFA (fusiform face area) is really a special area for facial processing or not is controversial; some researchers insist that the FFA is related to 'becoming an expert' for some kinds of visual objects, including faces. Neural mechanisms of prosopagnosia would be deeply concerned to this issue. Second, the amygdala seems to be very concerned to recognition of facial expressions, especially fear. The amygdala, connected with the superior temporal sulcus and the orbitofrontal cortex, appears to operate the cortical function. The amygdala and the superior temporal sulcus are related to gaze recognition, which explains why a patient with bilateral amygdala damage could not recognize only a fear expression; the information from eyes is necessary for fear recognition. Finally, even a newborn infant can recognize a face as a face, which is congruent with the innate hypothesis of facial recognition. Some researchers speculate that the neural basis of such face perception is the subcortical network, comprised of the amygdala, the superior colliculus, and the pulvinar. This network would relate to covert recognition that prosopagnosic patients have.

Loud and angry: sound intensity modulates amygdala activation to angry voices in social anxiety disorder

PubMed Central

Simon, Doerte; Becker, Michael; Mothes-Lasch, Martin; Miltner, Wolfgang H.R.

2017-01-01

Abstract Angry expressions of both voices and faces represent disorder-relevant stimuli in social anxiety disorder (SAD). Although individuals with SAD show greater amygdala activation to angry faces, previous work has failed to find comparable effects for angry voices. Here, we investigated whether voice sound-intensity, a modulator of a voice’s threat-relevance, affects brain responses to angry prosody in SAD. We used event-related functional magnetic resonance imaging to explore brain responses to voices varying in sound intensity and emotional prosody in SAD patients and healthy controls (HCs). Angry and neutral voices were presented either with normal or high sound amplitude, while participants had to decide upon the speaker’s gender. Loud vs normal voices induced greater insula activation, and angry vs neutral prosody greater orbitofrontal cortex activation in SAD as compared with HC subjects. Importantly, an interaction of sound intensity, prosody and group was found in the insula and the amygdala. In particular, the amygdala showed greater activation to loud angry voices in SAD as compared with HC subjects. This finding demonstrates a modulating role of voice sound-intensity on amygdalar hyperresponsivity to angry prosody in SAD and suggests that abnormal processing of interpersonal threat signals in amygdala extends beyond facial expressions in SAD. PMID:27651541

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

Neural foundation of human moral reasoning: an ALE meta-analysis about the role of personal perspective.

PubMed

Boccia, M; Dacquino, C; Piccardi, L; Cordellieri, P; Guariglia, C; Ferlazzo, F; Ferracuti, S; Giannini, A M

2017-02-01

Moral sense is defined as a feeling of the rightness or wrongness of an action that knowingly causes harm to people other than the agent. The large amount of data collected over the past decade allows drawing some definite conclusions about the neurobiological foundations of moral reasoning as well as a systematic investigation of methodological variables during fMRI studies. Here, we verified the existence of converging and consistent evidence in the current literature by means of a meta-analysis of fMRI studies of moral reasoning, using activation likelihood estimation meta-analysis. We also tested for a possible neural segregation as function of the perspective used during moral reasoning i.e., first or third person perspectives. Results demonstrate the existence of a wide network of areas underpinning moral reasoning, including orbitofrontal cortex, insula, amygdala, anterior cingulate cortex as well as precuneus and posterior cingulate cortex. Within this network we found a neural segregation as a function of the personal perspective, with 1PP eliciting higher activation in the bilateral insula and superior temporal gyrus as well as in the anterior cingulate cortex, lingual and fusiform gyri, middle temporal gyrus and precentral gyrus in the left hemisphere, and 3PP eliciting higher activation in the bilateral amygdala, the posterior cingulate cortex, insula and supramarginal gyrus in the left hemisphere as well as the medial and ventromedial prefrontal cortex in the right hemisphere. These results shed some more light on the contribution of these areas to moral reasoning, strongly supporting a functional specialization as a function of the perspective used during moral reasoning.

Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects.

PubMed

Goldman, Marina; Szucs-Reed, Regina P; Jagannathan, Kanchana; Ehrman, Ronald N; Wang, Ze; Li, Yin; Suh, Jesse J; Kampman, Kyle; O'Brien, Charles P; Childress, Anna Rose; Franklin, Teresa R

2013-01-01

: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. : Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. : Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). : This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.

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.

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.

Impaired spontaneous anthropomorphizing despite intact perception and social knowledge

PubMed Central

Heberlein, Andrea S.; Adolphs, Ralph

2004-01-01

Humans spontaneously imbue the world with social meaning: we see not only emotions and intentional behaviors in humans and other animals, but also anger in the movements of thunderstorms and willful sabotage in crashing computers. Converging evidence supports a role for the amygdala, a collection of nuclei in the temporal lobe, in processing emotionally and socially relevant information. Here, we report that a patient with bilateral amygdala damage described a film of animated shapes (normally seen as full of social content) in entirely asocial, geometric terms, despite otherwise normal visual perception. Control tasks showed that the impairment did not result from a global inability to describe social stimuli or a bias in language use, nor was a similar impairment observed in eight comparison subjects with damage to orbitofrontal cortex. This finding extends the role of the amygdala to the social attributions we make even to stimuli that are not explicitly social and, in so doing, suggests that the human capacity for anthropomorphizing draws on some of the same neural systems as do basic emotional responses. PMID:15123799

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

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.

A brain network instantiating approach and avoidance motivation.

PubMed

Spielberg, Jeffrey M; Miller, Gregory A; Warren, Stacie L; Engels, Anna S; Crocker, Laura D; Banich, Marie T; Sutton, Bradley P; Heller, Wendy

2012-09-01

Research indicates that dorsolateral prefrontal cortex (DLPFC) is important for pursuing goals, and areas of DLPFC are differentially involved in approach and avoidance motivation. Given the complexity of the processes involved in goal pursuit, DLPFC is likely part of a network that includes orbitofrontal cortex (OFC), cingulate, amygdala, and basal ganglia. This hypothesis was tested with regard to one component of goal pursuit, the maintenance of goals in the face of distraction. Examination of connectivity with motivation-related areas of DLPFC supported the network hypothesis. Differential patterns of connectivity suggest a distinct role for DLPFC areas, with one involved in selecting approach goals, one in selecting avoidance goals, and one in selecting goal pursuit strategies. Finally, differences in trait motivation moderated connectivity between DLPFC and OFC, suggesting that this connectivity is important for instantiating motivation. Copyright © 2012 Society for Psychophysiological Research.

A Brain Network Instantiating Approach and Avoidance Motivation

PubMed Central

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

2015-01-01

Research indicates that dorsolateral prefrontal cortex (DLPFC) is important for pursuing goals, and areas of DLPFC are differentially involved in approach and avoidance motivation. Given the complexity of the processes involved in goal pursuit, DLPFC is likely part of a network that includes orbitofrontal cortex (OFC), cingulate, amygdala, and basal ganglia. This hypothesis was tested with regard to one component of goal pursuit, the maintenance of goals in the face of distraction. Examination of connectivity with motivation-related areas of DLPFC supported the network hypothesis. Differential patterns of connectivity suggest a distinct role for DLPFC areas, with one involved in selecting approach goals, one in selecting avoidance goals, and one in selecting goal pursuit strategies. Finally, differences in trait motivation moderated connectivity between DLPFC and OFC, suggesting that this connectivity is important for instantiating motivation. PMID:22845892

The cortical response to the oral perception of fat emulsions and the effect of taster status

PubMed Central

Eldeghaidy, Sally; Marciani, Luca; McGlone, Francis; Hollowood, Tracey; Hort, Joanne; Head, Kay; Taylor, Andrew J.; Busch, Johanneke; Spiller, Robin C.; Gowland, Penny A.

2011-01-01

The rewarding attributes of foods containing fat are associated with the increase in fat consumption, but little is known of how the complex physical and chemical properties of orally ingested fats are represented and decoded in the brain nor how this impacts feeding behavior within the population. Here, functional MRI (fMRI) is used to assess the brain response to isoviscous, isosweet fat emulsions of increasing fat concentration and to investigate the correlation of behavioral and neuroimaging responses with taster status (TS). Cortical areas activated in response to fat, and those areas positively correlated with fat concentration, were identified. Significant responses that positively correlated with increasing fat concentration were found in the anterior insula, frontal operculum and secondary somatosensory cortex (SII), anterior cingulate cortex, and amygdala. Assessing the effect of TS revealed a strong correlation with self-reported preference of the samples and with cortical response in somatosensory areas [primary somatosensory cortex (SI), SII, and midinsula] and the primary taste area (anterior insula) and a trend in reward areas (amygdala and orbitofrontal cortex). This finding of a strong correlation with TS in somatosensory areas supports the theory of increased mechanosensory trigeminal innervation in high 6-n-propyl-2-thiouracil (PROP) tasters and has been linked to a higher risk of obesity. The interindividual differences in blood oxygenation level-dependent (BOLD) amplitude with TS indicates that segmenting populations by TS will reduce the heterogeneity of BOLD responses, improving signal detection power. PMID:21389303

Cellular activation in limbic brain systems during social play behaviour in rats

PubMed Central

van Kerkhof, Linda W.M.; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J.M.J.

2013-01-01

Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-fos as a marker. After a session of social play behaviour, pronounced increases in c-fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organised in this network, as indicated by play-specific correlations in c-fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organised neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats. PMID:23670540

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

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.

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

Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex.

PubMed

Takahashi, Yuji K; Roesch, Matthew R; Wilson, Robert C; Toreson, Kathy; O'Donnell, Patricio; Niv, Yael; Schoenbaum, Geoffrey

2011-10-30

The orbitofrontal cortex has been hypothesized to carry information regarding the value of expected rewards. Such information is essential for associative learning, which relies on comparisons between expected and obtained reward for generating instructive error signals. These error signals are thought to be conveyed by dopamine neurons. To test whether orbitofrontal cortex contributes to these error signals, we recorded from dopamine neurons in orbitofrontal-lesioned rats performing a reward learning task. Lesions caused marked changes in dopaminergic error signaling. However, the effect of lesions was not consistent with a simple loss of information regarding expected value. Instead, without orbitofrontal input, dopaminergic error signals failed to reflect internal information about the impending response that distinguished externally similar states leading to differently valued future rewards. These results are consistent with current conceptualizations of orbitofrontal cortex as supporting model-based behavior and suggest an unexpected role for this information in dopaminergic error signaling.

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.

The Neural Correlates of Emotion Regulation by Implementation Intentions

PubMed Central

Hallam, Glyn P.; Webb, Thomas L.; Sheeran, Paschal; Miles, Eleanor; Wilkinson, Iain D.; Hunter, Michael D.; Barker, Anthony T.; Woodruff, Peter W. R.; Totterdell, Peter; Lindquist, Kristen A.; Farrow, Tom F. D.

2015-01-01

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency. PMID:25798822

The CB1 Neutral Antagonist Tetrahydrocannabivarin Reduces Default Mode Network and Increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.

PubMed

Rzepa, Ewelina; Tudge, Luke; McCabe, Ciara

2015-09-10

The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions. © The Author 2015. Published by Oxford University Press on behalf of CINP.

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.

Loud and angry: sound intensity modulates amygdala activation to angry voices in social anxiety disorder.

PubMed

Simon, Doerte; Becker, Michael; Mothes-Lasch, Martin; Miltner, Wolfgang H R; Straube, Thomas

2017-03-01

Angry expressions of both voices and faces represent disorder-relevant stimuli in social anxiety disorder (SAD). Although individuals with SAD show greater amygdala activation to angry faces, previous work has failed to find comparable effects for angry voices. Here, we investigated whether voice sound-intensity, a modulator of a voice's threat-relevance, affects brain responses to angry prosody in SAD. We used event-related functional magnetic resonance imaging to explore brain responses to voices varying in sound intensity and emotional prosody in SAD patients and healthy controls (HCs). Angry and neutral voices were presented either with normal or high sound amplitude, while participants had to decide upon the speaker's gender. Loud vs normal voices induced greater insula activation, and angry vs neutral prosody greater orbitofrontal cortex activation in SAD as compared with HC subjects. Importantly, an interaction of sound intensity, prosody and group was found in the insula and the amygdala. In particular, the amygdala showed greater activation to loud angry voices in SAD as compared with HC subjects. This finding demonstrates a modulating role of voice sound-intensity on amygdalar hyperresponsivity to angry prosody in SAD and suggests that abnormal processing of interpersonal threat signals in amygdala extends beyond facial expressions in SAD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The Central Amygdala Nucleus is Critical for Incubation of Methamphetamine Craving

PubMed Central

Li, Xuan; Zeric, Tamara; Kambhampati, Sarita; Bossert, Jennifer M; Shaham, Yavin

2015-01-01

Cue-induced methamphetamine seeking progressively increases after withdrawal but mechanisms underlying this ‘incubation of methamphetamine craving' are unknown. Here we studied the role of central amygdala (CeA), ventral medial prefrontal cortex (vmPFC), and orbitofrontal cortex (OFC), brain regions implicated in incubation of cocaine and heroin craving, in incubation of methamphetamine craving. We also assessed the role of basolateral amygdala (BLA) and dorsal medial prefrontal cortex (dmPFC). We trained rats to self-administer methamphetamine (10 days; 9 h/day, 0.1 mg/kg/infusion) and tested them for cue-induced methamphetamine seeking under extinction conditions during early (2 days) or late (4–5 weeks) withdrawal. We first confirmed that ‘incubation of methamphetamine craving' occurs under our experimental conditions. Next, we assessed the effect of reversible inactivation of CeA or BLA by GABAA+GABAB receptor agonists (muscimol+baclofen, 0.03+0.3 nmol) on cue-induced methamphetamine seeking during early and late withdrawal. We also assessed the effect of muscimol+baclofen reversible inactivation of vmPFC, dmPFC, and OFC on ‘incubated' cue-induced methamphetamine seeking during late withdrawal. Lever presses in the cue-induced methamphetamine extinction tests were higher during late withdrawal than during early withdrawal (incubation of methamphetamine craving). Muscimol+baclofen injections into CeA but not BLA decreased cue-induced methamphetamine seeking during late but not early withdrawal. Muscimol+baclofen injections into dmPFC, vmPFC, or OFC during late withdrawal had no effect on incubated cue-induced methamphetamine seeking. Together with previous studies, results indicate that the CeA has a critical role in incubation of both drug and non-drug reward craving and demonstrate an unexpected dissociation in mechanisms of incubation of methamphetamine vs cocaine craving. PMID:25475163

Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder.

PubMed

Månsson, Kristoffer N T; Carlbring, Per; Frick, Andreas; Engman, Jonas; Olsson, Carl-Johan; Bodlund, Owe; Furmark, Tomas; Andersson, Gerhard

2013-12-30

Randomized controlled trials have yielded promising results for internet-delivered cognitive behavior therapy (iCBT) for patients with social anxiety disorder (SAD). The present study investigated anxiety-related neural changes after iCBT for SAD. The amygdala is a critical hub in the neural fear network, receptive to change using emotion regulation strategies and a putative target for iCBT. Twenty-two subjects were included in pre- and post-treatment functional magnetic resonance imaging at 3T assessing neural changes during an affective face processing task. Treatment outcome was assessed using social anxiety self-reports and the Clinical Global Impression-Improvement (CGI-I) scale. ICBT yielded better outcome than ABM (66% vs. 25% CGI-I responders). A significant differential activation of the left amygdala was found with relatively decreased reactivity after iCBT. Changes in the amygdala were related to a behavioral measure of social anxiety. Functional connectivity analysis in the iCBT group showed that the amygdala attenuation was associated with increased activity in the medial orbitofrontal cortex and decreased activity in the right ventrolateral and dorsolateral (dlPFC) cortices. Treatment-induced neural changes with iCBT were consistent with previously reported studies on regular CBT and emotion regulation in general. Copyright © 2013 Elsevier Ireland Ltd. 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).

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

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.

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.

Avoidant Responses to Interpersonal Provocation Are Associated with Increased Amygdala and Decreased Mentalizing Network Activity

PubMed Central

Krämer, Ulrike M.

2017-01-01

When intentionally pushed or insulted, one can either flee from the provoker or retaliate. The implementation of such fight-or-flight decisions is a central aspect in the genesis and evolution of aggression episodes, yet it is usually investigated only indirectly or in nonsocial situations. In the present fMRI study, we aimed to distinguish brain regions associated with aggressive and avoidant responses to interpersonal provocation in humans. Participants (thirty-six healthy young women) could either avoid or face a highly (HP) and a lowly (LP) provoking opponent in a competitive reaction time task: the fight-or-escape (FOE) paradigm. Subjects avoided the HP more often, but retaliated when facing her. Moreover, they chose to fight the HP more quickly, and showed increased heart rate (HR) right before confronting her. Orbitofrontal cortex (OFC) and sensorimotor cortex were more active when participants decided to fight, whereas the mentalizing network was engaged when deciding to avoid. Importantly, avoiding the HP relative to the LP was associated with both higher activation in the right basolateral amygdala and lower relative activity in several mentalizing regions [e.g., medial and inferior frontal gyrus (IFG), temporal-parietal junction (TPJ)]. These results suggest that avoidant responses to provocation might result from heightened threat anticipation and are associated with reduced perspective taking. Furthermore, our study helps to reconcile conflicting findings on the role of the mentalizing network, the amygdala, and the OFC in aggression. PMID:28660251

A cortical network model of cognitive and emotional influences in human decision making.

PubMed

Nazir, Azadeh Hassannejad; Liljenström, Hans

2015-10-01

Decision making (DM)(2) is a complex process that appears to involve several brain structures. In particular, amygdala, orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) seem to be essential in human decision making, where both emotional and cognitive aspects are taken into account. In this paper, we present a computational network model representing the neural information processing of DM, from perception to behavior. We model the population dynamics of the three neural structures (amygdala, OFC and LPFC), as well as their interaction. In our model, the neurodynamic activity of amygdala and OFC represents the neural correlates of secondary emotion, while the activity of certain neural populations in OFC alone represents the outcome expectancy of different options. The cognitive/rational aspect of DM is associated with LPFC. Our model is intended to give insights on the emotional and cognitive processes involved in DM under various internal and external contexts. Different options for actions are represented by the oscillatory activity of cell assemblies, which may change due to experience and learning. Knowledge and experience of the outcome of our decisions and actions can eventually result in changes in our neural structures, attitudes and behaviors. Simulation results may have implications for how we make decisions for our individual actions, as well as for societal choices, where we take examples from transport and its impact on CO2 emissions and climate change. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

PubMed

Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

2016-12-01

Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

Neural responses to fearful eyes in children with conduct problems and varying levels of callous-unemotional traits.

PubMed

Sebastian, C L; McCrory, E J; Dadds, M R; Cecil, C A M; Lockwood, P L; Hyde, Z H; De Brito, S A; Viding, E

2014-01-01

Children with conduct problems (CP) are a heterogeneous group. Those with high levels of callous-unemotional traits (CP/HCU) appear emotionally under-reactive at behavioural and neural levels whereas those with low levels of CU traits (CP/LCU) appear emotionally over-reactive, compared with typically developing (TD) controls. Investigating the degree to which these patterns of emotional reactivity are malleable may have important translational implications. Instructing participants with CP/HCU to focus on the eyes of fearful faces (i.e. the most salient feature) can ameliorate their fear-recognition deficits, but it is unknown whether this is mediated by amygdala response. It is also unknown whether focusing on fearful eyes is associated with increased amygdala reactivity in CP/LCU. Functional magnetic resonance imaging (fMRI) was used to measure neural responses to fearful and calm faces in children with CP/HCU, CP/LCU and TD controls (n = 17 per group). On half of trials participants looked for a blue dot anywhere within target faces; on the other half, participants were directed to focus on the eye region. Reaction time (RT) data showed that CP/LCU were selectively slowed in the fear/eyes condition. For the same condition, CP/LCU also showed increased amygdala and subgenual anterior cingulate cortex (sgACC)/orbitofrontal cortex (OFC) responses compared with TD controls. RT and amygdala response to fear/eyes were correlated in CP/LCU only. No effects of focusing on the eye region were observed in CP/HCU. These data extend the evidence base suggesting that CU traits index meaningful heterogeneity in conduct problems. Focusing on regulating reactive emotional responses may be a fruitful strategy for children with CP/LCU.

Sex Differences in the Neural Correlates of Autonomic Arousal: A Pilot PET Study

PubMed Central

Nugent, Allison C.; Bain, Earle E.; Thayer, Julian F.; Sollers, John J.; Drevets, Wayne C.

2011-01-01

Electrophysiology, behavioral, and neuroimaging studies have revealed sex-related differences in autonomic cardiac control, as reflected in measurements of heart rate variability (HRV). Imaging studies indicate that the neurobiological correlates of autonomic nervous system (ANS) function can be investigated by measuring indices of HRV during the performance of mildly strenuous motor tasks or mildly stressful cognitive tasks. In this preliminary study, fifteen male and seven female healthy subjects underwent H215O-positron emission tomography (PET) and electrocardiograph (ECG) recording while performing a handgrip motor task and an n-back task. Indices of HRV were calculated and correlated with regional cerebral blood flow (rCBF). We hypothesized that sex differences would be evident in brain regions known to participate in autonomic regulation: the anterior insula, the anterior cingulate cortex, the orbitofrontal cortex, and the amygdala. Our study found that associations between rCBF and parasympathetic indices differed significantly between female and male subjects in the amygdala. Females showed a positive correlation between rCBF and parasympathetic indices while males exhibited negative correlations. This differential correlation of amygdala rCBF and parasympathetic activity between males and females may reflect differences in parasympathetic/sympathetic balance between sexes, consistent with known sexual dimorphism in the amygdala and closely related structures such as the hypothalamus. These preliminary imaging results are consistent with earlier reports of significant correlation between brain activity and HRV, and extend these findings by demonstrating prominent sex differences in the neural control of the ANS. While the generalizability of our results was limited by the small size of the study samples, the relatively robust effect size of the differences found between groups encourages further work in larger samples to characterize sex differences in the neural correlates of autonomic arousal. PMID:21414364

Opponent appetitive-aversive neural processes underlie predictive learning of pain relief.

PubMed

Seymour, Ben; O'Doherty, John P; Koltzenburg, Martin; Wiech, Katja; Frackowiak, Richard; Friston, Karl; Dolan, Raymond

2005-09-01

Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.

Neural correlates of maintaining one's political beliefs in the face of counterevidence.

PubMed

Kaplan, Jonas T; Gimbel, Sarah I; Harris, Sam

2016-12-23

People often discount evidence that contradicts their firmly held beliefs. However, little is known about the neural mechanisms that govern this behavior. We used neuroimaging to investigate the neural systems involved in maintaining belief in the face of counterevidence, presenting 40 liberals with arguments that contradicted their strongly held political and non-political views. Challenges to political beliefs produced increased activity in the default mode network-a set of interconnected structures associated with self-representation and disengagement from the external world. Trials with greater belief resistance showed increased response in the dorsomedial prefrontal cortex and decreased activity in the orbitofrontal cortex. We also found that participants who changed their minds more showed less BOLD signal in the insula and the amygdala when evaluating counterevidence. These results highlight the role of emotion in belief-change resistance and offer insight into the neural systems involved in belief maintenance, motivated reasoning, and related phenomena.

Emergent processes in cognitive-emotional interactions

PubMed Central

Pessoa, Luiz

2010-01-01

Emotion and cognition have been viewed as largely separate entities in the brain. Within this framework, significant progress has been made in understanding specific aspects of behavior. Research in the past two decades, however, has started to paint a different picture of brain organization, one in which network interactions are key to understanding complex behaviors. From both basic and clinical perspectives, the characterization of cognitive-emotional interactions constitutes a fundamental issue in the investigation of the mind and brain. This review will highlight the interactive and integrative potential that exists in the brain to bring together the cognitive and emotional domains. First, anatomical evidence will be provided, focusing on structures such as hypothalamus, basal forebrain, amygdala, cingulate cortex, orbitofrontal cortex, and insula. Data on functional interactions will then be discussed, followed by a discussion of a dual competition framework, which describes cognitive-emotional interactions in terms of perceptual and cognitive competition mechanisms. PMID:21319489

Neural correlates of maintaining one’s political beliefs in the face of counterevidence

PubMed Central

Kaplan, Jonas T.; Gimbel, Sarah I.; Harris, Sam

2016-01-01

People often discount evidence that contradicts their firmly held beliefs. However, little is known about the neural mechanisms that govern this behavior. We used neuroimaging to investigate the neural systems involved in maintaining belief in the face of counterevidence, presenting 40 liberals with arguments that contradicted their strongly held political and non-political views. Challenges to political beliefs produced increased activity in the default mode network—a set of interconnected structures associated with self-representation and disengagement from the external world. Trials with greater belief resistance showed increased response in the dorsomedial prefrontal cortex and decreased activity in the orbitofrontal cortex. We also found that participants who changed their minds more showed less BOLD signal in the insula and the amygdala when evaluating counterevidence. These results highlight the role of emotion in belief-change resistance and offer insight into the neural systems involved in belief maintenance, motivated reasoning, and related phenomena. PMID:28008965

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

Neural predictors of substance use disorders in Young adulthood.

PubMed

O'Brien, Jessica W; Hill, Shirley Y

2017-10-30

Offspring from multiplex, alcohol-dependent families are at heightened risk for substance use disorders (SUDs) in adolescence and young adulthood. These high-risk offspring have also been shown to have atypical structure and function of brain regions implicated in emotion regulation, social cognition, and reward processing. This study assessed the relationship between amygdala and orbitofrontal cortex (OFC) volumes obtained in adolescence and SUD outcomes in young adulthood among high-risk offspring and low-risk controls. A total of 78 participants (40 high-risk; 38 low-risk) from a longitudinal family study, ages 8-19, underwent magnetic resonance imaging; volumes of the amygdala and OFC were obtained with manual tracing. SUD outcomes were assessed at approximately yearly intervals. Cox regression survival analyses were used to assess the effect of regional brain volumes on SUD outcomes. The ratio of OFC to amygdala volume significantly predicted SUD survival time across the sample; reduction in survival time was seen in those with smaller ratios for both high-risk and low-risk groups. Morphology of prefrontal relative to limbic regions in adolescence prospectively predicts age of onset for substance use disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Neural abnormalities in early-onset and adolescence-onset conduct disorder.

PubMed

Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

2010-07-01

Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.

PubMed

Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng

2016-12-01

The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression. © 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.

Association between brain structure and phenotypic characteristics in pedophilia.

PubMed

Poeppl, Timm B; Nitschke, Joachim; Santtila, Pekka; Schecklmann, Martin; Langguth, Berthold; Greenlee, Mark W; Osterheider, Michael; Mokros, Andreas

2013-05-01

Studies applying structural neuroimaging to pedophiles are scarce and have shown conflicting results. Although first findings suggested reduced volume of the amygdala, pronounced gray matter decreases in frontal regions were observed in another group of pedophilic offenders. When compared to non-sexual offenders instead of community controls, pedophiles revealed deficiencies in white matter only. The present study sought to test the hypotheses of structurally compromised prefrontal and limbic networks and whether structural brain abnormalities are related to phenotypic characteristics in pedophiles. We compared gray matter volume of male pedophilic offenders and non-sexual offenders from high-security forensic hospitals using voxel-based morphometry in cross-sectional and correlational whole-brain analyses. The significance threshold was set to p < .05, corrected for multiple comparisons. Compared to controls, pedophiles exhibited a volume reduction of the right amygdala (small volume corrected). Within the pedophilic group, pedosexual interest and sexual recidivism were correlated with gray matter decrease in the left dorsolateral prefrontal cortex (r = -.64) and insular cortex (r = -.45). Lower age of victims was strongly associated with gray matter reductions in the orbitofrontal cortex (r = .98) and angular gyri bilaterally (r = .70 and r = .93). Our findings of specifically impaired neural networks being related to certain phenotypic characteristics might account for the heterogeneous results in previous neuroimaging studies of pedophilia. The neuroanatomical abnormalities in pedophilia seem to be of a dimensional rather than a categorical nature, supporting the notion of a multifaceted disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Role of the Orbitofrontal Cortex in Normally Developing Compulsive-Like Behaviors and Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Evans, David W.; Lewis, Marc D.; Iobst, Emily

2004-01-01

Mounting evidence concerning obsessive-compulsive disorders points to abnormal functioning of the orbitofrontal cortices. First, patients with obsessive-compulsive disorder (OCD) perform poorly on tasks that rely on response suppression/motor inhibition functions mediated by the orbitofrontal cortex relative to both normal and clinical controls.…

Quetiapine modulates functional connectivity in brain aggression networks.

PubMed

Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

2013-07-15

Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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.

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.

Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives

PubMed Central

Kanske, P; Schönfelder, S; Forneck, J; Wessa, M

2015-01-01

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD. PMID:25603413

Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers.

PubMed

Oberlin, Brandon G; Dzemidzic, Mario; Bragulat, Veronique; Lehigh, Cari A; Talavage, Thomas; O'Connor, Sean J; Kareken, David A

2012-03-01

Antisocial traits are common among alcoholics- particularly in certain subtypes. Although people with antisocial tendencies show atypical brain activation in some emotion and reward paradigms, how the brain reward systems of heavy drinkers (HD) are influenced by antisocial traits remains unclear. We used subjects' preferred alcohol drink odors (AO), appetitive (ApCO) and non-appetitive (NApO) control odors in functional magnetic resonance imaging (fMRI) to determine if reward system responses varied as a function of antisocial trait density (ASD). In this retrospective analysis, we examined 30 HD who had participated in imaging twice: once while exposed to clamped intravenous alcohol infusion targeted to 50mg%, and once during placebo saline infusion. Under placebo, there were positive correlations between ASD and blood oxygenation level dependent (BOLD) activation in the [AO>ApCO] contrast in the left dorsal putamen, while negative correlations were present in medial orbitofrontal cortex (OFC) and the bilateral amygdala. A similar pattern was observed in the correlation with the [AO>NApO] contrast. This inverse relationship between ASD and activation in OFC and amygdala was specific to AO. However, negative correlations between ASD and the [ApCO>NApO] contrast were also present in the insula, putamen, and medial frontal cortex. These data suggest that frontal and limbic reward circuits of those with significant ASD are less responsive to reward cues in general, and particularly to alcohol cues in medial OFC and amygdala. These findings are broadly consistent with the reward deficiency syndrome hypothesis, although positive correlation in the striatum suggests regional variability. Copyright © 2011 Elsevier Inc. All rights reserved.

Multiple "buy buttons" in the brain: Forecasting chocolate sales at point-of-sale based on functional brain activation using fMRI.

PubMed

Kühn, Simone; Strelow, Enrique; Gallinat, Jürgen

2016-08-01

We set out to forecast consumer behaviour in a supermarket based on functional magnetic resonance imaging (fMRI). Data was collected while participants viewed six chocolate bar communications and product pictures before and after each communication. Then self-reports liking judgement were collected. fMRI data was extracted from a priori selected brain regions: nucleus accumbens, medial orbitofrontal cortex, amygdala, hippocampus, inferior frontal gyrus, dorsomedial prefrontal cortex assumed to contribute positively and dorsolateral prefrontal cortex and insula were hypothesized to contribute negatively to sales. The resulting values were rank ordered. After our fMRI-based forecast an instore test was conducted in a supermarket on n=63.617 shoppers. Changes in sales were best forecasted by fMRI signal during communication viewing, second best by a comparison of brain signal during product viewing before and after communication and least by explicit liking judgements. The results demonstrate the feasibility of applying neuroimaging methods in a relatively small sample to correctly forecast sales changes at point-of-sale. Copyright © 2016. Published by Elsevier Inc.

Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies

PubMed Central

Liu, Xun; Hairston, Jacqueline; Schrier, Madeleine; Fan, Jin

2011-01-01

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior (ACC) and posterior (PCC) cingulate cortex, as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore distributed and interrelated representations of reward valuation and valence assessment into account. PMID:21185861

Impairment in judgement of the moral emotion guilt following orbitofrontal cortex damage.

PubMed

Funayama, Michitaka; Koreki, Akihiro; Muramatsu, Taro; Mimura, Masaru; Kato, Motoichiro; Abe, Takayuki

2018-04-19

Although neuroimaging studies have provided evidence for an association between moral emotions and the orbitofrontal cortex, studies on patients with focal lesions using experimental probes of moral emotions are scarce. Here, we addressed this topic by presenting a moral emotion judgement task to patients with focal brain damage. Four judgement tasks in a simple pairwise choice paradigm were given to 72 patients with cerebrovascular disease. These tasks consisted of a perceptual line judgement task as a control task; the objects' preference task as a basic preference judgement task; and two types of moral emotion judgement task, an anger task and a guilt task. A multiple linear regression analysis was performed on each set of task performance scores to take into account potential confounders. Performance on the guilt emotion judgement task negatively correlated with the orbitofrontal cortex damage, but not with the other variables. Results for the other judgement tasks did not reach statistical significance. The close association between orbitofrontal cortex damage and a decrease in guilt emotion judgement consistency might suggest that the orbitofrontal cortex plays a key role in the sense of guilt, a hallmark of morality. © 2018 The British Psychological Society.

Clinically Anxious Individuals Show Disrupted Feedback between Inferior Frontal Gyrus and Prefrontal-Limbic Control Circuit.

PubMed

Cha, Jiook; DeDora, Daniel; Nedic, Sanja; Ide, Jaime; Greenberg, Tsafrir; Hajcak, Greg; Mujica-Parodi, Lilianne Rivka

2016-04-27

Clinical anxiety is associated with generalization of conditioned fear, in which innocuous stimuli elicit alarm. Using Pavlovian fear conditioning (electric shock), we quantify generalization as the degree to which subjects' neurobiological responses track perceptual similarity gradients to a conditioned stimulus. Previous studies show that the ventromedial prefrontal cortex (vmPFC) inversely and ventral tegmental area directly track the gradient of perceptual similarity to the conditioned stimulus in healthy individuals, whereas clinically anxious individuals fail to discriminate. Here, we extend this work by identifying specific functional roles within the prefrontal-limbic circuit. We analyzed fMRI time-series acquired from 57 human subjects during a fear generalization task using entropic measures of circuit-wide regulation and feedback (power spectrum scale invariance/autocorrelation), in combination with structural (diffusion MRI-probabilistic tractography) and functional (stochastic dynamic causal modeling) measures of prefrontal-limbic connectivity within the circuit. Group comparison and correlations with anxiety severity across 57 subjects revealed dysregulatory dynamic signatures within the inferior frontal gyrus (IFG), which our prior work has linked to impaired feedback within the circuit. Bayesian model selection then identified a fully connected prefrontal-limbic model comprising the IFG, vmPFC, and amygdala. Dysregulatory IFG dynamics were associated with weaker reciprocal excitatory connectivity between the IFG and the vmPFC. The vmPFC exhibited inhibitory influence on the amygdala. Our current results, combined with our previous work across a threat-perception spectrum of 137 subjects and a meta-analysis of 366 fMRI studies, dissociate distinct roles for three prefrontal-limbic regions, wherein the IFG provides evaluation of stimulus meaning, which then informs the vmPFC in inhibiting the amygdala. Affective neuroscience has generally treated prefrontal regions (orbitofrontal cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex) equivalently as inhibitory components of the prefrontal-limbic system. Yet research across the anxiety spectrum suggests that the inferior frontal gyrus may have a more complex role in emotion regulation, as this region shows abnormal function in disorders of both hyperarousal and hypoarousal. Using entropic measures of circuit-wide regulation and feedback, in combination with measures of structural and functional connectivity, we dissociate distinct roles for three prefrontal-limbic regions, wherein the inferior frontal gyrus provides evaluation of stimulus meaning, which then informs the ventromedial prefrontal cortex in inhibiting the amygdala. This reconfiguration coheres with studies of conceptual disambiguation also implicating the inferior frontal gyrus. Copyright © 2016 the authors 0270-6474/16/364708-11$15.00/0.

Neuroimaging in autism spectrum disorders: 1H-MRS and NIRS study.

PubMed

Mori, Kenji; Toda, Yoshihiro; Ito, Hiromichi; Mori, Tatsuo; Mori, Keiko; Goji, Aya; Hashimoto, Hiroko; Tani, Hiroe; Miyazaki, Masahito; Harada, Masafumi; Kagami, Shoji

2015-01-01

Using proton magnetic resonance spectroscopy ((1)H-MRS), we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC) in children with autism spectrum disorders (ASD). The concentrations of N-acetylaspartate (NAA) in these regions of ASD were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in ASD. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of ASD. We performed a near-infrared spectroscopy (NIRS) study to evaluate the mirror neuron system in children with ASD. The concentrations of oxygenated hemoglobin (oxy-Hb) were measured with frontal probes using a 34-channel NIRS machine while the subjects imitated emotional facial expressions. The increments in the concentration of oxy-Hb in the pars opercularis of the inferior frontal gyrus in autistic subjects were significantly lower than those in the controls. However, the concentrations of oxy-Hb in this area were significantly elevated in autistic subjects after they were trained to imitate emotional facial expressions. The results suggest that mirror neurons could be activated by repeated imitation in children with ASD.

Prefrontal-limbic connectivity during worry in older adults with generalized anxiety disorder.

PubMed

Mohlman, Jan; Eldreth, Dana A; Price, Rebecca B; Staples, Alison M; Hanson, Catherine

2017-04-01

Although generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders in older adults, very little is known about the neurobiology of worry, the hallmark symptom of GAD in adults over the age of 60. This study investigated the neurobiology and neural circuitry of worry in older GAD patients and controls. Twenty older GAD patients and 16 age-matched controls (mean age = 67.88) were compared on clinical measures and neural activity during worry using functional magnetic resonance imaging. As expected, worry elicited activation in frontal regions, amygdala, and insula within the GAD group, with a similar but less prominent frontal pattern was observed in controls. Effective connectivity analyses revealed a positive directional circuit in the GAD group extending from ventromedial through dorsolateral prefrontal cortices, converging on the amygdala. A less complex circuit was observed in controls with only dorsolateral prefrontal regions converging on the amygdala; however, a separate circuit passing through the orbitofrontal cortex converged on the insula. Results elucidate a different neurobiology of pathological versus normal worry in later life. A limited resource model is implicated wherein worry in GAD competes for the same neural resources (e.g. prefrontal cortical areas) that are involved in the adaptive regulation of emotion through cognitive and behavioral strategies.

Psychopathic traits are associated with cortical and subcortical volume alterations in healthy individuals

PubMed Central

Ferreira-Santos, Fernando; Almeida, Pedro R.; Barbosa, Fernando; Marques-Teixeira, João; Marsh, Abigail A.

2015-01-01

Research suggests psychopathy is associated with structural brain alterations that may contribute to the affective and interpersonal deficits frequently observed in individuals with high psychopathic traits. However, the regional alterations related to different components of psychopathy are still unclear. We used voxel-based morphometry to characterize the structural correlates of psychopathy in a sample of 35 healthy adults assessed with the Triarchic Psychopathy Measure. Furthermore, we examined the regional grey matter alterations associated with the components described by the triarchic model. Our results showed that, after accounting for variation in total intracranial volume, age and IQ, overall psychopathy was negatively associated with grey matter volume in the left putamen and amygdala. Additional regression analysis with anatomical regions of interests revealed total triPM score was also associated with increased lateral orbitofrontal cortex (OFC) and caudate volume. Boldness was positively associated with volume in the right insula. Meanness was positively associated with lateral OFC and striatum volume, and negatively associated with amygdala volume. Finally, disinhibition was negatively associated with amygdala volume. Results highlight the contribution of both subcortical and cortical brain alterations for subclinical psychopathy and are discussed in light of prior research and theoretical accounts about the neurobiological bases of psychopathic traits. PMID:25971600

Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits.

PubMed

Finger, Elizabeth Carrie; Marsh, Abigail; Blair, Karina Simone; Majestic, Catherine; Evangelou, Iordanis; Gupta, Karan; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Tovar-Moll, Fernanda; Pine, Daniel; Blair, Robert James

2012-06-30

Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Lateralized interactive social content and valence processing within the human amygdala

PubMed Central

Vrtička, Pascal; Sander, David; Vuilleumier, Patrik

2013-01-01

In the past, the amygdala has generally been conceptualized as a fear-processing module. Recently, however, it has been proposed to respond to all stimuli that are relevant with respect to the current needs, goals, and values of an individual. This raises the question of whether the human amygdala may differentiate between separate kinds of relevance. A distinction between emotional (vs. neutral) and social (vs. non-social) relevance is supported by previous studies showing that the human amygdala preferentially responds to both emotionally and socially significant information, and these factors might even display interactive encoding properties. However, no investigation has yet probed a full 2 (positive vs. negative valence) × 2 (social vs. non-social content) processing pattern, with neutral images as an additional baseline. Applying such an extended orthogonal factorial design, our fMRI study demonstrates that the human amygdala is (1) more strongly activated for neutral social vs. non-social information, (2) activated at a similar level when viewing social positive or negative images, but (3) displays a valence effect (negative vs. positive) for non-social images. In addition, this encoding pattern is not influenced by cognitive or behavioral emotion regulation mechanisms, and displays a hemispheric lateralization with more pronounced effects on the right side. Finally, the same valence × social content interaction was found in three additional cortical regions, namely the right fusiform gyrus, right anterior superior temporal gyrus, and medial orbitofrontal cortex. Overall, these findings suggest that valence and social content processing represent distinct kinds of relevance that interact within the human amygdala as well as in a more extensive cortical network, likely subserving a key role in relevance detection. PMID:23346054

Investigating the neural correlates of smoking: Feasibility and results of combining electronic cigarettes with fMRI.

PubMed

Wall, Matthew B; Mentink, Alexander; Lyons, Georgina; Kowalczyk, Oliwia S; Demetriou, Lysia; Newbould, Rexford D

2017-09-12

Cigarette addiction is driven partly by the physiological effects of nicotine, but also by the distinctive sensory and behavioural aspects of smoking, and understanding the neural effects of such processes is vital. There are many practical difficulties associated with subjects smoking in the modern neuroscientific laboratory environment, however electronic cigarettes obviate many of these issues, and provide a close simulation of smoking tobacco cigarettes. We have examined the neural effects of 'smoking' electronic cigarettes with concurrent functional Magnetic Resonance Imaging (fMRI). The results demonstrate the feasibility of using these devices in the MRI environment, and show brain activation in a network of cortical (motor cortex, insula, cingulate, amygdala) and sub-cortical (putamen, thalamus, globus pallidus, cerebellum) regions. Concomitant relative deactivations were seen in the ventral striatum and orbitofrontal cortex. These results reveal the brain processes involved in (simulated) smoking for the first time, and validate a novel approach to the study of smoking, and addiction more generally.

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.

Orbito-frontal cortex and thalamus volumes in the patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

PubMed

Atmaca, Murad; Yildirim, Hanefi; Yilmaz, Seda; Caglar, Neslihan; Mermi, Osman; Korkmaz, Sevda; Akaslan, Unsal; Gurok, M Gurkan; Kekilli, Yasemin; Turkcapar, Hakan

2018-07-01

Background The effect of a variety of treatment modalities including psychopharmacological and cognitive behavioral therapy on the brain volumes and neurochemicals have not been investigated enough in the patients with obsessive-compulsive disorder. Therefore, in the present study, we aimed to investigate the effect of cognitive behavioral therapy on the volumes of the orbito-frontal cortex and thalamus regions which seem to be abnormal in the patients with obsessive-compulsive disorder. We hypothesized that there would be change in the volumes of the orbito-frontal cortex and thalamus. Methods Twelve patients with obsessive-compulsive disorder and same number of healthy controls were included into the study. At the beginning of the study, the volumes of the orbito-frontal cortex and thalamus were compared by using magnetic resonance imaging. In addition, volumes of these regions were measured before and after the cognitive behavioral therapy treatment in the patient group. Results The patients with obsessive-compulsive disorder had greater left and right thalamus volumes and smaller left and right orbito-frontal cortex volumes compared to those of healthy control subjects at the beginning of the study. When we compared baseline volumes of the patients with posttreatment ones, we detected that thalamus volumes significantly decreased throughout the period for both sides and that the orbito-frontal cortex volumes significantly increased throughout the period for only left side. Conclusions In summary, we found that cognitive behavioral therapy might volumetrically affect the key brain regions involved in the neuroanatomy of obsessive-compulsive disorder. However, future studies with larger sample are required.

Brain Hypoactivation, Autonomic Nervous System Dysregulation, and Gonadal Hormones in Depression: A Preliminary Study

PubMed Central

Holsen, Laura M.; Lee, Jong-Hwan; Spaeth, Sarah B.; Ogden, Lauren A.; Klibanski, Anne; Whitfield-Gabrieli, Susan; Sloan, Richard P.; Goldstein, Jill M.

2012-01-01

The comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus, understanding the co-occurrence of these disorders will have major public health significance. MDD is associated with an abnormal stress response, manifested in brain circuitry deficits, gonadal dysfunction, and autonomic nervous system (ANS) dysregulation. Contribution of the relationships between these systems to the pathophysiology of MDD is not well understood. The objective of this preliminary study was to investigate, in parallel, relationships between HPG-axis functioning, stress response circuitry activation, and parasympathetic reactivity in healthy controls and women with MDD. Using fMRI with pulse oximetry [from which we calculated the high frequency (HF) component of R-R interval variability (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied eight women with recurrent MDD in remission and six controls during a stress response paradigm. We demonstrated that hypoactivations of hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and subgenual ACC were associated with lower parasympathetic cardiac modulation in MDD women. Estradiol and progesterone attenuated group differences in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and OFC in MDD women. Findings have implications for understanding the relationship between mood, arousal, heart regulation, and gonadal hormones, and may provide insights into MDD and CVD risk comorbidity. PMID:22395084

Distinct neural systems underlying reduced emotional enhancement for positive and negative stimuli in early Alzheimer's disease

PubMed Central

Mistridis, Panagiota; Taylor, Kirsten I.; Kissler, Johanna M.; Monsch, Andreas U.; Kressig, Reto W.; Kivisaari, Sasa L.

2014-01-01

Emotional information is typically better remembered than neutral content, and previous studies suggest that this effect is subserved particularly by the amygdala together with its interactions with the hippocampus. However, it is not known whether amygdala damage affects emotional memory performance at immediate and delayed recall, and whether its involvement is modulated by stimulus valence. Moreover, it is unclear to what extent more distributed neocortical regions involved in e.g., autobiographical memory, also contribute to emotional processing. We investigated these questions in a group of patients with Alzheimer's disease (AD), which affects the amygdala, hippocampus and neocortical regions. Healthy controls (n = 14), patients with AD (n = 15) and its putative prodrome amnestic mild cognitive impairment (n = 11) completed a memory task consisting of immediate and delayed free recall of a list of positive, negative and neutral words. Memory performance was related to brain integrity in region of interest and whole-brain voxel-based morphometry analyses. In the brain-behavioral analyses, the left amygdala volume predicted the immediate recall of both positive and negative material, whereas at delay, left and right amygdala volumes were associated with performance with positive and negative words, respectively. Whole-brain analyses revealed additional associations between left angular gyrus integrity and the immediate recall of positive words as well as between the orbitofrontal cortex and the delayed recall of negative words. These results indicate that emotional memory impairments in AD may be underpinned by damage to regions implicated in emotional processing as well as frontoparietal regions, which may exert their influence via autobiographical memories and organizational strategies. PMID:24478669

Motivational orientation modulates the neural response to reward.

PubMed

Linke, Julia; Kirsch, Peter; King, Andrea V; Gass, Achim; Hennerici, Michael G; Bongers, André; Wessa, Michèle

2010-02-01

Motivational orientation defines the source of motivation for an individual to perform a particular action and can either originate from internal desires (e.g., interest) or external compensation (e.g., money). To this end, motivational orientation should influence the way positive or negative feedback is processed during learning situations and this might in turn have an impact on the learning process. In the present study, we thus investigated whether motivational orientation, i.e., extrinsic and intrinsic motivation modulates the neural response to reward and punishment as well as learning from reward and punishment in 33 healthy individuals. To assess neural responses to reward, punishment and learning of reward contingencies we employed a probabilistic reversal learning task during functional magnetic resonance imaging. Extrinsic and intrinsic motivation were assessed with a self-report questionnaire. Rewarding trials fostered activation in the medial orbitofrontal cortex and anterior cingulate gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment an increased neural response was observed in the medial and inferior prefrontal cortex, the superior parietal cortex and the insula. High extrinsic motivation was positively correlated to increased neural responses to reward in the ACC, amygdala and putamen, whereas a negative relationship between intrinsic motivation and brain activation in these brain regions was observed. These findings show that motivational orientation indeed modulates the responsiveness to reward delivery in major components of the human reward system and therefore extends previous results showing a significant influence of individual differences in reward-related personality traits on the neural processing of reward. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Functional neuroimaging studies of sexual arousal and orgasm in healthy men and women: a review and meta-analysis.

PubMed

Stoléru, Serge; Fonteille, Véronique; Cornélis, Christel; Joyal, Christian; Moulier, Virginie

2012-07-01

In the last fifteen years, functional neuroimaging techniques have been used to investigate the neuroanatomical correlates of sexual arousal in healthy human subjects. In most studies, subjects have been requested to watch visual sexual stimuli and control stimuli. Our review and meta-analysis found that in heterosexual men, sites of cortical activation consistently reported across studies are the lateral occipitotemporal, inferotemporal, parietal, orbitofrontal, medial prefrontal, insular, anterior cingulate, and frontal premotor cortices as well as, for subcortical regions, the amygdalas, claustrum, hypothalamus, caudate nucleus, thalami, cerebellum, and substantia nigra. Heterosexual and gay men show a similar pattern of activation. Visual sexual stimuli activate the amygdalas and thalami more in men than in women. Ejaculation is associated with decreased activation throughout the prefrontal cortex. We present a neurophenomenological model to understand how these multiple regional brain responses could account for the varied facets of the subjective experience of sexual arousal. Further research should shift from passive to active paradigms, focus on functional connectivity and use subliminal presentation of stimuli. Copyright © 2012 Elsevier Ltd. All rights reserved.

Olfactory function in psychotic disorders: Insights from neuroimaging studies

PubMed Central

Good, Kimberley P; Sullivan, Randii Lynn

2015-01-01

Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders. PMID:26110122

Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity.

PubMed

Holsen, L M; Savage, C R; Martin, L E; Bruce, A S; Lepping, R J; Ko, E; Brooks, W M; Butler, M G; Zarcone, J R; Goldstein, J M

2012-05-01

The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating. A total of 14 individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.

Importance of Reward and Prefrontal Circuitry in Hunger and Satiety: Prader-Willi Syndrome vs. Simple Obesity

PubMed Central

Holsen, Laura M.; Savage, Cary R.; Martin, Laura E.; Bruce, Amanda S.; Lepping, Rebecca J.; Ko, Eunice; Brooks, William M.; Butler, Merlin G.; Zarcone, Jennifer R.; Goldstein, Jill M.

2011-01-01

Background The majority of research on obesity has focused primarily on clinical features (eating behavior, adiposity measures), or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions which are associated with appetite-regulatory hormones are also involved in the development and maintenance of obesity. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic obesity. Simple (non-PWS) obesity (OB) represents an obesity control state. Objective This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (i.e., hypothalamus, amygdala) and prefrontal regions associated with cognitive control [i.e., dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC)] after eating. Design and Participants Fourteen individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls (HWC) viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC, and DLPFC. Results Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in hypothalamus and hippocampus, in response to food (vs. non-food) images pre-meal. Post-meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared to OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion In PWS compared with obesity per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple obesity. PMID:22024642

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.

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.

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

PubMed

Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David

2011-07-01

For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

Ability to Maintain Internal Arousal and Motivation Modulates Brain Responses to Emotions

PubMed Central

Sterpenich, Virginie; Schwartz, Sophie; Maquet, Pierre; Desseilles, Martin

2014-01-01

Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression. PMID:25438046

Ability to maintain internal arousal and motivation modulates brain responses to emotions.

PubMed

Sterpenich, Virginie; Schwartz, Sophie; Maquet, Pierre; Desseilles, Martin

2014-01-01

Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression.

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.

Molecular neuroeconomics of crime and punishment: implications for neurolaw.

PubMed

Takahashi, Taiki

2012-01-01

Criminal behaviors have been associated with risk, time and social preferences in economics (Becker 1968; Davis 1988), criminology (Chamlin & Cochran 1997), and neurolaw (Goodenough & Tucker 2010). This study proposes a molecular neuroeconomic framework for the investigation into crime and punishment. Neuroeconomic parameters (e.g., risk-attitude, probability weighting, time discounting in intertemporal choice, loss aversion, and social discounting) are predicted to be related to criminal behavior. Neurobiological and neuroendocrinological substrates such as serotonin, dopamine, norepinephrine, cortisol (a stress hormone), sex hormones (e.g., testosterone), and oxytocin in brain regions such as the orbitofrontal cortex, the amygdala, and the cingulate may be related to the neuroeconomic parameters governing criminal behaviors. The present framework may help us develop "neurolaw" based on molecular neuroeconomics of criminal and antisocial decision-making processes.

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.

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.

Neural substrates of decision-making.

PubMed

Broche-Pérez, Y; Herrera Jiménez, L F; Omar-Martínez, E

2016-06-01

Decision-making is the process of selecting a course of action from among 2 or more alternatives by considering the potential outcomes of selecting each option and estimating its consequences in the short, medium and long term. The prefrontal cortex (PFC) has traditionally been considered the key neural structure in decision-making process. However, new studies support the hypothesis that describes a complex neural network including both cortical and subcortical structures. The aim of this review is to summarise evidence on the anatomical structures underlying the decision-making process, considering new findings that support the existence of a complex neural network that gives rise to this complex neuropsychological process. Current evidence shows that the cortical structures involved in decision-making include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). This process is assisted by subcortical structures including the amygdala, thalamus, and cerebellum. Findings to date show that both cortical and subcortical brain regions contribute to the decision-making process. The neural basis of decision-making is a complex neural network of cortico-cortical and cortico-subcortical connections which includes subareas of the PFC, limbic structures, and the cerebellum. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

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

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.

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

Psychopathic traits are associated with cortical and subcortical volume alterations in healthy individuals.

PubMed

Vieira, Joana B; Ferreira-Santos, Fernando; Almeida, Pedro R; Barbosa, Fernando; Marques-Teixeira, João; Marsh, Abigail A

2015-12-01

Research suggests psychopathy is associated with structural brain alterations that may contribute to the affective and interpersonal deficits frequently observed in individuals with high psychopathic traits. However, the regional alterations related to different components of psychopathy are still unclear. We used voxel-based morphometry to characterize the structural correlates of psychopathy in a sample of 35 healthy adults assessed with the Triarchic Psychopathy Measure. Furthermore, we examined the regional grey matter alterations associated with the components described by the triarchic model. Our results showed that, after accounting for variation in total intracranial volume, age and IQ, overall psychopathy was negatively associated with grey matter volume in the left putamen and amygdala. Additional regression analysis with anatomical regions of interests revealed total triPM score was also associated with increased lateral orbitofrontal cortex (OFC) and caudate volume. Boldness was positively associated with volume in the right insula. Meanness was positively associated with lateral OFC and striatum volume, and negatively associated with amygdala volume. Finally, disinhibition was negatively associated with amygdala volume. Results highlight the contribution of both subcortical and cortical brain alterations for subclinical psychopathy and are discussed in light of prior research and theoretical accounts about the neurobiological bases of psychopathic traits. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

There are differences in cerebral activation between females in distinct menstrual phases during viewing of erotic stimuli: A fMRI study.

PubMed

Gizewski, Elke R; Krause, Eva; Karama, Sherif; Baars, Anneke; Senf, Wolfgang; Forsting, Michael

2006-09-01

There is evidence that men experience more sexual arousal than women but also that women in mid-luteal phase experience more sexual arousal than women outside this phase. Recently, a few functional brain imaging studies have tackled the issue of gender differences as pertaining to reactions to erotica. The question of whether or not gender differences in reactions to erotica are maintained with women in different phases has not yet been answered from a functional brain imaging perspective. In order to examine this issue, functional MRI was performed in 22 male and 22 female volunteers. Subjects viewed erotic film excerpts alternating with emotionally neutral excerpts in a standard block-design paradigm. Arousal to erotic stimuli was evaluated using standard rating scales after scanning. Two-sample t-test with uncorrected P < 0.001 values for a priori determined region of interests involved in processing of erotic stimuli and with corrected P < 0.05 revealed gender differences: Comparing women in mid-luteal phase and during their menses, superior activation was revealed for women in mid-luteal phase in the anterior cingulate, left insula, and orbitofrontal cortex. A superior activation for men was found in the left thalamus, the bilateral amygdala, the anterior cingulate, the bilateral orbitofrontal, bilateral parahippocampal, and insular regions, which were maintained at a corrected P in the amygdala, the insula, and thalamus. There were no areas of significant superior activation for women neither in mid-luteal phase nor during their menses. Our results indicate that there are differences between women in the two cycle times in cerebral activity during viewing of erotic stimuli. Furthermore, gender differences with women in mid-luteal phases are similar to those in females outside the mid-luteal phase.

Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex

PubMed Central

Hadj-Bouziane, Fadila; Liu, Ning; Bell, Andrew H.; Gothard, Katalin M.; Luh, Wen-Ming; Tootell, Roger B. H.; Murray, Elisabeth A.; Ungerleider, Leslie G.

2012-01-01

We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey’s amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the “valence effect.” We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions—neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)—were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies. PMID:23184972

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

Altered connections on the road to psychopathy.

PubMed

Craig, M C; Catani, M; Deeley, Q; Latham, R; Daly, E; Kanaan, R; Picchioni, M; McGuire, P K; Fahy, T; Murphy, D G M

2009-10-01

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

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.

Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder.

PubMed

Harrison, Ben J; Pujol, Jesus; Cardoner, Narcis; Deus, Joan; Alonso, Pino; López-Solà, Marina; Contreras-Rodríguez, Oren; Real, Eva; Segalàs, Cinto; Blanco-Hinojo, Laura; Menchon, José M; Soriano-Mas, Carles

2013-02-15

Functional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder's prominent clinical heterogeneity. To address these concerns, we investigated the influence of major OCD symptom dimensions on brain corticostriatal functional systems in a large sample of OCD patients (n = 74) and control participants (n = 74) examined with resting-state functional magnetic resonance imaging. We employed a valid method for mapping ventral and dorsal striatal functional connectivity, which supported both standard group comparisons and linear regression analyses with patients' scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Consistent with past findings, patients demonstrated a common connectivity alteration involving the ventral striatum and orbitofrontal cortex that predicted overall illness severity levels. This common alteration was independent of the effect of particular symptom dimensions. Instead, we observed distinct anatomical relationships between the severity of symptom dimensions and striatal functional connectivity. Aggression symptoms modulated connectivity between the ventral striatum, amygdala, and ventromedial frontal cortex, while sexual/religious symptoms had a specific influence on ventral striatal-insular connectivity. Hoarding modulated the strength of ventral and dorsal striatal connectivity with distributed frontal regions. Taken together, these results suggest that pathophysiological changes among orbitofrontal-striatal regions may be common to all forms of OCD. They suggest that a further examination of certain dimensional relationships will also be relevant for advancing current neurobiological models of the disorder. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Neurodevelopmental correlates of proneness to guilt and shame in adolescence and early adulthood.

PubMed

Whittle, Sarah; Liu, Kirra; Bastin, Coralie; Harrison, Ben J; Davey, Christopher G

2016-06-01

Investigating how brain development during adolescence and early adulthood underlies guilt- and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt- and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI). Sixty participants (age range: 15-25) completed sMRI and self-report measures of interpersonal guilt- and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC) thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC). Our findings highlight the complexities in understanding brain-behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neural connections foster social connections: a diffusion-weighted imaging study of social networks

PubMed Central

Hampton, William H.; Unger, Ashley; Von Der Heide, Rebecca J.

2016-01-01

Although we know the transition from childhood to adulthood is marked by important social and neural development, little is known about how social network size might affect neurocognitive development or vice versa. Neuroimaging research has identified several brain regions, such as the amygdala, as key to this affiliative behavior. However, white matter connectivity among these regions, and its behavioral correlates, remain unclear. Here we tested two hypotheses: that an amygdalocentric structural white matter network governs social affiliative behavior and that this network changes during adolescence and young adulthood. We measured social network size behaviorally, and white matter microstructure using probabilistic diffusion tensor imaging in a sample of neurologically normal adolescents and young adults. Our results suggest amygdala white matter microstructure is key to understanding individual differences in social network size, with connectivity to other social brain regions such as the orbitofrontal cortex and anterior temporal lobe predicting much variation. In addition, participant age correlated with both network size and white matter variation in this network. These findings suggest the transition to adulthood may constitute a critical period for the optimization of structural brain networks underlying affiliative behavior. PMID:26755769

Correlations of inflammatory gene pathways, corticolimbic functional activities, and aggression in pediatric bipolar disorder: a preliminary study.

PubMed

Barzman, Drew; Eliassen, Jim; McNamara, Robert; Abonia, Pablo; Mossman, Douglas; Durling, Michele; Adler, Caleb; DelBello, Melissa; Lin, Ping-I

2014-11-30

The mechanisms underlying aggression in adolescents with bipolar disorder have been poorly understood. The present study has investigated the associations among TNF gene expressions, functional brain activations under the frustrative non-reward task, and aggression in adolescents with bipolar disorder. Baseline gene expressions and aggressive tendencies were measured with the RNA-sequencing and Brief Rating of Aggression by Children and Adolescents (BRACHA), respectively. Our results show that activity levels of left subgenual anterior cingulate gyrus (ACG), right amygdala, left Brodmann area 10 (orbitofrontal cortex), and right thalamus were inversely correlated with BRACHA scores and were activated with frustrative non-reward during the affective Posner Task. In addition, 11 TNF related gene expressions were significantly correlated with activation of amygdala or ACG during the affective Posner Task. Three TNF gene expressions were inversely correlated with BRACHA score while one TNF gene (TNFAIP3) expression was positively correlated with BRACHA score. Therefore, TNF-related inflammatory cytokine genes may play a role in neural activity associated with frustrative non-reward and aggressive behaviors in pediatric bipolar disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neurophysiology of Reward-Guided Behavior: Correlates Related to Predictions, Value, Motivation, Errors, Attention, and Action.

PubMed

Bissonette, Gregory B; Roesch, Matthew R

2016-01-01

Many brain areas are activated by the possibility and receipt of reward. Are all of these brain areas reporting the same information about reward? Or are these signals related to other functions that accompany reward-guided learning and decision-making? Through carefully controlled behavioral studies, it has been shown that reward-related activity can represent reward expectations related to future outcomes, errors in those expectations, motivation, and signals related to goal- and habit-driven behaviors. These dissociations have been accomplished by manipulating the predictability of positively and negatively valued events. Here, we review single neuron recordings in behaving animals that have addressed this issue. We describe data showing that several brain areas, including orbitofrontal cortex, anterior cingulate, and basolateral amygdala signal reward prediction. In addition, anterior cingulate, basolateral amygdala, and dopamine neurons also signal errors in reward prediction, but in different ways. For these areas, we will describe how unexpected manipulations of positive and negative value can dissociate signed from unsigned reward prediction errors. All of these signals feed into striatum to modify signals that motivate behavior in ventral striatum and guide responding via associative encoding in dorsolateral striatum.

Neurophysiology of Reward-Guided Behavior: Correlates Related to Predictions, Value, Motivation, Errors, Attention, and Action

PubMed Central

Roesch, Matthew R.

2017-01-01

Many brain areas are activated by the possibility and receipt of reward. Are all of these brain areas reporting the same information about reward? Or are these signals related to other functions that accompany reward-guided learning and decision-making? Through carefully controlled behavioral studies, it has been shown that reward-related activity can represent reward expectations related to future outcomes, errors in those expectations, motivation, and signals related to goal- and habit-driven behaviors. These dissociations have been accomplished by manipulating the predictability of positively and negatively valued events. Here, we review single neuron recordings in behaving animals that have addressed this issue. We describe data showing that several brain areas, including orbitofrontal cortex, anterior cingulate, and basolateral amygdala signal reward prediction. In addition, anterior cingulate, basolateral amygdala, and dopamine neurons also signal errors in reward prediction, but in different ways. For these areas, we will describe how unexpected manipulations of positive and negative value can dissociate signed from unsigned reward prediction errors. All of these signals feed into striatum to modify signals that motivate behavior in ventral striatum and guide responding via associative encoding in dorsolateral striatum. PMID:26276036

Minocycline produced antidepressant-like effects on the learned helplessness rats with alterations in levels of monoamine in the amygdala and no changes in BDNF levels in the hippocampus at baseline.

PubMed

Arakawa, Shiho; Shirayama, Yukihiko; Fujita, Yuko; Ishima, Tamaki; Horio, Mao; Muneoka, Katsumasa; Iyo, Masaomi; Hashimoto, Kenji

2012-01-01

Previous studies have indicated that minocycline might function as an antidepressant drug. The aim of this study was to evaluate the antidepressant-like effects of minocycline, which is known to suppress activated microglia, using learned helplessness (LH) rats (an animal model of depression). Infusion of minocycline into the cerebral ventricle of LH rats induced antidepressant-like effects. However, infusion of minocycline into the cerebral ventricle of naïve rats did not produce locomotor activation in the open field tests, suggesting that the antidepressant-like effects of minocycline were not attributed to the enhanced locomotion. LH rats showed significantly higher serotonin turnover in the orbitofrontal cortex and lower levels of brain-derived neurotrophic factor (BDNF) in the hippocampus than control rats. However, these alterations in serotonin turnover and BDNF expression remained unchanged after treatment with minocycline. On the contrary, minocycline treatment of LH rats induced significant increases in the levels of dopamine and its metabolites in the amygdala when compared with untreated LH rats. Taken together, minocycline may be a therapeutic drug for the treatment of depression. Copyright © 2011 Elsevier Inc. All rights reserved.

Ageing diminishes the modulation of human brain responses to visual food cues by meal ingestion.

PubMed

Cheah, Y S; Lee, S; Ashoor, G; Nathan, Y; Reed, L J; Zelaya, F O; Brammer, M J; Amiel, S A

2014-09-01

Rates of obesity are greatest in middle age. Obesity is associated with altered activity of brain networks sensing food-related stimuli and internal signals of energy balance, which modulate eating behaviour. The impact of healthy mid-life ageing on these processes has not been characterised. We therefore aimed to investigate changes in brain responses to food cues, and the modulatory effect of meal ingestion on such evoked neural activity, from young adulthood to middle age. Twenty-four healthy, right-handed subjects, aged 19.5-52.6 years, were studied on separate days after an overnight fast, randomly receiving 50 ml water or 554 kcal mixed meal before functional brain magnetic resonance imaging while viewing visual food cues. Across the group, meal ingestion reduced food cue-evoked activity of amygdala, putamen, insula and thalamus, and increased activity in precuneus and bilateral parietal cortex. Corrected for body mass index, ageing was associated with decreasing food cue-evoked activation of right dorsolateral prefrontal cortex (DLPFC) and precuneus, and increasing activation of left ventrolateral prefrontal cortex (VLPFC), bilateral temporal lobe and posterior cingulate in the fasted state. Ageing was also positively associated with the difference in food cue-evoked activation between fed and fasted states in the right DLPFC, bilateral amygdala and striatum, and negatively associated with that of the left orbitofrontal cortex and VLPFC, superior frontal gyrus, left middle and temporal gyri, posterior cingulate and precuneus. There was an overall tendency towards decreasing modulatory effects of prior meal ingestion on food cue-evoked regional brain activity with increasing age. Healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food cue-evoked activity in brain regions that represent the salience of food and direct food-associated behaviour. Reduced satiety sensing may have a role in the greater risk of obesity in middle age.

Enhanced affective brain representations of chocolate in cravers vs. non-cravers.

PubMed

Rolls, Edmund T; McCabe, Ciara

2007-08-01

To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.

Amygdala functional disconnection with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood.

PubMed

Chen, Yu-Chen; Bo, Fan; Xia, Wenqing; Liu, Shenghua; Wang, Peng; Su, Wen; Xu, Jin-Jing; Xiong, Zhenyu; Yin, Xindao

2017-10-03

Chronic tinnitus is often accompanied with depressive symptom, which may arise from aberrant functional coupling between the amygdala and cerebral cortex. To explore this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to investigate the disrupted amygdala-cortical functional connectivity (FC) in chronic tinnitus patients with depressive mood. Chronic tinnitus patients with depressive mood (n=20), without depressive mood (n=20), and well-matched healthy controls (n=23) underwent resting-state fMRI scanning. Amygdala-cortical FC was characterized using a seed-based whole-brain correlation method. The bilateral amygdala FC was compared among the three groups. Compared to non-depressed patients, depressive tinnitus patients showed decreased amygdala FC with the prefrontal cortex and anterior cingulate cortex as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. Relative to healthy controls, depressive tinnitus patients revealed decreased amygdala FC with the superior and middle temporal gyrus, anterior and posterior cingulate cortex, and prefrontal cortex, as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. The current study identified for the first time abnormal resting-state amygdala-cortical FC with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood, which will provide novel insight into the underlying neuropathological mechanisms of tinnitus-induced depressive disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

The vomeronasal cortex - afferent and efferent projections of the posteromedial cortical nucleus of the amygdala in mice.

PubMed

Gutiérrez-Castellanos, Nicolás; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2014-01-01

Most mammals possess a vomeronasal system that detects predominantly chemical signals of biological relevance. Vomeronasal information is relayed to the accessory olfactory bulb (AOB), whose unique cortical target is the posteromedial cortical nucleus of the amygdala. This cortical structure should therefore be considered the primary vomeronasal cortex. In the present work, we describe the afferent and efferent connections of the posteromedial cortical nucleus of the amygdala in female mice, using anterograde (biotinylated dextranamines) and retrograde (Fluorogold) tracers, and zinc selenite as a tracer specific for zinc-enriched (putative glutamatergic) projections. The results show that the posteromedial cortical nucleus of the amygdala is strongly interconnected not only with the rest of the vomeronasal system (AOB and its target structures in the amygdala), but also with the olfactory system (piriform cortex, olfactory-recipient nuclei of the amygdala and entorhinal cortex). Therefore, the posteromedial cortical nucleus of the amygdala probably integrates olfactory and vomeronasal information. In addition, the posteromedial cortical nucleus of the amygdala shows moderate interconnections with the associative (basomedial) amygdala and with the ventral hippocampus, which may be involved in emotional and spatial learning (respectively) induced by chemical signals. Finally, the posteromedial cortical nucleus of the amygdala gives rise to zinc-enriched projections to the ventrolateral septum and the ventromedial striatum (including the medial islands of Calleja). This pattern of intracortical connections (with the olfactory cortex and hippocampus, mainly) and cortico-striatal excitatory projections (with the olfactory tubercle and septum) is consistent with its proposed nature as the primary vomeronasal cortex. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Neuroeconomics of attention-deficit/hyperactivity disorder: differential influences of medial, dorsal, and ventral prefrontal brain networks on suboptimal decision making?

PubMed

Sonuga-Barke, Edmund J S; Fairchild, Graeme

2012-07-15

Psychiatric neuroeconomics offers an alternative approach to understanding mental disorders by studying the way disorder-related neurobiological alterations constrain economic agency, as revealed through decisions about choices between future goods. In this article, we apply this perspective to understand suboptimal decision making in attention-deficit/hyperactivity disorder (ADHD) by integrating recent advances in the neuroscience of decision making and studies of the pathophysiology of ADHD. We identify three brain networks as candidates for further study and develop specific hypotheses about how these could be implicated in ADHD. First, we postulate that altered patterns of connectivity within a network linking medial prefrontal cortex and posterior cingulate cortex (i.e., the default mode network) disrupts ordering of utilities, prospection about desired future states, setting of future goals, and implementation of aims. Second, we hypothesize that deficits in dorsal frontostriatal networks, including the dorsolateral prefrontal cortex and dorsal striatum, produce executive dysfunction-mediated impairments in the ability to compare outcome options and make choices. Third, we propose that dopaminergic dysregulation in a ventral frontostriatal network encompassing the orbitofrontal cortex, ventral striatum, and amygdala disrupts processing of cues of future utility, evaluation of experienced outcomes (feedback), and learning of associations between cues and outcomes. Finally, we extend this perspective to consider three contemporary themes in ADHD research. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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…

Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect.

PubMed

Welborn, B Locke; Papademetris, Xenophon; Reis, Deidre L; Rajeevan, Nallakkandi; Bloise, Suzanne M; Gray, Jeremy R

2009-12-01

Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18-40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences.

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

Comparing Volume Loss in Neuroanatomical Regions of Emotion versus Regions of Cognition in Healthy Aging.

PubMed

Pressman, Peter S; Noniyeva, Yuliana; Bott, Nick; Dutt, Shubir; Sturm, Virginia; Miller, Bruce L; Kramer, Joel H

2016-01-01

Many emotional functions are relatively preserved in aging despite declines in several cognitive domains and physical health. High levels of happiness exist even among centenarians. To address the hypothesis of whether preservation of emotional function in healthy aging may relate to different rates of age-related volume loss across brain structures, we performed two volumetric analyses on structural magnetic resonance neuroimaging of a group of healthy aging research participants using Freesurfer version 5.1. Volumes selected as supporting cognition included bilateral midfrontal and lateral frontal gyri, lateral parietal and temporal cortex, and medial temporal lobes. Volumes supporting emotion included bilateral amygdala, rostral anterior cingulate, insula, orbitofrontal cortex, and nucleus accumbens. A cross-sectional analysis was performed using structural MRI scans from 258 subjects. We found no difference in proportional change between groups. A longitudinal mixed effects model was used to compare regional changes over time in a subset of 84 subjects. Again, there was no difference in proportional change over time. While our results suggest that aging does not collectively target cognitive brain regions more than emotional regions, subgroup analysis suggests relative preservation of the anterior cingulate cortex, with greater volume loss in the nucleus accumbens. Implications of these relative rates of age-related volume loss in healthy aging are discussed and merit further research.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

PubMed

Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

2018-01-29

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

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.

Differences in gray matter structure correlated to nationalism and patriotism

PubMed Central

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2016-01-01

Nationalism and patriotism both entail positive evaluations of one’s nation. However, the former inherently involves derogation of other nations, whereas the latter is independent of comparisons with other nations. We used voxel-based morphometry and psychological measures and determined nationalism and patriotism’s association with gray matter density (rGMD) and their cognitive nature in healthy individuals (433 men and 344 women; age, 20.7 ± 1.9 years) using whole-brain multiple regression analyses and post hoc analyses. We found higher nationalism associated with greater rGMD in (a) areas of the posterior cingulate cortex and greater rGMD in (b) the orbitofrontal cortex, and smaller rGMD in (c) the right amygdala area. Furthermore, we found higher patriotism associated with smaller rGMD in the (d) rostrolateral prefrontal cortex. Post hoc analyses revealed the mean rGMD of the cluster (a) associated with compassion, that of (b) associated with feeling of superiority, that of (c) associated with suicide ideation, and that of (d) associated with quality of life. These results indicate that individual nationalism may be mediated by neurocognitive mechanisms in social-related areas and limbic neural mechanisms, whereas patriotism may be mediated by neurocognitive mechanisms in areas related to well-being. PMID:27418362

Tyramide Signal Amplification Permits Immunohistochemical Analyses of Androgen Receptors in the Rat Prefrontal Cortex

PubMed Central

Low, Katelyn L.; Ma, Chunqi; Soma, Kiran K.

2017-01-01

Research on neural androgen receptors (ARs) has traditionally focused on brain regions that regulate reproductive and aggressive behaviors, such as the hypothalamus and amygdala. Although many cells in the prefrontal cortex (PFC) also express ARs, the number of ARs per cell appears to be much lower, and thus, AR immunostaining is often hard to detect and quantify in the PFC. Here, we demonstrate that biotin tyramide signal amplification (TSA) dramatically increases AR immunoreactivity in the rat brain, including critical regions of the PFC such as the medial PFC (mPFC) and orbitofrontal cortex (OFC). We show that TSA is useful for AR detection with both chromogenic and immunofluorescent immunohistochemistry. Double-labeling studies reveal that AR+ cells in the PFC and hippocampus are NeuN+ but not GFAP+ and thus primarily neuronal. Finally, in gonadally intact rats, more AR+ cells are present in the mPFC and OFC of males than of females. Future studies can use TSA to further examine AR immunoreactivity across ages, sexes, strains, and different procedures (e.g., fixation methods). In light of emerging evidence for the androgen regulation of executive function and working memory, these results may help understand the distribution and roles of ARs in the PFC. PMID:28438093

Amygdala and auditory cortex exhibit distinct sensitivity to relevant acoustic features of auditory emotions.

PubMed

Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

2016-12-01

Discriminating between auditory signals of different affective value is critical to successful social interaction. It is commonly held that acoustic decoding of such signals occurs in the auditory system, whereas affective decoding occurs in the amygdala. However, given that the amygdala receives direct subcortical projections that bypass the auditory cortex, it is possible that some acoustic decoding occurs in the amygdala as well, when the acoustic features are relevant for affective discrimination. We tested this hypothesis by combining functional neuroimaging with the neurophysiological phenomena of repetition suppression (RS) and repetition enhancement (RE) in human listeners. Our results show that both amygdala and auditory cortex responded differentially to physical voice features, suggesting that the amygdala and auditory cortex decode the affective quality of the voice not only by processing the emotional content from previously processed acoustic features, but also by processing the acoustic features themselves, when these are relevant to the identification of the voice's affective value. Specifically, we found that the auditory cortex is sensitive to spectral high-frequency voice cues when discriminating vocal anger from vocal fear and joy, whereas the amygdala is sensitive to vocal pitch when discriminating between negative vocal emotions (i.e., anger and fear). Vocal pitch is an instantaneously recognized voice feature, which is potentially transferred to the amygdala by direct subcortical projections. These results together provide evidence that, besides the auditory cortex, the amygdala too processes acoustic information, when this is relevant to the discrimination of auditory emotions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food.

PubMed

Goldstone, Anthony P; Prechtl, Christina G; Scholtz, Samantha; Miras, Alexander D; Chhina, Navpreet; Durighel, Giuliana; Deliran, Seyedeh S; Beckmann, Christian; Ghatei, Mohammad A; Ashby, Damien R; Waldman, Adam D; Gaylinn, Bruce D; Thorner, Michael O; Frost, Gary S; Bloom, Stephen R; Bell, Jimmy D

2014-06-01

Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food. In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data. Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task. Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss. © 2014 American Society for Nutrition.

COMT Val158Met polymorphism influences the susceptibility to framing in decision-making: OFC-amygdala functional connectivity as a mediator.

PubMed

Gao, Xiaoxue; Gong, Pingyuan; Liu, Jinting; Hu, Jie; Li, Yue; Yu, Hongbo; Gong, Xiaoliang; Xiang, Yang; Jiang, Changjun; Zhou, Xiaolin

2016-05-01

Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp 37:1880-1892, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk.

PubMed

Qiu, Anqi; Shen, Mojun; Buss, Claudia; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Wadhwa, Pathik D; Entringer, Sonja; Styner, Martin; Karnani, Neerja; Heim, Christine M; O'Donnell, Kieran J; Holbrook, Joanna D; Fortier, Marielle V; Meaney, Michael J

2017-05-01

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development. © The Author 2017. Published by Oxford University Press.

Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

PubMed

Kano, M; Coen, S J; Farmer, A D; Aziz, Q; Williams, S C R; Alsop, D C; Fukudo, S; O'Gorman, R L

2014-09-01

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

Three distinct fiber pathways of the bed nucleus of the stria terminalis to the amygdala and prefrontal cortex.

PubMed

Krüger, Oliver; Shiozawa, Thomas; Kreifelts, Benjamin; Scheffler, Klaus; Ethofer, Thomas

2015-05-01

The bed nucleus of the stria terminalis (BNST) is an important relay for multiple cortical and subcortical regions involved in processing anxiety as well as neuroendocrine and autonomic responses to stress, and it is thought to play a role in the dysregulation of these functions as well as in addictive behavior. While its architecture and connection profile have been thoroughly examined in animals, studies in humans have been limited to post-mortem histological descriptions of the BNST itself, not accounting for the distribution of its various connections. In the current study, we used diffusion-weighted magnetic resonance imaging (DW-MRI) to investigate the courses of fiber tracks connected to the BNST in humans. We restricted our seed region for probabilistic fiber tracking to the dorsal part of the BNST, as the ventral BNST is not distinguishable from the surrounding grey matter structures using magnetic resonance imaging. Our results show two distinct pathways of the BNST to the amygdala via the stria terminalis and the ansa peduncularis, as well as connections to the hypothalamus. Finally, we distinguished a route to the orbitofrontal cortex (OFC) running through the head of the caudate nucleus (CN) and the nucleus accumbens (NAcc). Pathways to brainstem regions were found to show a considerable inter-individual variability and thus no common pathway could be identified across participants. In summary, our findings reveal a complex network of brain structures involved in behavioral and neuroendocrine regulation, with the BNST in a central position. Copyright © 2015 Elsevier Ltd. All rights reserved.

Grey Matter Changes Associated with Heavy Cannabis Use: A Longitudinal sMRI Study.

PubMed

Koenders, Laura; Cousijn, Janna; Vingerhoets, Wilhelmina A M; van den Brink, Wim; Wiers, Reinout W; Meijer, Carin J; Machielsen, Marise W J; Veltman, Dick J; Goudriaan, Anneke E; de Haan, Lieuwe

2016-01-01

Cannabis is the most frequently used illicit drug worldwide. Cross-sectional neuroimaging studies suggest that chronic cannabis exposure and the development of cannabis use disorders may affect brain morphology. However, cross-sectional studies cannot make a conclusive distinction between cause and consequence and longitudinal neuroimaging studies are lacking. In this prospective study we investigate whether continued cannabis use and higher levels of cannabis exposure in young adults are associated with grey matter reductions. Heavy cannabis users (N = 20, age baseline M = 20.5, SD = 2.1) and non-cannabis using healthy controls (N = 22, age baseline M = 21.6, SD = 2.45) underwent a comprehensive psychological assessment and a T1- structural MRI scan at baseline and 3 years follow-up. Grey matter volumes (orbitofrontal cortex, anterior cingulate cortex, insula, striatum, thalamus, amygdala, hippocampus and cerebellum) were estimated using the software package SPM (VBM-8 module). Continued cannabis use did not have an effect on GM volume change at follow-up. Cross-sectional analyses at baseline and follow-up revealed consistent negative correlations between cannabis related problems and cannabis use (in grams) and regional GM volume of the left hippocampus, amygdala and superior temporal gyrus. These results suggests that small GM volumes in the medial temporal lobe are a risk factor for heavy cannabis use or that the effect of cannabis on GM reductions is limited to adolescence with no further damage of continued use after early adulthood. Long-term prospective studies starting in early adolescence are needed to reach final conclusions.

Grey Matter Changes Associated with Heavy Cannabis Use: A Longitudinal sMRI Study

PubMed Central

Cousijn, Janna; Vingerhoets, Wilhelmina A. M.; van den Brink, Wim; Wiers, Reinout W.; Meijer, Carin J.; Machielsen, Marise W. J.; Veltman, Dick J.; Goudriaan, Anneke E.; de Haan, Lieuwe

2016-01-01

Cannabis is the most frequently used illicit drug worldwide. Cross-sectional neuroimaging studies suggest that chronic cannabis exposure and the development of cannabis use disorders may affect brain morphology. However, cross-sectional studies cannot make a conclusive distinction between cause and consequence and longitudinal neuroimaging studies are lacking. In this prospective study we investigate whether continued cannabis use and higher levels of cannabis exposure in young adults are associated with grey matter reductions. Heavy cannabis users (N = 20, age baseline M = 20.5, SD = 2.1) and non-cannabis using healthy controls (N = 22, age baseline M = 21.6, SD = 2.45) underwent a comprehensive psychological assessment and a T1- structural MRI scan at baseline and 3 years follow-up. Grey matter volumes (orbitofrontal cortex, anterior cingulate cortex, insula, striatum, thalamus, amygdala, hippocampus and cerebellum) were estimated using the software package SPM (VBM-8 module). Continued cannabis use did not have an effect on GM volume change at follow-up. Cross-sectional analyses at baseline and follow-up revealed consistent negative correlations between cannabis related problems and cannabis use (in grams) and regional GM volume of the left hippocampus, amygdala and superior temporal gyrus. These results suggests that small GM volumes in the medial temporal lobe are a risk factor for heavy cannabis use or that the effect of cannabis on GM reductions is limited to adolescence with no further damage of continued use after early adulthood. Long-term prospective studies starting in early adolescence are needed to reach final conclusions. PMID:27224247

Altered neural processing of emotional faces in remitted Cushing's disease.

PubMed

Bas-Hoogendam, Janna Marie; Andela, Cornelie D; van der Werff, Steven J A; Pannekoek, J Nienke; van Steenbergen, Henk; Meijer, Onno C; van Buchem, Mark A; Rombouts, Serge A R B; van der Mast, Roos C; Biermasz, Nienke R; van der Wee, Nic J A; Pereira, Alberto M

2015-09-01

Patients with long-term remission of Cushing's disease (CD) demonstrate residual psychological complaints. At present, it is not known how previous exposure to hypercortisolism affects psychological functioning in the long-term. Earlier magnetic resonance imaging (MRI) studies demonstrated abnormalities of brain structure and resting-state connectivity in patients with long-term remission of CD, but no data are available on functional alterations in the brain during the performance of emotional or cognitive tasks in these patients. We performed a cross-sectional functional MRI study, investigating brain activation during emotion processing in patients with long-term remission of CD. Processing of emotional faces versus a non-emotional control condition was examined in 21 patients and 21 matched healthy controls. Analyses focused on activation and connectivity of two a priori determined regions of interest: the amygdala and the medial prefrontal-orbitofrontal cortex (mPFC-OFC). We also assessed psychological functioning, cognitive failure, and clinical disease severity. Patients showed less mPFC activation during processing of emotional faces compared to controls, whereas no differences were found in amygdala activation. An exploratory psychophysiological interaction analysis demonstrated decreased functional coupling between the ventromedial PFC and posterior cingulate cortex (a region structurally connected to the PFC) in CD-patients. The present study is the first to show alterations in brain function and task-related functional coupling in patients with long-term remission of CD relative to matched healthy controls. These alterations may, together with abnormalities in brain structure, be related to the persisting psychological morbidity in patients with CD after long-term remission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multimodal Neuroimaging of Frontolimbic Structure and Function Associated With Suicide Attempts in Adolescents and Young Adults With Bipolar Disorder.

PubMed

Johnston, Jennifer A Y; Wang, Fei; Liu, Jie; Blond, Benjamin N; Wallace, Amanda; Liu, Jiacheng; Spencer, Linda; Cox Lippard, Elizabeth T; Purves, Kirstin L; Landeros-Weisenberger, Angeli; Hermes, Eric; Pittman, Brian; Zhang, Sheng; King, Robert; Martin, Andrés; Oquendo, Maria A; Blumberg, Hilary P

2017-07-01

Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems. The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality. Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.

Multimodal Neuroimaging of Fronto-limbic Structure and Function Associated with Suicide Attempts in Adolescents and Young Adults with Bipolar Disorder

PubMed Central

Johnston, Jennifer A. Y.; Wang, Fei; Liu, Jie; Blond, Benjamin N.; Wallace, Amanda; Liu, Jiacheng; Spencer, Linda; Cox Lippard, Elizabeth T.; Purves, Kirstin L.; Landeros-Weisenberger, Angeli; Hermes, Eric; Pittman, Brian; Zhang, Sheng; King, Robert; Martin, Andrés; Oquendo, Maria A.; Blumberg, Hilary P.

2018-01-01

Objective Bipolar disorder is associated with high risk for suicide behavior that often develops in adolescence/young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents/young adults with bipolar disorder with and without history of suicide attempts combines structural, diffusion tensor and functional magnetic resonance imaging methods to investigate implicated abnormalities in structural and functional connectivity within fronto-limbic systems. Method Participants with bipolar disorder included 26 with a prior suicide attempt and 42 without attempts. Regional gray matter volume, white matter integrity and functional connectivity during processing of emotional stimuli were compared between groups and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Results Compared to the non-attempter group, the attempter group showed reductions in gray matter volume in orbitofrontal cortex, hippocampus and cerebellum; white matter integrity in uncinate fasciculus, ventral frontal and right cerebellum regions; and amygdala functional connectivity to left ventral and right rostral prefrontal cortex (p<0.05, corrected). In exploratory analyses, among attempters, right rostral prefrontal connectivity was negatively correlated with suicidal ideation (p<0.05), and left ventral prefrontal connectivity was negatively correlated with attempt lethality (p<0.05). Conclusions Adolescent/young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral fronto-limbic neural system subserving emotion regulation. Among suicide attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicide ideation and attempt lethality. PMID:28135845

Complexity and Competition in Appetitive and Aversive Neural Circuits

PubMed Central

Barberini, Crista L.; Morrison, Sara E.; Saez, Alex; Lau, Brian; Salzman, C. Daniel

2012-01-01

Decision-making often involves using sensory cues to predict possible rewarding or punishing reinforcement outcomes before selecting a course of action. Recent work has revealed complexity in how the brain learns to predict rewards and punishments. Analysis of neural signaling during and after learning in the amygdala and orbitofrontal cortex, two brain areas that process appetitive and aversive stimuli, reveals a dynamic relationship between appetitive and aversive circuits. Specifically, the relationship between signaling in appetitive and aversive circuits in these areas shifts as a function of learning. Furthermore, although appetitive and aversive circuits may often drive opposite behaviors – approaching or avoiding reinforcement depending upon its valence – these circuits can also drive similar behaviors, such as enhanced arousal or attention; these processes also may influence choice behavior. These data highlight the formidable challenges ahead in dissecting how appetitive and aversive neural circuits interact to produce a complex and nuanced range of behaviors. PMID:23189037

Reward-Guided Learning with and without Causal Attribution

PubMed Central

Jocham, Gerhard; Brodersen, Kay H.; Constantinescu, Alexandra O.; Kahn, Martin C.; Ianni, Angela M.; Walton, Mark E.; Rushworth, Matthew F.S.; Behrens, Timothy E.J.

2016-01-01

Summary When an organism receives a reward, it is crucial to know which of many candidate actions caused this reward. However, recent work suggests that learning is possible even when this most fundamental assumption is not met. We used novel reward-guided learning paradigms in two fMRI studies to show that humans deploy separable learning mechanisms that operate in parallel. While behavior was dominated by precise contingent learning, it also revealed hallmarks of noncontingent learning strategies. These learning mechanisms were separable behaviorally and neurally. Lateral orbitofrontal cortex supported contingent learning and reflected contingencies between outcomes and their causal choices. Amygdala responses around reward times related to statistical patterns of learning. Time-based heuristic mechanisms were related to activity in sensorimotor corticostriatal circuitry. Our data point to the existence of several learning mechanisms in the human brain, of which only one relies on applying known rules about the causal structure of the task. PMID:26971947

Neural evidence for Reference-dependence in real-market-transactions.

PubMed

Weber, Bernd; Aholt, Andreas; Neuhaus, Carolin; Trautner, Peter; Elger, Christian E; Teichert, Thorsten

2007-03-01

Human decision making has become one of the major research-foci in economics, marketing and in neuroscience. This study integrates perspectives from these disciplines by examining neurophysiological correlates to Reference-dependence of utility evaluations in real market contexts both before and after choice. First, by comparing buying and selling decisions, we observe an activation of the amygdala only in the latter. We interpret this as loss aversion with respect to prior possessions. This finding contributes to the settling of an ongoing fundamental dispute in economic theory by indicating the absence of loss aversion for money in routine transactions. Second, ex post satisfaction statements are accompanied by an activation of the reward processing orbitofrontal cortex, if the evaluation context is framed by a high external reference price instead of a lower internal reference price. This indicates a nonrational Reference-dependence--despite the neoclassical view of a rational Homo Economicus--of satisfaction measures and challenges a central marketing variable.

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

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.

Altered intrinsic functional brain architecture in female patients with bulimia nervosa

PubMed Central

Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun’Ai; Correll, Christoph U.; Mitchell, Philip B.; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

2017-01-01

Background Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. Methods We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. Results We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. Limitations We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Conclusion Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa. PMID:28949286

Altered intrinsic functional brain architecture in female patients with bulimia nervosa.

PubMed

Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun'Ai; Correll, Christoph U; Mitchell, Philip B; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

2017-11-01

Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa.

Risky decisions and their consequences: neural processing by boys with Antisocial Substance Disorder.

PubMed

Crowley, Thomas J; Dalwani, Manish S; Mikulich-Gilbertson, Susan K; Du, Yiping P; Lejuez, Carl W; Raymond, Kristen M; Banich, Marie T

2010-09-22

Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys. We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere. Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.

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

A functional connectivity comparison between attention deficit hyperactivity disorder and bipolar disorder in medication-naïve adolescents with mood fluctuation and attention problems.

PubMed

Son, Young Don; Han, Doug Hyun; Kim, Sun Mi; Min, Kyung Joon; Renshaw, Perry F

2017-05-30

In order to compare patterns of connectivity between affective and attention networks in adolescents with bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD), we investigated differences in resting state functional connectivity (RSFC) between these populations. Study participants were medication-naïve adolescents (aged 13-18 years) with BD (N=22) or ADHD (N=25) and age- and sex-matched healthy adolescents (healthy controls [HC]) (N=22). Forty-seven adolescents with mood fluctuation and attention problems showed increased functional correlation (FC) between two pairs of regions within the affective network (AFN), compared to 22 HC: the left orbitofrontal cortex (OFC) to the left thalamus and the left OFC to the right thalamus. In post-hoc testing, adolescents with BD showed increased FC between two pairs of regions compared to ADHD: the right amygdala to the left temporoparietal junction (TPJ) and the right amygdala to the right TPJ. Adolescents with BD showed increased FC within the attention network (ATN) as well as increased FC between the ATN and the AFN, while those with ADHD showed decreased FC within the ATN. The current suggests that these features could be used as biomarkers for differentiating BD from ADHD in adolescents. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Decreased functional connectivity in schizophrenia: The relationship between social functioning, social cognition and graph theoretical network measures.

PubMed

Erdeniz, Burak; Serin, Emin; İbadi, Yelda; Taş, Cumhur

2017-12-30

Schizophrenia is a complex disorder in which abnormalities in brain connectivity and social functioning play a central role. The aim of this study is to explore small-world network properties, and understand their relationship with social functioning and social cognition in the context of schizophrenia, by testing functional connectivity differences in network properties and its relation to clinical behavioral measures. Resting-state fMRI time series data were acquired from 23 patients diagnosed with schizophrenia and 23 healthy volunteers. The results revealed that patients with schizophrenia show significantly decreased connectivity between a range of brain regions, particularly involving connections among the right orbitofrontal cortex, bilateral putamen and left amygdala. Furthermore, topological properties of functional brain networks in patients with schizophrenia were characterized by reduced path length compared to healthy controls; however, no significant difference was found for clustering coefficient, local efficiency or global efficiency. Additionally, we found that nodal efficiency of the amygdala and the putamen were significantly correlated with the independence-performance subscale of social functioning scale (SFC), and Reading the Mind in the Eyes test; however, the correlations do not survive correction for multiple comparison. The current results help to clarify the relationship between social functioning deficits and topological brain measures in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Olfactory-visual integration facilitates perception of subthreshold negative emotion.

PubMed

Novak, Lucas R; Gitelman, Darren R; Schuyler, Brianna; Li, Wen

2015-10-01

A fast growing literature of multisensory emotion integration notwithstanding, the chemical senses, intimately associated with emotion, have been largely overlooked. Moreover, an ecologically highly relevant principle of "inverse effectiveness", rendering maximal integration efficacy with impoverished sensory input, remains to be assessed in emotion integration. Presenting minute, subthreshold negative (vs. neutral) cues in faces and odors, we demonstrated olfactory-visual emotion integration in improved emotion detection (especially among individuals with weaker perception of unimodal negative cues) and response enhancement in the amygdala. Moreover, while perceptual gain for visual negative emotion involved the posterior superior temporal sulcus/pSTS, perceptual gain for olfactory negative emotion engaged both the associative olfactory (orbitofrontal) cortex and amygdala. Dynamic causal modeling (DCM) analysis of fMRI timeseries further revealed connectivity strengthening among these areas during crossmodal emotion integration. That multisensory (but not low-level unisensory) areas exhibited both enhanced response and region-to-region coupling favors a top-down (vs. bottom-up) account for olfactory-visual emotion integration. Current findings thus confirm the involvement of multisensory convergence areas, while highlighting unique characteristics of olfaction-related integration. Furthermore, successful crossmodal binding of subthreshold aversive cues not only supports the principle of "inverse effectiveness" in emotion integration but also accentuates the automatic, unconscious quality of crossmodal emotion synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of contingency awareness on neural, electrodermal and evaluative responses during fear conditioning

PubMed Central

Merz, Christian J.; Klucken, Tim; Schweckendiek, Jan; Vaitl, Dieter; Wolf, Oliver T.; Stark, Rudolf

2011-01-01

In an fMRI study, effects of contingency awareness on conditioned responses were assessed in three groups comprising 118 subjects. A differential fear-conditioning paradigm with visual conditioned stimuli, an electrical unconditioned stimulus and two distractors was applied. The instructed aware group was informed about the contingencies, whereas the distractors prevented contingency detection in the unaware group. The third group (learned aware) was not informed about the contingencies, but learned them despite the distractors. Main effects of contingency awareness on conditioned responses emerged in several brain structures. Post hoc tests revealed differential dorsal anterior cingulate, insula and ventral striatum responses in aware conditioning only, whereas the amygdala was activated independent of contingency awareness. Differential responses of the hippocampus were specifically observed in learned aware subjects, indicating a role in the development of contingency awareness. The orbitofrontal cortex showed varying response patterns: lateral structures showed higher responses in instructed aware than unaware subjects, the opposite was true for medial parts. Conditioned subjective and electrodermal responses emerged only in the two aware groups. These results confirm the independence of conditioned amygdala responses from contingency awareness and indicate specific neural circuits for different aspects of fear acquisition in unaware, learned aware and instructed aware subjects. PMID:20693389

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

The neural signature of satiation is associated with ghrelin response and triglyceride metabolism

PubMed Central

Sun, Xue; Veldhuizen, Maria G; Wray, Amanda E; de Araujo, Ivan E; Sherwin, Robert S; Sinha, Rajita; Small, Dana M

2014-01-01

Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used fMRI to measure brain response to a palatable food (milkshake) when n=32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty acids. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination. PMID:24732416

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

Neural correlates of novelty and appropriateness processing in externally induced constraint relaxation.

PubMed

Huang, Furong; Tang, Shuang; Sun, Pei; Luo, Jing

2018-05-15

Novelty and appropriateness are considered the two fundamental features of creative thinking, including insight problem solving, which can be performed through chunk decomposition and constraint relaxation. Based on a previous study that separated the neural bases of novelty and appropriateness in chunk decomposition, in this study, we used event-related functional magnetic resonance imaging (fMRI) to further dissociate these mechanisms in constraint relaxation. Participants were guided to mentally represent the method of problem solving according to the externally provided solutions that were elaborately prepared in advance and systematically varied in their novelty and appropriateness for the given problem situation. The results showed that novelty processing was completed by the temporoparietal junction (TPJ) and regions in the executive system (dorsolateral prefrontal cortex [DLPFC]), whereas appropriateness processing was completed by the TPJ and regions in the episodic memory (hippocampus), emotion (amygdala), and reward systems (orbitofrontal cortex [OFC]). These results likely indicate that appropriateness processing can result in a more memorable and richer experience than novelty processing in constraint relaxation. The shared and distinct neural mechanisms of the features of novelty and appropriateness in constraint relaxation are discussed, enriching the representation of the change theory of insight. Copyright © 2018 Elsevier Inc. 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.

Dissociable neural modulation underlying lasting first impressions, changing your mind for the better, and changing it for the worse.

PubMed

Bhanji, Jamil P; Beer, Jennifer S

2013-05-29

Unattractive job candidates face a disadvantage when interviewing for a job. Employers' evaluations are colored by the candidate's physical attractiveness even when they take job interview performance into account. This example illustrates unexplored questions about the neural basis of social evaluation in humans. What neural regions support the lasting effects of initial impressions (even after getting to know someone)? How does the brain process information that changes our minds about someone? Job candidates' competence was evaluated from photographs and again after seeing snippets of job interviews. Left lateral orbitofrontal cortex modulation serves as a warning signal for initial reactions that ultimately undermine evaluations even when additional information is taken into account. The neural basis of changing one's mind about a candidate is not a simple matter of computing the amount of competence-affirming information in their job interview. Instead, seeing a candidate for the better is somewhat distinguishable at the neural level from seeing a candidate for the worse. Whereas amygdala modulation marks the extremity of evaluation change, favorable impression change additionally draws on parametric modulation of lateral prefrontal cortex and unfavorable impression change additionally draws on parametric modulation of medial prefrontal cortex, temporal cortex, and striatum. Investigating social evaluation as a dynamic process (rather than a one-time impression) paints a new picture of its neural basis and highlights the partially dissociable processes that contribute to changing your mind about someone for the better or the worse.

Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

PubMed Central

Crunelle, Cleo L; Veltman, Dick J; Booij, Jan; Emmerik – van Oortmerssen, Katelijne; den Brink, Wim

2012-01-01

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence, and excessive caffeine use, comparing stimulant abusers (SAs) to nondrug using healthy controls (HCs). Despite some inconsistencies, most studies indicated altered brain activation in prefrontal cortex (PFC) and insula in response to reward and punishment, and higher limbic and anterior cingulate cortex (ACC)/PFC activation during craving and attentional bias paradigms in SAs compared with HCs. Impulsivity in SAs was associated with lower ACC and presupplementary motor area activity compared with HCs, and related to both ventral (amygdala, ventrolateral PFC, insula) and dorsal (dorsolateral PFC, dorsal ACC, posterior parietal cortex) systems. Decision making in SAs was associated with low dorsolateral PFC activity and high orbitofrontal activity. Finally, executive function in SAs was associated with lower activation in frontotemporal regions and higher activation in premotor cortex compared with HCs. It is concluded that the lower activations compared with HCs are likely to reflect the neural substrate of impaired neurocognitive functions, whereas higher activations in SAs compared with HCs are likely to reflect compensatory cognitive control mechanisms to keep behavioral task performance to a similar level as in HCs. However, before final conclusions can be drawn, additional research is needed using neuroimaging in SAs and HCs using larger and more homogeneous samples as well as more comparable task paradigms, study designs, and statistical analyses. PMID:22950052

Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways.

PubMed

Ferrari, P F; Gerbella, M; Coudé, G; Rozzi, S

2017-09-01

The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing. Copyright © 2017. Published by Elsevier Ltd.

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.

Selective attention modulates high-frequency activity in the face-processing network.

PubMed

Müsch, Kathrin; Hamamé, Carlos M; Perrone-Bertolotti, Marcela; Minotti, Lorella; Kahane, Philippe; Engel, Andreas K; Lachaux, Jean-Philippe; Schneider, Till R

2014-11-01

Face processing depends on the orchestrated activity of a large-scale neuronal network. Its activity can be modulated by attention as a function of task demands. However, it remains largely unknown whether voluntary, endogenous attention and reflexive, exogenous attention to facial expressions equally affect all regions of the face-processing network, and whether such effects primarily modify the strength of the neuronal response, the latency, the duration, or the spectral characteristics. We exploited the good temporal and spatial resolution of intracranial electroencephalography (iEEG) and recorded from depth electrodes to uncover the fast dynamics of emotional face processing. We investigated frequency-specific responses and event-related potentials (ERP) in the ventral occipito-temporal cortex (VOTC), ventral temporal cortex (VTC), anterior insula, orbitofrontal cortex (OFC), and amygdala when facial expressions were task-relevant or task-irrelevant. All investigated regions of interest (ROI) were clearly modulated by task demands and exhibited stronger changes in stimulus-induced gamma band activity (50-150 Hz) when facial expressions were task-relevant. Observed latencies demonstrate that the activation is temporally coordinated across the network, rather than serially proceeding along a processing hierarchy. Early and sustained responses to task-relevant faces in VOTC and VTC corroborate their role for the core system of face processing, but they also occurred in the anterior insula. Strong attentional modulation in the OFC and amygdala (300 msec) suggests that the extended system of the face-processing network is only recruited if the task demands active face processing. Contrary to our expectation, we rarely observed differences between fearful and neutral faces. Our results demonstrate that activity in the face-processing network is susceptible to the deployment of selective attention. Moreover, we show that endogenous attention operates along the whole face-processing network, and that these effects are reflected in frequency-specific changes in the gamma band. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

PubMed Central

Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

2014-01-01

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

Functional Connectivity of the Amygdala Is Disrupted in Preschool-Aged Children With Autism Spectrum Disorder.

PubMed

Shen, Mark D; Li, Deana D; Keown, Christopher L; Lee, Aaron; Johnson, Ryan T; Angkustsiri, Kathleen; Rogers, Sally J; Müller, Ralph-Axel; Amaral, David G; Nordahl, Christine Wu

2016-09-01

The objective of this study was to determine whether functional connectivity of the amygdala is altered in preschool-age children with autism spectrum disorder (ASD) and to assess the clinical relevance of observed alterations in amygdala connectivity. A resting-state functional connectivity magnetic resonance imaging study of the amygdala (and a parallel study of primary visual cortex) was conducted in 72 boys (mean age 3.5 years; n = 43 with ASD; n = 29 age-matched controls). The ASD group showed significantly weaker connectivity between the amygdala and several brain regions involved in social communication and repetitive behaviors, including bilateral medial prefrontal cortex, temporal lobes, and striatum (p < .05, corrected). Weaker connectivity between the amygdala and frontal and temporal lobes was significantly correlated with increased autism severity in the ASD group (p < .05). In a parallel analysis examining the functional connectivity of primary visual cortex, the ASD group showed significantly weaker connectivity between visual cortex and sensorimotor regions (p < .05, corrected). Weaker connectivity between visual cortex and sensorimotor regions was not correlated with core autism symptoms, but instead was correlated with increased sensory hypersensitivity in the visual/auditory domain (p < .05). These findings indicate that preschool-age children with ASD have disrupted functional connectivity between the amygdala and regions of the brain important for social communication and language, which might be clinically relevant because weaker connectivity was associated with increased autism severity. Moreover, although amygdala connectivity was associated with behavioral domains that are diagnostic of ASD, altered connectivity of primary visual cortex was related to sensory hypersensitivity. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

PubMed

Vuilleumier, Patrik; Richardson, Mark P; Armony, Jorge L; Driver, Jon; Dolan, Raymond J

2004-11-01

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment.

PubMed

Sanguedo, Frederico Velasco; Dias, Caio Vitor Bueno; Dias, Flavia Regina Cruz; Samuels, Richard Ian; Carey, Robert J; Carrera, Marinete Pinheiro

2016-03-01

Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. Assess the role of the amygdala in emotional responses. Experimental manipulations were performed in which environmental familiarity was the variable. To provide the maximal degree of familiarity, ERK was measured after removal from the home cage and re-placement back into the same cage. To maximize exposure to an unfamiliar environment, ERK was measured following placement into a novel open field. To assess whether familiarity was the critical variable in the ERK response to the novel open field, ERK was also measured after either four or eight placements into the same environment. ERK quantification was carried out in the amygdala, frontal cortex, and the nucleus accumbens. After home cage re-placement, ERK activation was found in the frontal cortex and nucleus accumbens but was absent in the amygdala. Following placement in a novel environment, ERK activation was more prominent in the amygdala than the frontal cortex or nucleus accumbens. In contrast, with habituation to the novel environment, ERK phosphors declined markedly in the amygdala but increased in the frontal cortex and nucleus accumbens to the level observed following home cage re-placement. The differential responsiveness of the amygdala versus the frontal cortex and the nucleus accumbens to a novel versus a habituated environment is consistent with a reciprocal interaction between these neural systems and points to their important role in the mediation of behavioral activation to novelty and behavioral inactivation with habituation.

Examining the effect of psychopathic traits on gray matter volume in a community substance abuse sample.

PubMed

Cope, Lora M; Shane, Matthew S; Segall, Judith M; Nyalakanti, Prashanth K; Stevens, Michael C; Pearlson, Godfrey D; Calhoun, Vince D; Kiehl, Kent A

2012-11-30

Psychopathy is believed to be associated with brain abnormalities in both paralimbic (i.e., orbitofrontal cortex, insula, temporal pole, parahippocampal gyrus, posterior cingulate) and limbic (i.e., amygdala, hippocampus, anterior cingulate) regions. Recent structural imaging studies in both community and prison samples are beginning to support this view. Sixty-six participants, recruited from community corrections centers, were administered the Hare psychopathy checklist-revised (PCL-R), and underwent magnetic resonance imaging (MRI). Voxel-based morphometry was used to test the hypothesis that psychopathic traits would be associated with gray matter reductions in limbic and paralimbic regions. Effects of lifetime drug and alcohol use on gray matter volume were covaried. Psychopathic traits were negatively associated with gray matter volumes in right insula and right hippocampus. Additionally, psychopathic traits were positively associated with gray matter volumes in bilateral orbital frontal cortex and right anterior cingulate. Exploratory regression analyses indicated that gray matter volumes within right hippocampus and left orbital frontal cortex combined to explain 21.8% of the variance in psychopathy scores. These results support the notion that psychopathic traits are associated with abnormal limbic and paralimbic gray matter volume. Furthermore, gray matter increases in areas shown to be functionally impaired suggest that the structure-function relationship may be more nuanced than previously thought. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Emotion, Decision-Making and Substance Dependence: A Somatic-Marker Model of Addiction

PubMed Central

Verdejo-García, A; Pérez-García, M; Bechara, A

2006-01-01

Similar to patients with orbitofrontal cortex lesions, substance dependent individuals (SDI) show signs of impairments in decision-making, characterised by a tendency to choose the immediate reward at the expense of severe negative future consequences. The somatic-marker hypothesis proposes that decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between abnormalities in experiencing emotions in SDI, and their severe impairments in decision-making in real-life. Growing evidence from neuroscientific studies suggests that core aspects of substance addiction may be explained in terms of abnormal emotional guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in SDI. Combined neuropsychological and physiological assessment has demonstrated that the poorer decision-making of SDI is associated with altered reactions to reward and punishing events. Imaging studies have shown that impaired decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, including the ventromedial cortex, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker model of addiction. PMID:18615136

Men versus women on sexual brain function: prominent differences during tactile genital stimulation, but not during orgasm.

PubMed

Georgiadis, Janniko R; Reinders, A A T Simone; Paans, Anne M J; Renken, Remco; Kortekaas, Rudie

2009-10-01

Biological differences in male and female sexuality are obvious in the behavioral domain, but the central mechanisms that might explain these behavioral gender differences remain unclear. In this study, we merged two earlier positron emission tomography data sets to enable systematic comparison of the brain responses in heterosexual men and women during sexual tactile genital (penile and clitoral) stimulation and during orgasm. Gender commonalities were most evident during orgasm, a phase which demonstrated activations in the anterior lobe of the cerebellar vermis and deep cerebellar nuclei, and deactivations in the left ventromedial and orbitofrontal cortex in both men and women. During tactile genital stimulation, deactivations in the right amygdala and left fusiform gyrus were found for both genders. Marked gender differences were seen during this phase: left fronto-parietal areas (motor cortices, somatosensory area 2 and posterior parietal cortex) were activated more in women, whereas in men, the right claustrum and ventral occipitotemporal cortex showed larger activation. The only prominent gender difference during orgasm was male-biased activation of the periaqueductal gray matter. From these results, we conclude that during the sexual act, differential brain responses across genders are principally related to the stimulatory (plateau) phase and not to the orgasmic phase itself. These results add to a better understanding of the neural underpinnings of human sexuality, which might benefit treatment of psychosexual disorders.

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.

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

Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia

PubMed Central

Satterthwaite, Theodore D.; Wolf, Daniel H.; Loughead, James; Ruparel, Kosha; Valdez, Jeffrey N.; Siegel, Steven J.; Kohler, Christian G.; Gur, Raquel E.; Gur, Ruben C.

2014-01-01

Objective Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. Here we used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Methods fMRI (3T) BOLD response was examined in 21 controls and 16 patients during a two-choice recognition task using images of human faces. Each target face had previously been displayed with a threatening or non-threatening affect, but here were displayed with neutral affect. Responses to successful recognition and for the effect of previously threatening vs. non-threatening affect were evaluated, and correlations with total BPRS examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Results Patients performed the task more slowly than controls. Controls recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Controls exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed a weakening of that relationship. Conclusions Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between two brain systems often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia. PMID:20194482

One Month of Oral Morphine Decreases Gray Matter Volume in the Right Amygdala of Individuals with Low Back Pain: Confirmation of Previously Reported Magnetic Resonance Imaging Results.

PubMed

Lin, Joanne C; Chu, Larry F; Stringer, Elizabeth Ann; Baker, Katharine S; Sayyid, Zahra N; Sun, John; Campbell, Kelsey A; Younger, Jarred W

2016-08-01

Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings. Twenty-one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage. Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre-supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate. Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use. © 2015 American Academy of Pain Medicine.

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

PubMed

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

2009-07-15

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

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.

Sex differences in stress response circuitry activation dependent on female hormonal cycle.

PubMed

Goldstein, Jill M; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-13

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

Α4β2 and α7 nicotinic acetylcholine receptor binding predicts choice preference in two cost benefit decision-making tasks.

PubMed

Mendez, I A; Damborsky, J C; Winzer-Serhan, U H; Bizon, J L; Setlow, B

2013-01-29

Nicotinic receptors have been linked to a wide range of cognitive and behavioral functions, but surprisingly little is known about their involvement in cost benefit decision making. The goal of these experiments was to determine how nicotinic acetylcholine receptor (nAChR) expression is related to two forms of cost benefit decision making. Male Long Evans rats were tested in probability- and delay-discounting tasks, which required discrete trial choices between a small reward and a large reward associated with varying probabilities of omission and varying delays to reward delivery, respectively. Following testing, radioligand binding to α4β2 and α7 nAChR subtypes in brain regions implicated in cost benefit decision making was examined. Significant linear relationships were observed between choice of the large delayed reward in the delay discounting task and α4β2 receptor binding in both the dorsal and ventral hippocampus. Additionally, trends were found suggesting that choice of the large costly reward in both discounting tasks was inversely related to α4β2 receptor binding in the medial prefrontal cortex and nucleus accumbens shell. Similar trends suggested that choice of the large delayed reward in the delay discounting task was inversely related to α4β2 receptor binding in the orbitofrontal cortex, nucleus accumbens core, and basolateral amygdala, as well as to α7 receptor binding in the basolateral amygdala. These data suggest that nAChRs (particularly α4β2) play both unique and common roles in decisions that require consideration of different types of reward costs. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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

Deconstructing white matter connectivity of human amygdala nuclei with thalamus and cortex subdivisions in vivo.

PubMed

Abivardi, Aslan; Bach, Dominik R

2017-08-01

Structural alterations in long-range amygdala connections are proposed to crucially underlie several neuropsychiatric disorders. While progress has been made in elucidating the function of these connections, our understanding of their structure in humans remains sparse and non-systematic. Harnessing diffusion-weighted imaging and probabilistic tractography in humans, we investigate connections between two main amygdala nucleus groups, thalamic nuclei, and cortex. We first parcellated amygdala into deep (basolateral) and superficial (centrocortical) nucleus groups, and thalamus into six subregions, using previously established protocols based on connectivity. Cortex was parcellated based on T1-weighted images. We found substantial amygdala connections to thalamus, with different patterns for the two amygdala nuclei. Crucially, we describe direct subcortical connections between amygdala and paraventricular thalamus. Different from rodents but similar to non-human primates, these are more pronounced for basolateral than centrocortical amygdala. Substantial white-matter connectivity between amygdala and visual pulvinar is also more pronounced for basolateral amygdala. Furthermore, we establish detailed connectivity profiles for basolateral and centrocortical amygdala to cortical regions. These exhibit cascadic connections with sensory cortices as suggested previously based on tracer methods in non-human animals. We propose that the quantitative connectivity profiles provided here may guide future work on normal and pathological function of human amygdala. Hum Brain Mapp 38:3927-3940, 2017. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Deconstructing white matter connectivity of human amygdala nuclei with thalamus and cortex subdivisions in vivo

PubMed Central

2017-01-01

Abstract Structural alterations in long‐range amygdala connections are proposed to crucially underlie several neuropsychiatric disorders. While progress has been made in elucidating the function of these connections, our understanding of their structure in humans remains sparse and non‐systematic. Harnessing diffusion‐weighted imaging and probabilistic tractography in humans, we investigate connections between two main amygdala nucleus groups, thalamic nuclei, and cortex. We first parcellated amygdala into deep (basolateral) and superficial (centrocortical) nucleus groups, and thalamus into six subregions, using previously established protocols based on connectivity. Cortex was parcellated based on T1‐weighted images. We found substantial amygdala connections to thalamus, with different patterns for the two amygdala nuclei. Crucially, we describe direct subcortical connections between amygdala and paraventricular thalamus. Different from rodents but similar to non‐human primates, these are more pronounced for basolateral than centrocortical amygdala. Substantial white‐matter connectivity between amygdala and visual pulvinar is also more pronounced for basolateral amygdala. Furthermore, we establish detailed connectivity profiles for basolateral and centrocortical amygdala to cortical regions. These exhibit cascadic connections with sensory cortices as suggested previously based on tracer methods in non‐human animals. We propose that the quantitative connectivity profiles provided here may guide future work on normal and pathological function of human amygdala. Hum Brain Mapp 38:3927–3940, 2017. © 2017 Wiley Periodicals, Inc. PMID:28512761

Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI.

PubMed

Huang, Zhaoyang; Liang, Peipeng; Jia, Xiuqin; Zhan, Shuqin; Li, Ning; Ding, Yan; Lu, Jie; Wang, Yuping; Li, Kuncheng

2012-06-01

Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2016-07-01

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

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

PubMed Central

Lang, Simone; Kroll, Alexander; Lipinski, Slawomira J; Wessa, Michèle; Ridder, Stephanie; Christmann, Christoph; Schad, Lothar R; Flor, Herta

2009-01-01

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning. PMID:19200075

Reference frames for spatial frequency in face representation differ in the temporal visual cortex and amygdala.

PubMed

Inagaki, Mikio; Fujita, Ichiro

2011-07-13

Social communication in nonhuman primates and humans is strongly affected by facial information from other individuals. Many cortical and subcortical brain areas are known to be involved in processing facial information. However, how the neural representation of faces differs across different brain areas remains unclear. Here, we demonstrate that the reference frame for spatial frequency (SF) tuning of face-responsive neurons differs in the temporal visual cortex and amygdala in monkeys. Consistent with psychophysical properties for face recognition, temporal cortex neurons were tuned to image-based SFs (cycles/image) and showed viewing distance-invariant representation of face patterns. On the other hand, many amygdala neurons were influenced by retina-based SFs (cycles/degree), a characteristic that is useful for social distance computation. The two brain areas also differed in the luminance contrast sensitivity of face-responsive neurons; amygdala neurons sharply reduced their responses to low luminance contrast images, while temporal cortex neurons maintained the level of their responses. From these results, we conclude that different types of visual processing in the temporal visual cortex and the amygdala contribute to the construction of the neural representations of faces.

[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

The amygdala and ventromedial prefrontal cortex in morality and psychopathy.

PubMed

Blair, R J R

2007-09-01

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

Sex-related differences in amygdala functional connectivity during resting conditions.

PubMed

Kilpatrick, L A; Zald, D H; Pardo, J V; Cahill, L F

2006-04-01

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.

Repeated Exposure to Media Violence Is Associated with Diminished Response in an Inhibitory Frontolimbic Network

PubMed Central

Hirsch, Joy

2007-01-01

Background Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. Methodology/Principal Findings Using functional magnetic resonance imaging (fMRI), we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. Conclusions These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression. PMID:18060062

Emotion-based Dispositions to Rash Action: Positive and Negative Urgency

PubMed Central

Cyders, Melissa A.; Smith, Gregory T.

2008-01-01

Under heightened emotional states, individuals are more inclined to engage in ill-considered or rash actions than at other times. The authors present evidence for the existence of two related traits called positive and negative urgency. The traits refer to individual differences in the disposition to engage in rash action when experiencing extreme positive and negative affect, respectively. The authors provide evidence that these traits are distinct from other dispositions toward rash action, and that they play distinct roles in predicting problem levels of involvement in behaviors such as alcohol consumption, binge eating, drug use, and risky sexual behavior. The authors identify facilitative conditions for the emergence of the urgency traits from neuroscience. Certain gene polymorphisms are associated with low levels of serotonin and high levels of dopamine; that pattern of neurotransmitter activity in a brain system linking the orbitofrontal cortex and the amygdala appears to facilitate development of positive and negative urgency. The authors discuss the implications of this theory. PMID:18954158

Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods

PubMed Central

Killgore, William D. S.; Ross, Amy J.; Kamiya, Toshi; Kawada, Yoko; Renshaw, Perry F.; Yurgelun-Todd, Deborah A.

2011-01-01

Cytidine-5’-diphosphocholine (citicoline) has a variety of cognitive enhancing, neuroprotective, and neuroregenerative properties. In cocaine-addicted individuals, citicoline has been shown to increase brain dopamine levels and reduce cravings. The effects of this compound on appetite, food cravings, and brain responses to food are unknown. We compared the effects of treatment with citicoline (500 mg/day versus 2000 mg/day) for six weeks on changes in appetite ratings, weight, and cortico-limbic responses to images of high calorie foods using functional magnetic resonance imaging (fMRI). After six weeks, there was no significant change in weight status, although significant declines in appetite ratings were observed for the 2000 mg/day group. The higher dose group also showed significant increases in functional brain responses to food stimuli within the amygdala, insula, and lateral orbitofrontal cortex. Increased activation in these regions correlated with declines in appetite ratings. These preliminary findings suggest a potential usefulness of citicoline in modulating appetite, but further research is warranted. PMID:19260039

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

Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice

PubMed Central

Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.

2012-01-01

Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

PubMed

Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

2016-10-01

Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Posterior Medial Cortex in Urologic Chronic Pelvic Pain Syndrome: Detachment from Default Mode Network. A Resting-State Study from the MAPP Research Network

PubMed Central

Martucci, Katherine T.; Shirer, William R.; Bagarinao, Epifanio; Johnson, Kevin A.; Farmer, Melissa A.; Labus, Jennifer S.; Apkarian, A. Vania; Deutsch, Georg; Harris, Richard E.; Mayer, Emeran A.; Clauw, Daniel J.; Greicius, Michael D.; Mackey, Sean C.

2015-01-01

Altered resting-state brain activity, as a measure of functional connectivity, is commonly observed in chronic pain. Identifying a reliable signature pattern of altered resting-state activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed resting-state fMRI data from female patients with urologic chronic pelvic pain syndrome (UCPPS, N = 45) and matched healthy participants (N = 45) as part of a NIDDK funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased functional connectivity of the default mode network (DMN) to two regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and left precuneus (TFCE, FWE corrected p<0.05). Further investigation revealed that patients demonstrated increased functional connectivity between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (e.g., insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased functional connectivity to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships and self-esteem levels in patients. Collectively, these findings indicate that in UCPPS patients, regions of the PMC are detached from the DMN, while neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes. PMID:26010458

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

Brain activity in hunger and satiety: an exploratory visually stimulated FMRI study.

PubMed

Führer, Dagmar; Zysset, Stefan; Stumvoll, Michael

2008-05-01

To explore neuroanatomical sites of eating behavior, we have developed a simple functional magnetic resonance imaging (fMRI) paradigm to image hunger vs. satiety using visual stimulation. Twelve healthy, lean, nonsmoking male subjects participated in this study. Pairs of food-neutral and food-related pictures were presented in a block design, after a 14-h fast and 1 h after ad libitum ingestion of a mixed meal. Statistically, a general linear model for serially autocorrelated observations with a P level<0.001 was used. During the hunger condition, significantly enhanced brain activity was found in the left striate and extrastriate cortex, the inferior parietal lobe, and the orbitofrontal cortices. Stimulation with food images was associated with increased activity in both insulae, the left striate and extrastriate cortex, and the anterior midprefrontal cortex. Nonfood images were associated with enhanced activity in the right parietal lobe and the left and right middle temporal gyrus. A significant interaction in activation pattern between the states of hunger and satiety and stimulation with food and nonfood images was found for the left anterior cingulate cortex, the superior occipital sulcus, and in the vicinity of the right amygdala. These preliminary data from a homogenous healthy male cohort suggest that central nervous system (CNS) activation is not only altered with hunger and satiety but that food and nonfood images have also specific effects on regional brain activity if exposure takes place in different states of satiety. Wider use of our or a similar approach would help to establish a uniform paradigm to map hunger and satiety to be used for further experiments.

[Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia].

PubMed

Reshetniak, V K; Kukushkin, M L

1989-07-01

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.

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,…

Sex differences in amygdala activation during the perception of facial affect.

PubMed

Killgore, W D; Yurgelun-Todd, D A

2001-08-08

The cognitive and affective systems of the cerebral cortex are often more lateralized in males than females, but it is unclear whether these differences extend to subcortical systems. We used fMRI to examine sex differences in lateralized amygdala activity during happy and fearful face perception. Amygdala activation differed for men and women depending on the valence of the expression. Overall, males were more lateralized than females, but the direction differed between valence conditions. Happy faces produced greater right than left amygdala activation for males but not females. Both sexes showed greater left amygdala activation for fearful faces. These findings suggest that the lateralization of affective function may extend beyond the cortex to subcortical regions such as the amygdala.

The structural neuroanatomy of music emotion recognition: Evidence from frontotemporal lobar degeneration

PubMed Central

Omar, Rohani; Henley, Susie M.D.; Bartlett, Jonathan W.; Hailstone, Julia C.; Gordon, Elizabeth; Sauter, Disa A.; Frost, Chris; Scott, Sophie K.; Warren, Jason D.

2011-01-01

Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions. PMID:21385617

Neuroimaging and obesity: current knowledge and future directions

PubMed Central

Carnell, S.; Gibson, C.; Benson, L.; Ochner, C. N.; Geliebter, A.

2011-01-01

Summary Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications. PMID:21902800

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.

The structural neuroanatomy of music emotion recognition: evidence from frontotemporal lobar degeneration.

PubMed

Omar, Rohani; Henley, Susie M D; Bartlett, Jonathan W; Hailstone, Julia C; Gordon, Elizabeth; Sauter, Disa A; Frost, Chris; Scott, Sophie K; Warren, Jason D

2011-06-01

Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

PubMed Central

Hayes, Dave J.; Northoff, Georg

2011-01-01

The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed. PMID:22102836

Neural correlates of social cooperation and non-cooperation as a function of psychopathy.

PubMed

Rilling, James K; Glenn, Andrea L; Jairam, Meeta R; Pagnoni, Giuseppe; Goldsmith, David R; Elfenbein, Hanie A; Lilienfeld, Scott O

2007-06-01

Psychopathy is a disorder involving a failure to experience many emotions that are necessary for appropriate social behavior. In this study, we probed the behavioral, emotional, and neural correlates of psychopathic traits within the context of a dyadic social interaction. Thirty subjects were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma game with human confederates who were outside the scanner. Subjects also completed two self-report psychopathy questionnaires. Subjects scoring higher on psychopathy, particularly males, defected more often and were less likely to continue cooperating after establishing mutual cooperation with a partner. Further, they experienced more outcomes in which their cooperation was not reciprocated (cooperate-defect outcome). After such outcomes, subjects scoring high in psychopathy showed less amygdala activation, suggesting weaker aversive conditioning to those outcomes. Compared with low-psychopathy subjects, subjects higher in psychopathy also showed weaker activation within orbitofrontal cortex when choosing to cooperate and showed weaker activation within dorsolateral prefrontal and rostral anterior cingulate cortex when choosing to defect. These findings suggest that whereas subjects scoring low on psychopathy have emotional biases toward cooperation that can only be overcome with effortful cognitive control, subjects scoring high on psychopathy have an opposing bias toward defection that likewise can only be overcome with cognitive effort.

Zinc release in the lateral nucleus of the amygdala by stimulation of the entorhinal cortex.

PubMed

Takeda, Atsushi; Imano, Sachie; Itoh, Hiromasa; Oku, Naoto

2006-11-06

Zinc release in the lateral nucleus of the amygdala was examined using rat brain slices. The lateral and basolateral nuclei in the amygdala were evidently stained by Timm's sulfide-silver staining method. When the amygdala including both the nuclei was stimulated with 100 mM KCl by means of in vivo microdialysis, extracellular zinc concentration was increased significantly. Zinc release in the lateral nucleus of the amygdala innervated by the entorhinal cortex was next examined in brain slices double-stained with zinc and calcium indicators. Extracellular zinc signal (ZnAF-2) in the lateral nucleus was increased with intracellular calcium signal (calcium orange) during delivery of tetanic stimuli to the entorhinal cortex. Both the increases were completely inhibited by addition of 1 micro M tetrodotoxin, a sodium channel blocker. Furthermore, calcium signal in the lateral nucleus during delivery of tetanic stimuli to the entorhinal cortex was increased in the presence of 10 micro M CNQX, an AMPA/KA receptor antagonist, and this increase was facilitated by addition of 1 mM CaEDTA, a membrane-impermeable zinc chelator. The present study suggested that zinc is released in the lateral nucleus of the amygdala by depolarization of the entorhinal neurons. In the lateral nucleus, zinc released may suppress the increase in presynaptic calcium signal.

[Comparative study of effects of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats].

PubMed

Nersesian, L B; Eganova, V S; Pogosian, N L; Avetisian, I N

2011-01-01

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons on stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce on the activity of medullar respiratory neurons both facilitating and inhibitory action with predominance of the activating one (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions--at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.

Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia.

PubMed

Satterthwaite, Theodore D; Wolf, Daniel H; Loughead, James; Ruparel, Kosha; Valdez, Jeffrey N; Siegel, Steven J; Kohler, Christian G; Gur, Raquel E; Gur, Ruben C

2010-04-01

Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship. Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia.

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.

Functional brain correlates of heterosexual paedophilia.

PubMed

Schiffer, Boris; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Kruger, Tillmann H C

2008-05-15

Although the neuronal mechanisms underlying normal sexual motivation and function have recently been examined, the alterations in brain function in deviant sexual behaviours such as paedophilia are largely unknown. The objective of this study was to identify paedophilia-specific functional networks implicated in sexual arousal. Therefore a consecutive sample of eight paedophile forensic inpatients, exclusively attracted to females, and 12 healthy age-matched heterosexual control participants from a comparable socioeconomic stratum participated in a visual sexual stimulation procedure during functional magnetic resonance imaging. The visual stimuli were sexually stimulating photographs and emotionally neutral photographs. Immediately after the imaging session subjective responses pertaining to sexual desire were recorded. Principally, the brain response of heterosexual paedophiles to heteropaedophilic stimuli was comparable to that of heterosexual males to heterosexual stimuli, including different limbic structures (amygdala, cingulate gyrus, and hippocampus), the substantia nigra, caudate nucleus, as well as the anterior cingulate cortex, different thalamic nuclei, and associative cortices. However, responses to visual sexual stimulation were found in the orbitofrontal cortex in healthy heterosexual males, but not in paedophiles, in whom abnormal activity in the dorsolateral prefrontal cortex was observed. Thus, in line with clinical observations and neuropsychological studies, it seems that central processing of sexual stimuli in heterosexual paedophiles may be altered by a disturbance in the prefrontal networks, which, as has already been hypothesized, may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours. Moreover, these findings may suggest a dysfunction (in the functional and effective connectivity) at the cognitive stage of sexual arousal processing.

Odor-induced recall of emotional memories in PTSD-Review and new paradigm for research.

PubMed

Daniels, Judith K; Vermetten, Eric

2016-10-01

It is clinically well known that olfactory intrusions in PTSD can be a disabling phenomena due to the involuntary recall of odor memories. Odorants can trigger involuntary recall of emotional memories as well have the potential to help diminishing emotional arousal as grounding stimuli. Despite major advances in our understanding of the function of olfactory system, the study of the relation of olfaction and emotional memory is still relatively scarce. Odor memory is long thought to be different than other types of memories such as verbal or visual memories, being more strongly engraved and more closely related to strong emotions. Brain areas mediating smell memory including orbitofrontal cortex and other parts of medial prefrontal cortex, hippocampus and amygdala, have been implicated in learning and memory and are part of a neural circuitry that is involved in PTSD. The olfactory cortex itself also plays an important role in emotional processing. Clinical observations support the notion that odor-evoked memories can play a role in the symptomatology of PTSD. This paper reviews a re-emerging body of science linking odor processing to emotional processing in PTSD using the calming and grounding effect of odors as well as the use of odors in augmented exposure therapy. This results in converging evidence that olfaction is an excellent model for studying many questions germane to the field of human emotional memory processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered regional cortical thickness and subcortical volume in women with primary dysmenorrhoea.

PubMed

Liu, P; Yang, J; Wang, G; Liu, Y; Liu, X; Jin, L; Liang, F; Qin, W; Calhoun, V D

2016-04-01

There is emerging evidence that primary dysmenorrhoea (PDM) is associated with altered brain function and structure. However, few studies have investigated changes in regional cortical thickness and subcortical volumes in PDM patients. The purpose of this study was to characterize differences in both cortical thickness and subcortical volumes between PDM patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 PDM patients and 32 HCs matched for age and handedness. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Correlation analysis was then used to evaluate relationships between the clinical symptoms and abnormal brain structure in PDM. PDM patients had significantly increased cortical thickness in the orbitofrontal cortex (OFC), insula (IN), primary/secondary sensory area (SI/SII), superior temporal cortex (STC), precuneus (pCUN) and posterior cingulate cortex (PCC). Meanwhile, significantly decreased subcortical volumes of the caudate, thalamus and amygdala were found in PDM patients. Moreover, there were significant positive correlations between the PDM-related duration and the OFC, SFC, STC and IN. The MPQ scores were positively correlated with the pCUN. These findings provide further evidence for grey matter changes in patients with PDM, and in addition, the results support relationships between the structural abnormalities and their role in symptom production. All these results are likely to be potential valuable to provide us with direct information about the neural basis of PDM. © 2015 European Pain Federation - EFIC®

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.

Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques.

PubMed

Rogers, Christina N; Ross, Amy P; Sahu, Shweta P; Siegel, Ethan R; Dooyema, Jeromy M; Cree, Mary Ann; Stopa, Edward G; Young, Larry J; Rilling, James K; Albers, H Elliott; Preuss, Todd M

2018-05-24

Oxytocin (OT) and arginine-vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non-human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT- and AVP-producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself. However, OT and AVP also influence social cognition, including effects on social recognition, cooperation, communication, and in-group altruism, which suggests connectivity with cortical structures. While OT and AVP V1a receptors have been demonstrated in the cortex of rodents and primates, and intranasal administration of OT and AVP has been shown to modulate cortical activity, there is to date little evidence that OT-and AVP-containing neurons project into the cortex. Here, we demonstrate the existence of OT- and AVP-containing fibers in cortical regions relevant to social cognition using immunohistochemistry in humans, chimpanzees, and rhesus macaques. OT-immunoreactive fibers were found in the straight gyrus of the orbitofrontal cortex as well as the anterior cingulate gyrus in human and chimpanzee brains, while no OT-immunoreactive fibers were found in macaque cortex. AVP-immunoreactive fibers were observed in the anterior cingulate gyrus in all species, as well as in the insular cortex in humans, and in a more restricted distribution in chimpanzees. This is the first report of OT and AVP fibers in the cortex in human and non-human primates. Our findings provide a potential mechanism by which OT and AVP might exert effects on brain regions far from their production site in the hypothalamus, as well as potential species differences in the behavioral functions of these target regions. © 2018 Wiley Periodicals, Inc.

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

PubMed Central

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors. PMID:28066196

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

PubMed

Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors.

Amygdala-prefrontal cortex resting-state functional connectivity varies with first depressive or manic episode in bipolar disorder.

PubMed

Wei, Shengnan; Geng, Haiyang; Jiang, Xiaowei; Zhou, Qian; Chang, Miao; Zhou, Yifang; Xu, Ke; Tang, Yanqing; Wang, Fei

2017-02-22

Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (p<0.05, corrected). In addition, rsFC between the amygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (p<0.05, corrected). Our findings suggest that mood state during the first episodes of BD may be related to abnormality in hemispheric lateralization. The abnormalities in amygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders.

PubMed

Hafeman, Danella; Bebko, Genna; Bertocci, Michele A; Fournier, Jay C; Chase, Henry W; Bonar, Lisa; Perlman, Susan B; Travis, Michael; Gill, Mary Kay; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Arnold, L Eugene; Fristad, Mary A; Frazier, Thomas W; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2017-01-15

Both bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task. We scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex. FxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions

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

ERIC Educational Resources Information Center

Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

2012-01-01

Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

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.

Neural systems for social cognition: gray matter volume abnormalities in boys at high genetic risk of autism symptoms, and a comparison with idiopathic autism spectrum disorder.

PubMed

Goddard, Marcia N; Swaab, Hanna; Rombouts, Serge A R B; van Rijn, Sophie

2016-09-01

Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies.

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.

Induction of c-Fos immunoreactivity in the amygdala of mice expressing anxiety-like behavior after local perfusion of veratrine in the prelimbic medial prefrontal cortex.

PubMed

Yamada, Misa; Saitoh, Akiyoshi; Ohashi, Masanori; Suzuki, Satoshi; Oka, Jun-Ichiro; Yamada, Mitsuhiko

2015-08-01

Local perfusion of the sodium channel activator veratrine in mouse prelimbic medial prefrontal cortex (PL) induced c-Fos immunoreactivity in the sub-regions of amygdala. Co-perfusion of the NMDA receptor antagonist MK-801 diminished the c-Fos expression. Significant correlations were observed between c-Fos immunoreactivity and behavioral measures in the open-field test. The PL stimulation activates a neural network projecting to the amygdala via NMDA receptor-mediated glutamatergic neurotransmission. Anxiety-like behavior induced after the PL stimulation may be partly mediated through the activation of amygdala.

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.

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.

Amygdala-cingulate intrinsic connectivity is associated with degree of social inhibition

PubMed Central

Blackford, Jennifer Urbano; Clauss, Jacqueline A.; Avery, Suzanne N.; Cowan, Ronald L.; Benningfield, Margaret M.; VanDerKlok, Ross M.

2014-01-01

The tendency to approach or avoid novel people is a fundamental human behavior and is a core dimension of social anxiety. Resting state fMRI was used to test for an association between social inhibition and intrinsic connectivity in 40 young adults ranging from low to high in social inhibition. Higher levels of social inhibition were associated with specific patterns of reduced amygdala-cingulate cortex connectivity. Connectivity was reduced between the superficial amygdala and the rostral cingulate cortex and between the centromedial amygdala and the dorsal anterior cingulate cortex. Social inhibition also modulated connectivity in several well-established intrinsic networks; higher social inhibition correlated with reduced connectivity with default mode and dorsal attention networks and enhanced connectivity in salience and executive control networks. These findings provide important preliminary evidence that social inhibition reflects differences in the underlying intrinsic connectivity of the brain in the absence of social stimuli or stressors. PMID:24534162

Cocaine. Selective regional effects on central monoamines.

PubMed

Hadfield, M G

1995-01-01

Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice ip. Thirty minutes later, the brains were removed, and nine regions were isolated: olfactory bulbs, olfactory tubercles, prefrontal cortex, septum, striatum, amygdala, hypothalamus, hippocampus, and thalamus. Using high-performance liquid chromatography, concentrations of norepinephrine, dopamine, serotonin, and their major metabolites and the metabolite/neurotransmitter ratios were determined as an indicator of utilization. Serotonergic systems responded most dramatically. 5HIAA/5-HT decreases were seen in all the brain regions, except the septum, hippocampus, and olfactory bulbs. In most instances, the alterations were dose-dependent. The most profound changes were seen in the amygdala, prefrontal cortex, hypothalamus, and thalamus. For noradrenergic systems, significant responses were seen only in the amygdala, prefrontal cortex, and hypothalamus, but then only at the lower dose. The dopaminergic responses were more complex and not always dose-dependent. The DOPAC/DA ratio was decreased only in the amygdala and striatum at the lower dose, and the olfactory tubercles at the higher dose. It was increased in the septum. The HVA/DA ratios were decreased in the amygdala, prefrontal cortex, and hypothalamus, but only at the lower dose (like MHPG/NE). The 3MT/DA ratio was decreased in the thalamus at the lower dose and in the olfactory tubercles at the higher dose, whereas it was increased in the prefrontal cortex at the lower dose. The HVA and DOPAC routes of degradation were both utilized only by the amygdala. Thus, cocaine produced its most comprehensive effects in this nucleus, as well as the greatest absolute percentage changes for all three of the monoamine systems studied.

The drive to strive: goal generation based on current needs

PubMed Central

Murray, Elisabeth A.; Rudebeck, Peter H.

2013-01-01

Hungry animals are influenced by a multitude of different factors when foraging for sustenance. Much of the work on animal foraging has focused on factors relating to the amount of time and energy animals expend searching for and harvesting foods. Models that emphasize such factors have been invaluable in determining when it is beneficial for an animal to search for pastures new. When foraging, however, animals also have to determine how to direct their search. For what food should they forage? There is no point searching for more of a particular food when you are sated from eating it. Here we review work in macaques and humans that has sought to reveal the neural circuits critical for determining the subjective value of different foods and associated objects in our environment and tracking this value over time. There is mounting evidence that a network composed of the orbitofrontal cortex (OFC), amygdala, and medial thalamus is critical for linking objects in the environment with food value and adjusting those valuations in real time based on current biological needs. Studies using temporary inactivation methods have revealed that the amygdala and OFC play distinct yet complementary roles in this valuation process. Such a network for determining the subjective value of different foods and, by extension, associated objects, must interact with systems that determine where and for how long to forage. Only by efficiently incorporating these two factors into their decisions will animals be able to achieve maximal fitness. PMID:23818876

Developmental alterations in anxiety and cognitive behavior in serotonin transporter mutant mice.

PubMed

Sakakibara, Yasufumi; Kasahara, Yoshiyuki; Hall, F Scott; Lesch, Klaus-Peter; Murphy, Dennis L; Uhl, George R; Sora, Ichiro

2014-10-01

A promoter variant of the serotonin transporter (SERT) gene is known to affect emotional and cognitive regulation. In particular, the "short" allelic variant is implicated in the etiology of multiple neuropsychiatric disorders. Heterozygous (SERT(+/-)) and homozygous (SERT(-/-)) SERT mutant mice are valuable tools for understanding the mechanisms of altered SERT levels. Although these genetic effects are well investigated in adulthood, the developmental trajectory of altered SERT levels for behavior has not been investigated. We assessed anxiety-like and cognitive behaviors in SERT mutant mice in early adolescence and adulthood to examine the developmental consequences of reduced SERT levels. Spine density of pyramidal neurons was also measured in corticolimbic brain regions. Adult SERT(-/-) mice exhibited increased anxiety-like behavior, but these differences were not observed in early adolescent SERT(-/-) mice. Conversely, SERT(+/-) and SERT(-/-) mice did display higher spontaneous alternation during early adolescence and adulthood. SERT(+/-) and SERT(-/-) also exhibited greater neuronal spine densities in the orbitofrontal but not the medial prefrontal cortices. Adult SERT(-/-) mice also showed an increased spine density in the basolateral amygdala. Developmental alterations of the serotonergic system caused by genetic inactivation of SERT can have different influences on anxiety-like and cognitive behaviors through early adolescence into adulthood, which may be associated with changes of spine density in the prefrontal cortex and amygdala. The altered maturation of serotonergic systems may lead to specific age-related vulnerabilities to psychopathologies that develop during adolescence.

Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity

PubMed Central

Lapate, R. C.; Rokers, B.; Tromp, D. P. M.; Orfali, N. S.; Oler, J. A.; Doran, S. T.; Adluru, N.; Alexander, A. L.; Davidson, R. J.

2016-01-01

Conscious awareness of negative cues is thought to enhance emotion-regulatory capacity, but the neural mechanisms underlying this effect are unknown. Using continuous flash suppression (CFS) in the MRI scanner, we manipulated visual awareness of fearful faces during an affect misattribution paradigm, in which preferences for neutral objects can be biased by the valence of a previously presented stimulus. The amygdala responded to fearful faces independently of awareness. However, when awareness of fearful faces was prevented, individuals with greater amygdala responses displayed a negative bias toward unrelated novel neutral faces. In contrast, during the aware condition, inverse coupling between the amygdala and prefrontal cortex reduced this bias, particularly among individuals with higher structural connectivity in the major white matter pathway connecting the prefrontal cortex and amygdala. Collectively, these results indicate that awareness promotes the function of a critical emotion-regulatory network targeting the amygdala, providing a mechanistic account for the role of awareness in emotion regulation. PMID:27181344

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.

Age-Related Changes in Amygdala-Frontal Connectivity during Emotional Face Processing from Childhood into Young Adulthood

PubMed Central

Wu, Minjie; Kujawa, Autumn; Lu, Lisa H.; Fitzgerald, Daniel A.; Klumpp, Heide; Fitzgerald, Kate D.; Monk, Christopher S.; Phan, K. Luan

2016-01-01

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age-related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful and happy faces) in 61 healthy subjects aged 7–25 years. We found age-related decreases in ventral medial prefrontal cortex (vmPFC) activity in response to happy faces but not to angry or fearful faces, and an age-related change (shifting from positive to negative correlation) in amygdala-anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom-up amygdala excitatory signaling to ACC/mPFC in children and later development of top-down inhibitory control of ACC/mPFC over amygdala in adults. Age-related changes in amygdala-ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala-ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat-specific processing. PMID:26931629

Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect

PubMed Central

Teicher, Martin H.; Samson, Jacqueline A.

2015-01-01

Background and Scope Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A key breakthrough has been the discovery that maltreatment alters trajectories of brain development. This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress-induced damage. Findings Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable. Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Conclusion Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies. PMID:26831814

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.

Structural and functional neural correlates of music perception.

PubMed

Limb, Charles J

2006-04-01

This review article highlights state-of-the-art functional neuroimaging studies and demonstrates the novel use of music as a tool for the study of human auditory brain structure and function. Music is a unique auditory stimulus with properties that make it a compelling tool with which to study both human behavior and, more specifically, the neural elements involved in the processing of sound. Functional neuroimaging techniques represent a modern and powerful method of investigation into neural structure and functional correlates in the living organism. These methods have demonstrated a close relationship between the neural processing of music and language, both syntactically and semantically. Greater neural activity and increased volume of gray matter in Heschl's gyrus has been associated with musical aptitude. Activation of Broca's area, a region traditionally considered to subserve language, is important in interpreting whether a note is on or off key. The planum temporale shows asymmetries that are associated with the phenomenon of perfect pitch. Functional imaging studies have also demonstrated activation of primitive emotional centers such as ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex in listeners of moving musical passages. In addition, studies of melody and rhythm perception have elucidated mechanisms of hemispheric specialization. These studies show the power of music and functional neuroimaging to provide singularly useful tools for the study of brain structure and function.

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

PubMed

Blair, R J R

2008-08-12

The current paper examines the functional contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) and the evidence that the functioning of these systems is compromised in individuals with psychopathy. The amygdala is critical for the formation of stimulus-reinforcement associations, both punishment and reward based, and the processing of emotional expressions. vmPFC is critical for the representation of reinforcement expectancies and, owing to this, decision making. Neuropsychological and neuroimaging data from individuals with psychopathy are examined. It is concluded that these critical functions of the amygdala and vmPFC, and their interaction, are compromised in individuals with the disorder. It is argued that these impairments lead to the development of psychopathy.

Menstrual cycle phase modulates reward-related neural function in women.

PubMed

Dreher, Jean-Claude; Schmidt, Peter J; Kohn, Philip; Furman, Daniella; Rubinow, David; Berman, Karen Faith

2007-02-13

There is considerable evidence from animal studies that the mesolimbic and mesocortical dopamine systems are sensitive to circulating gonadal steroid hormones. Less is known about the influence of estrogen and progesterone on the human reward system. To investigate this directly, we used functional MRI and an event-related monetary reward paradigm to study women with a repeated-measures, counterbalanced design across the menstrual cycle. Here we show that during the midfollicular phase (days 4-8 after onset of menses) women anticipating uncertain rewards activated the orbitofrontal cortex and amygdala more than during the luteal phase (6-10 days after luteinizing hormone surge). At the time of reward delivery, women in the follicular phase activated the midbrain, striatum, and left fronto-polar cortex more than during the luteal phase. These data demonstrate augmented reactivity of the reward system in women during the midfollicular phase when estrogen is unopposed by progesterone. Moreover, investigation of between-sex differences revealed that men activated ventral putamen more than women during anticipation of uncertain rewards, whereas women more strongly activated the anterior medial prefrontal cortex at the time of reward delivery. Correlation between brain activity and gonadal steroid levels also revealed that the amygdalo-hippocampal complex was positively correlated with estradiol level, regardless of menstrual cycle phase. Together, our findings provide evidence of neurofunctional modulation of the reward system by gonadal steroid hormones in humans and establish a neurobiological foundation for understanding their impact on vulnerability to drug abuse, neuropsychiatric diseases with differential expression across males and females, and hormonally mediated mood disorders.

Novel bio-inspired smart control for hazard mitigation of civil structures

NASA Astrophysics Data System (ADS)

Kim, Yeesock; Kim, Changwon; Langari, Reza

2010-11-01

In this paper, a new bio-inspired controller is proposed for vibration mitigation of smart structures subjected to ground disturbances (i.e. earthquakes). The control system is developed through the integration of a brain emotional learning (BEL) algorithm with a proportional-integral-derivative (PID) controller and a semiactive inversion (Inv) algorithm. The BEL algorithm is based on the neurologically inspired computational model of the amygdala and the orbitofrontal cortex. To demonstrate the effectiveness of the proposed hybrid BEL-PID-Inv control algorithm, a seismically excited building structure equipped with a magnetorheological (MR) damper is investigated. The performance of the proposed hybrid BEL-PID-Inv control algorithm is compared with that of passive, PID, linear quadratic Gaussian (LQG), and BEL control systems. In the simulation, the robustness of the hybrid BEL-PID-Inv control algorithm in the presence of modeling uncertainties as well as external disturbances is investigated. It is shown that the proposed hybrid BEL-PID-Inv control algorithm is effective in improving the dynamic responses of seismically excited building structure-MR damper systems.

Gender differences in emotional responses: a psychophysiological study.

PubMed

Bianchin, Marta; Angrilli, Alessandro

2012-02-28

Gender differences in emotional responses have been investigated in two groups of students, 22 males and 21 females. Participants watched a set of sixty emotional standardized slides divided into pleasant, neutral and unpleasant, while Startle reflex, Evoked Potentials, Heart Rate, facial EMG and Skin Conductance were recorded. Startle reflex amplitude, an index modulated by amygdala and orbitofrontal cortex and sensitive to aversive emotional stimuli, was overall larger in women. In addition, startle emotion modulation was greater in women with respect to men. Slow Evoked Potentials (400-800 ms), a measure representing the cognitive component of the emotional response, revealed gender differences in the left prefrontal site, with women showing greater positivity to unpleasant compared with pleasant slides while men had greater positivity to pleasant vs. neutral slides. Women, compared with men, perceived all slides as less pleasant and reported greater arousal to unpleasant condition. Results are in line with known functional brain differences, at level of limbic and paralimbic structures, between men and women, and point to biologically grounded greater sensitivity and vulnerability of women to adverse/stressful events. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of systemic cholinergic antagonism on reinforcer devaluation in macaques.

PubMed

Waguespack, Hannah F; Málková, Ludise; Forcelli, Patrick A; Turchi, Janita

2018-06-21

The capacity to adjust actions based on new information is a vital cognitive function. An animal's ability to adapt behavioral responses according to changes in reward value can be measured using a reinforcer devaluation task, wherein the desirability of a given object is reduced by decreasing the value of the associated food reinforcement. Elements of the neural circuits serving this ability have been studied in both rodents and nonhuman primates. Specifically, the basolateral amygdala, orbitofrontal cortex, nucleus accumbens, and mediodorsal thalamus have each been shown to play a critical role in the process of value updating, required for adaptive goal selection. As these regions receive dense cholinergic input, we investigated whether systemic injections of non-selective nicotinic or muscarinic acetylcholine receptor antagonists, mecamylamine and scopolamine, respectively, would impair performance on a reinforcer devaluation task. Here we demonstrate that in the presence of either a nicotinic or muscarinic antagonist, animals are able to shift their behavioral responses in an appropriate manner, suggesting that disruption of cholinergic neuromodulation is not sufficient to disrupt value updating, and subsequent goal selection, in rhesus macaques. Published by Elsevier B.V.

Clinical characterization of bvFTD due to FUS neuropathology

PubMed Central

Lee, Suzee E.; Seeley, William W.; Poorzand, Pardis; Rademakers, Rosa; Karydas, Anna; Stanley, Christine M.; Miller, Bruce L.; Rankin, Katherine P.

2011-01-01

In 2009, inclusions containing the fused in sarcoma (FUS) protein were identified as a third major molecular class of pathology underlying the behavioral variant frontotemporal dementia (bvFTD) syndrome. Due to the low prevalence of FUS pathology, few clinical descriptions have been published and none provides information about specific social-emotional deficits despite evidence for severe behavioral manifestations in this disorder. We evaluated a patient with bvFTD due to FUS pathology using a comprehensive battery of cognitive and social-emotional tests. A structural MRI scan and genetic tests for tau, progranulin, and FUS mutations were also performed. The patient showed preserved general cognitive functioning and superior working memory, but severe deficits in emotion attribution, sensitivity to punishment, and the capacity for interpersonal warmth and empathy. The gray matter atrophy pattern corresponded to this focal deficit profile, with preservation of dorsolateral fronto-parietal regions associated with executive functioning but severe damage to right worse than left frontoinsula, temporal pole, subgenual anterior cingulate, medial orbitofrontal cortex, amygdala, and caudate. This patient demonstrates the striking focality associated with FUS neuropathology in patients with bvFTD. PMID:22060063

Differential Hemodynamic Response in Affective Circuitry with Aging: An fMRI Study of Novelty, Valence, and Arousal

PubMed Central

Moriguchi, Yoshiya; Negreira, Alyson; Weierich, Mariann; Dautoff, Rebecca; Dickerson, Bradford C.; Wright, Christopher I.; Barrett, Lisa Feldman

2011-01-01

Emerging evidence indicates that stimulus novelty is affectively potent and reliably engages the amygdala and other portions of the affective workspace in the brain. Using fMRI, we examined whether novel stimuli remain affectively salient across the lifespan, and therefore, whether novelty processing—a potentially survival-relevant function—is preserved with aging. Nineteen young and 22 older healthy adults were scanned during observing novel and familiar affective pictures while estimating their own subjectively experienced aroused levels. We investigated age-related difference of magnitude of activation, hemodynamic time course, and functional connectivity of BOLD responses in the amygdala. Although there were no age-related differences in the peak response of the amygdala to novelty, older individuals showed a narrower, sharper (i.e., “peakier”) hemodynamic time course in response to novel stimuli, as well as decreased connectivity between the left amygdala and the affective areas including orbito-frontal regions. These findings have relevance for understanding age-related differences in memory and affect regulation. PMID:20521849

Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala

PubMed Central

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

2010-01-01

Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of ‘self’ underlies the core disorder in MDD; the medial frontal cortex represents ‘self’; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. PMID:21111403

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

PubMed Central

Felicio, Andre C.; Dinelle, Katherine; Agarwal, Pankaj A.; McKenzie, Jessamyn; Heffernan, Nicole; Road, Jeremy D.; Appel-Cresswell, Silke; Wszolek, Zbigniew K.; Farrer, Matthew J.; Schulzer, Michael; Sossi, Vesna; Stoessl, A. Jon

2014-01-01

Introduction We have used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. Methods All subjects had brain imaging using 18F-6-fluoro-L-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter). Results FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate and left ventral striatum. Conclusions Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene. PMID:24797316

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

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

Reward Systems in the Brain and Nutrition.

PubMed

Rolls, Edmund T

2016-07-17

The taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are combined by associative learning with olfactory and visual inputs for some neurons, and these neurons encode food reward value in that they respond to food only when hunger is present 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, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex. These food reward representations are important in the control of appetite and food intake. Individual differences in reward representations may contribute to obesity, and there are age-related differences in these reward representations. Implications of how reward systems in the brain operate for understanding, preventing, and treating obesity are described.

Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.

PubMed

Nitschke, Jack B; Sarinopoulos, Issidoros; Oathes, Desmond J; Johnstone, Tom; Whalen, Paul J; Davidson, Richard J; Kalin, Ned H

2009-03-01

The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response

PubMed Central

Nitschke, Jack B.; Sarinopoulos, Issidoros; Oathes, Desmond J.; Johnstone, Tom; Whalen, Paul J.; Davidson, Richard J.; Kalin, Ned H.

2009-01-01

Objective The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Method Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Results Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. Conclusions These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder. PMID:19122007

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…

Neural mechanisms of anger regulation as a function of genetic risk for violence.

PubMed

Alia-Klein, Nelly; Goldstein, Rita Z; Tomasi, Dardo; Woicik, Patricia A; Moeller, Scott J; Williams, Benjamin; Craig, Ian W; Telang, Frank; Biegon, Anat; Wang, Gene-Jack; Fowler, Joanna S; Volkow, Nora D

2009-06-01

Genetic risk may predispose individuals to compromised anger regulation, potentially through modulation of brain responses to emotionally evocative stimuli. Emphatically expressed, the emotional word No can prohibit behavior through conditioning. In a recent functional magnetic resonance imaging study, the authors showed that healthy males attribute negative valence to No while showing a lateral orbitofrontal response that correlated with their self-reported anger control. Here, the authors examined the influence of the monoamine oxidase A (MAOA) gene (low vs. high transcription variants) on brain response to No and in relationship to trait anger reactivity and control. The orbitofrontal response did not differ as a function of the genotype. Instead, carriers of the low-MAOA genotype had reduced left middle frontal gyrus activation to No compared with the high variant. Furthermore, only for carriers of the up low-MAOA genotype, left amygdala and posterior thalamic activation to No increased with anger reactivity. Thus, vulnerability to aggression in carriers of the low-MAOA genotype is supported by decreased middle frontal response to No and the unique amygdala/thalamus association pattern in this group with anger reactivity but not anger control.

Neural Mechanisms of Anger Regulation as a Function of Genetic Risk for Violence

PubMed Central

Alia-Klein, Nelly; Goldstein, Rita Z.; Tomasi, Dardo; Woicik, Patricia A.; Moeller, Scott J.; Williams, Benjamin; Craig, Ian W.; Telang, Frank; Biegon, Anat; Wang, Gene-Jack; Fowler, Joanna S.; Volkow, Nora D.

2009-01-01

Genetic risk may predispose individuals to compromised anger regulation, potentially through modulation of brain responses to emotionally evocative stimuli. Emphatically expressed, the emotional word No can prohibit behavior through conditioning. In a recent functional magnetic resonance imaging study, the authors showed that healthy males attribute negative valence to No while showing a lateral orbitofrontal response that correlated with their self-reported anger control. Here, the authors examined the influence of the monoamine oxidase A (MAOA) gene (low vs. high transcription variants) on brain response to No and in relationship to trait anger reactivity and control. The orbitofrontal response did not differ as a function of the genotype. Instead, carriers of the low-MAOA genotype had reduced left middle frontal gyrus activation to No compared with the high variant. Furthermore, only for carriers of theup low-MAOA genotype, left amygdala and posterior thalamic activation to No increased with anger reactivity. Thus, vulnerability to aggression in carriers of the low-MAOA genotype is supported by decreased middle frontal response to No and the unique amygdala/thalamus association pattern in this group with anger reactivity but not anger control. PMID:19485616

Positive parenting predicts the development of adolescent brain structure: a longitudinal study.

PubMed

Whittle, Sarah; Simmons, Julian G; Dennison, Meg; Vijayakumar, Nandita; Schwartz, Orli; Yap, Marie B H; Sheeber, Lisa; Allen, Nicholas B

2014-04-01

Little work has been conducted that examines the effects of positive environmental experiences on brain development to date. The aim of this study was to prospectively investigate the effects of positive (warm and supportive) maternal behavior on structural brain development during adolescence, using longitudinal structural MRI. Participants were 188 (92 female) adolescents, who were part of a longitudinal adolescent development study that involved mother-adolescent interactions and MRI scans at approximately 12 years old, and follow-up MRI scans approximately 4 years later. FreeSurfer software was used to estimate the volume of limbic-striatal regions (amygdala, hippocampus, caudate, putamen, pallidum, and nucleus accumbens) and the thickness of prefrontal regions (anterior cingulate and orbitofrontal cortices) across both time points. Higher frequency of positive maternal behavior during the interactions predicted attenuated volumetric growth in the right amygdala, and accelerated cortical thinning in the right anterior cingulate (males only) and left and right orbitofrontal cortices, between baseline and follow up. These results have implications for understanding the biological mediators of risk and protective factors for mental disorders that have onset during adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Distinct Contributions of the Basolateral Amygdala and the Medial Prefrontal Cortex to Learning and Relearning Extinction of Context Conditioned Fear

ERIC Educational Resources Information Center

Laurent, Vincent; Westbrook, R. Frederick

2008-01-01

We studied the roles of the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in learning and relearning to inhibit context conditioned fear (freezing) in extinction. In Experiment 1, pre-extinction BLA infusion of the NMDA receptor (NMDAr) antagonist, ifenprodil, impaired the development and retention of inhibition but…

Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin-2A receptors.

PubMed

Gresch, P J; Strickland, L V; Sanders-Bush, E

2002-01-01

Lysergic acid diethylamide (LSD) produces altered mood and hallucinations in humans and binds with high affinity to serotonin-2A (5-HT(2A)) receptors. Although LSD interacts with other receptors, the activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic properties of LSD. The goal of this study was to identify the brain sites activated by LSD and to determine the influence of 5-HT(2A) receptors in this activation. Rats were pretreated with the 5-HT(2A) receptor antagonist MDL 100907 (0.3 mg/kg, i.p.) or vehicle 30 min prior to LSD (500 microg/kg, i.p.) administration and killed 3 h later. Brain tissue was examined for Fos protein expression by immunohistochemistry. LSD administration produced a five- to eight-fold increase in Fos-like immunoreactivity in medial prefrontal cortex, anterior cingulate cortex, and central nucleus of amygdala. However, in dorsal striatum and nucleus accumbens no increase in Fos-like immunoreactivity was observed. Pretreatment with MDL 100907 completely blocked LSD-induced Fos-like immunoreactivity in medial prefrontal cortex and anterior cingulate cortex, but only partially blocked LSD-induced Fos-like immunoreactivity in amygdala. Double-labeled immunohistochemistry revealed that LSD did not induce Fos-like immunoreactivity in cortical cells expressing 5-HT(2A) receptors, suggesting an indirect activation of cortical neurons. These results indicate that the LSD activation of medial prefrontal cortex and anterior cingulate cortex is mediated by 5-HT(2A) receptors, whereas in amygdala 5-HT(2A) receptor activation is a component of the response. These findings support the hypothesis that the medial prefrontal cortex, anterior cingulate cortex, and perhaps the amygdala, are important regions involved in the production of hallucinations. Copyright 2002 IBRO

Age-related changes in amygdala-frontal connectivity during emotional face processing from childhood into young adulthood.

PubMed

Wu, Minjie; Kujawa, Autumn; Lu, Lisa H; Fitzgerald, Daniel A; Klumpp, Heide; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

2016-05-01

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age-related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7-25 years. We found age-related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age-related change (shifting from positive to negative correlation) in amygdala-anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom-up amygdala excitatory signaling to ACC/mPFC in children and later development of top-down inhibitory control of ACC/mPFC over amygdala in adults. Age-related changes in amygdala-ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala-ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat-specific processing. Hum Brain Mapp 37:1684-1695, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Development of White Matter Microstructure and Intrinsic Functional Connectivity Between the Amygdala and Ventromedial Prefrontal Cortex: Associations With Anxiety and Depression.

PubMed

Jalbrzikowski, Maria; Larsen, Bart; Hallquist, Michael N; Foran, William; Calabro, Finnegan; Luna, Beatriz

2017-10-01

Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development. Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging. Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood. Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in the emergence of psychiatric disorders in adolescence. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effect of Different Forms of Hypokinesia on the Ultrastructure of Limbic, Extrapyramidal and Neocortical Areas of the Rat Brain: Electron Microscopic Study

NASA Astrophysics Data System (ADS)

Zhvania, Mzia G.; Japaridze, Nadezhda J.; Ksovreli, Mariam G.

The effect of chronic restraint stress and chronic hypokinesia "without stress" on the ultrastructure of central and lateral nuclei of amygdala, CA1 and CA3 area of the hippocampus, cingular cortex, nucleus caudatus and motor cortex of adult male rats were elucidated. In some neurons and synapses of abovementioned regions pathological modifications were revealed. More significant alterations provokes chronic restraint stress. Alterations are mostly concentrated: first—in the nuclei of amygdala, then in the CA1 and CA3 areas. Moderate alterations were observed in cingular cortex and nucleus caudatus. In comparing with it, hypokinesia "without stress" provokes only moderate modifications: predominantly in the nucleus caudatus, in lesser degree—in the hippocampus and amygdalae.

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.

Representation of economic preferences in the structure and function of the amygdala and prefrontal cortex

PubMed Central

Fermin, Alan S. R.; Sakagami, Masamichi; Kiyonari, Toko; Li, Yang; Matsumoto, Yoshie; Yamagishi, Toshio

2016-01-01

Social value orientations (SVOs) are economic preferences for the distribution of resources – prosocial individuals are more cooperative and egalitarian than are proselfs. Despite the social and economic implications of SVOs, no systematic studies have examined their neural correlates. We investigated the amygdala and dorsolateral prefrontal cortex (DLPFC) structures and functions in prosocials and proselfs by functional magnetic resonance imaging and evaluated cooperative behavior in the Prisoner’s Dilemma game. We found for the first time that amygdala volume was larger in prosocials and positively correlated with cooperation, while DLPFC volume was larger in proselfs and negatively correlated with cooperation. Proselfs’ decisions were marked by strong DLPFC and weak amygdala activity, and prosocials’ decisions were marked by strong amygdala activity, with the DLPFC signal increasing only in defection. Our findings suggest that proselfs’ decisions are controlled by DLPFC-mediated deliberative processes, while prosocials’ decisions are initially guided by automatic amygdala processes. PMID:26876988

Evidence for Shared Predisposition in the Relationship between Cannabis Use and Subcortical Brain Structure

PubMed Central

Pagliaccio, David; Barch, Deanna M.; Bogdan, Ryan; Wood, Phillip K.; Lynskey, Michael T.; Heath, Andrew C.; Agrawal, Arpana

2015-01-01

Importance Prior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use. Objective To determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations. Design Cross-sectional diagnostic interview, behavioral, and neuroimaging data. Setting Community sampling and established family registries. Participants Data from 483 participants (22-35 years old), enrolled in the on-going Human Connectome Project; 262 participants reported cannabis exposure, i.e. ever using cannabis in their lifetime. Main Outcome Measures Whole brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever use, age of onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed-models were used to examine volume differences in sex-matched, concordant unexposed (Npairs=71), exposed (Npairs=81), or exposure discordant (Npairs=89) sibling pairs. Results Cannabis exposure was related to smaller left amygdala (~2.3%) and right ventral striatum volumes (~3.5%). These volumetric differences were within the range of normal variation. The relationship between left amygdala volume and cannabis use was largely due to shared genetic factors (ρg=−0.43, p=0.004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use. Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs. Conclusions and Relevance Differences in amygdala volume in cannabis users are attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (e.g. ventral striatum) or at more severe levels of cannabis involvement and deserve further study. PMID:26308883

Aversive Learning Modulates Cortical Representations of Object Categories

PubMed Central

Dunsmoor, Joseph E.; Kragel, Philip A.; Martin, Alex; LaBar, Kevin S.

2014-01-01

Experimental studies of conditioned learning reveal activity changes in the amygdala and unimodal sensory cortex underlying fear acquisition to simple stimuli. However, real-world fears typically involve complex stimuli represented at the category level. A consequence of category-level representations of threat is that aversive experiences with particular category members may lead one to infer that related exemplars likewise pose a threat, despite variations in physical form. Here, we examined the effect of category-level representations of threat on human brain activation using 2 superordinate categories (animals and tools) as conditioned stimuli. Hemodynamic activity in the amygdala and category-selective cortex was modulated by the reinforcement contingency, leading to widespread fear of different exemplars from the reinforced category. Multivariate representational similarity analyses revealed that activity patterns in the amygdala and object-selective cortex were more similar among exemplars from the threat versus safe category. Learning to fear animate objects was additionally characterized by enhanced functional coupling between the amygdala and fusiform gyrus. Finally, hippocampal activity co-varied with object typicality and amygdala activation early during training. These findings provide novel evidence that aversive learning can modulate category-level representations of object concepts, thereby enabling individuals to express fear to a range of related stimuli. PMID:23709642

Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in Self-Control of Impulsive Desires.

PubMed

Krämer, Bernd; Gruber, Oliver

2015-01-01

Human decisions are guided by a variety of motivational factors, such as immediate rewards, long-term goals, and emotions. We used functional magnetic resonance imaging to investigate the dynamic functional interactions between the amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the influences of emotions, desires, and rationality on human decisions. We found that increased functional connectivity between the amygdala and the nucleus accumbens facilitated the approach of an immediate reward in the presence of emotional information. Further, increased functional interactions of the anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were associated with rational decisions in dilemma situations. These findings support previous animal studies by demonstrating that emotional signals from the amygdala and goal-oriented information from prefrontal cortices interface in the nucleus accumbens to guide human decisions and reward-directed actions. © 2015 S. Karger AG, Basel.

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

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.

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.

Shared neural coding for social hierarchy and reward value in primate amygdala.

PubMed

Munuera, Jérôme; Rigotti, Mattia; Salzman, C Daniel

2018-03-01

The social brain hypothesis posits that dedicated neural systems process social information. In support of this, neurophysiological data have shown that some brain regions are specialized for representing faces. It remains unknown, however, whether distinct anatomical substrates also represent more complex social variables, such as the hierarchical rank of individuals within a social group. Here we show that the primate amygdala encodes the hierarchical rank of individuals in the same neuronal ensembles that encode the rewards associated with nonsocial stimuli. By contrast, orbitofrontal and anterior cingulate cortices lack strong representations of hierarchical rank while still representing reward values. These results challenge the conventional view that dedicated neural systems process social information. Instead, information about hierarchical rank-which contributes to the assessment of the social value of individuals within a group-is linked in the amygdala to representations of rewards associated with nonsocial stimuli.

The amygdala and decision-making.

PubMed

Gupta, Rupa; Koscik, Timothy R; Bechara, Antoine; Tranel, Daniel

2011-03-01

Decision-making is a complex process that requires the orchestration of multiple neural systems. For example, decision-making is believed to involve areas of the brain involved in emotion (e.g., amygdala, ventromedial prefrontal cortex) and memory (e.g., hippocampus, dorsolateral prefrontal cortex). In this article, we will present findings related to the amygdala's role in decision-making, and differentiate the contributions of the amygdala from those of other structurally and functionally connected neural regions. Decades of research have shown that the amygdala is involved in associating a stimulus with its emotional value. This tradition has been extended in newer work, which has shown that the amygdala is especially important for decision-making, by triggering autonomic responses to emotional stimuli, including monetary reward and punishment. Patients with amygdala damage lack these autonomic responses to reward and punishment, and consequently, cannot utilize "somatic marker" type cues to guide future decision-making. Studies using laboratory decision-making tests have found deficient decision-making in patients with bilateral amygdala damage, which resembles their real-world difficulties with decision-making. Additionally, we have found evidence for an interaction between sex and laterality of amygdala functioning, such that unilateral damage to the right amygdala results in greater deficits in decision-making and social behavior in men, while left amygdala damage seems to be more detrimental for women. We have posited that the amygdala is part of an "impulsive," habit type system that triggers emotional responses to immediate outcomes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Resting-state functional connectivity of the amygdala in suicide attempters with major depressive disorder.

PubMed

Kang, Seung-Gul; Na, Kyoung-Sae; Choi, Jae-Won; Kim, Jeong-Hee; Son, Young-Don; Lee, Yu Jin

2017-07-03

In this study, we investigated the difference in resting-state functional connectivity (RSFC) of the amygdala between suicide attempters and non-suicide attempters with major depressive disorder (MDD) using functional magnetic resonance imaging (fMRI). This study included 19 suicide attempters with MDD and 19 non-suicide attempters with MDD. RSFC was compared between the two groups and the regression analyses were conducted to identify the correlation between RSFC and Scale for Suicide Ideation (SSI) scores in the suicide attempt group. Statistical significance was set at p-value (uncorrected) <0.005 with k≥28 voxels. Compared with non-suicide attempters, suicide attempters showed significantly increased RSFC of the left amygdala with the right insula and left superior orbitofrontal area, and increased RSFC of the right amygdala with the left middle temporal area. The regression analysis showed a significant correlation between the SSI total score and RSFC of the right amygdala with the right parahippocampal area in the suicide attempt group. The present RSFC findings provide evidence of a functional neural basis and will help reveal the pathophysiology underlying suicidality in subjects with MDD. Copyright © 2017. Published by Elsevier Inc.

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.

Trait and state patterns of basolateral amygdala connectivity at rest are related to endogenous testosterone and aggression in healthy young women.

PubMed

Buades-Rotger, Macià; Engelke, Christin; Krämer, Ulrike M

2018-05-09

The steroid hormone testosterone (T) has been suggested to influence reactive aggression upon its action on the basolateral amygdala (BLA), a key brain region for threat detection. However, it is unclear whether T modulates resting-state functional connectivity (rsFC) of the BLA, and whether this predicts subsequent aggressive behavior. Aggressive interactions themselves, which often induce changes in T concentrations, could further alter BLA rsFC, but this too remains untested. Here we investigated the effect of endogenous T on rsFC of the BLA at baseline as well as after an aggressive encounter, and whether this was related to behavioral aggression in healthy young women (n = 39). Pre-scan T was negatively correlated with basal rsFC between BLA and left superior temporal gyrus (STG; p < .001, p < .05 Family-Wise Error [FWE] cluster-level corrected), which in turn was associated with increased aggression (r = .37, p = .020). BLA-STG coupling at rest might thus underlie hostile readiness in low-T women. In addition, connectivity between the BLA and the right superior parietal lobule (SPL), a brain region involved in higher-order perceptual processes, was reduced in aggressive participants (p < .001, p < .05 FWE cluster-level corrected). On the other hand, post-task increases in rsFC between BLA and medial orbitofrontal cortex (mOFC) were linked to reduced aggression (r = -.36, p = .023), consistent with the established notion that the mOFC regulates amygdala activity in order to curb aggressive impulses. Finally, competition-induced changes in T were associated with increased coupling between the BLA and the right lateral OFC (p < .001, p < .05 FWE cluster-level corrected), but this effect was unrelated to aggression. We thus identified connectivity patterns that prospectively predict aggression in women, and showed how aggressive interactions in turn impact these neural systems.

NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

PubMed

Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

2018-05-26

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

Neural mechanisms associated with treatment decision making: An fMRI study.

PubMed

Abidi, Malek; Bruce, Jared; Le Blanche, Alain; Bruce, Amanda; Jarmolowicz, David P; Csillik, Antonia; Thai, N Jade; Lim, Seung-Lark; Heinzlef, Olivier; de Marco, Giovanni

2018-04-23

Great progress has been made in understanding how people make financial decisions. However, there is little research on how people make health and treatment choices. Our study aimed to examine how participants weigh benefits (reduction in disease progression) and probability of risk (medications' side effects) when making hypothetical treatment decisions, and to identify the neural networks implicated in this process. Fourteen healthy participants were recruited to perform a treatment decision probability discounting task using MRI. Behavioral responses and skin conductance responses (SCRs) were measured. A whole brain analysis were performed to compare activity changes between "mild" and "severe" medications' side effects conditions. Then, orbitofrontal cortex (OFC), ventral striatum (VS), amygdala and insula were chosen for effective connectivity analysis. Behavioral data showed that participants are more likely to refuse medication when side effects are high and efficacy is low. SCRs values were significantly higher when people made medication decisions in the severe compared to mild condition. Functionally, OFC and VS were activated in the mild condition and were associated with increased likehood of choosing to take medication (higher area under the curve "AUC" side effects/efficacy). These regions also demonstrated an increased effective connectivity when participants valued treatment benefits. By contrast, the OFC, insula and amygdala were activated in the severe condition and were associated with and increased likelihood to refuse treatment. These regions showed enhanced effective connectivity when participants were confronted with increased side effects severity. This is the first study to examine the behavioral and neural bases of medical decision making. Copyright © 2018 Elsevier B.V. All rights reserved.

Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.

PubMed

Feldstein Ewing, Sarah W; Claus, Eric D; Hudson, Karen A; Filbey, Francesca M; Yakes Jimenez, Elizabeth; Lisdahl, Krista M; Kong, Alberta S

2017-08-01

Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents' high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period.

Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury.

PubMed

Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A; Devanand, D P; Brickman, Adam M; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

2016-01-01

A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings.

GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity

PubMed Central

Pizzi, Stefano Delli; Chiacchieretta, Piero; Mantini, Dante; Bubbico, Giovanna; Edden, Richard A.; Onofrj, Marco; Ferretti, Antonio

2017-01-01

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top–down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions. PMID:28386778

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.

The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity

PubMed Central

Kraehenmann, Rainer; Schmidt, André; Friston, Karl; Preller, Katrin H.; Seifritz, Erich; Vollenweider, Franz X.

2015-01-01

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual–limbic–prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders. PMID:26909323

The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity.

PubMed

Kraehenmann, Rainer; Schmidt, André; Friston, Karl; Preller, Katrin H; Seifritz, Erich; Vollenweider, Franz X

2016-01-01

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual-limbic-prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.

Brain Metabolism during Hallucination-Like Auditory Stimulation in Schizophrenia

PubMed Central

Horga, Guillermo; Fernández-Egea, Emilio; Mané, Anna; Font, Mireia; Schatz, Kelly C.; Falcon, Carles; Lomeña, Francisco; Bernardo, Miguel; Parellada, Eduard

2014-01-01

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia. PMID:24416328

Computer-aided classification of Alzheimer's disease based on support vector machine with combination of cerebral image features in MRI

NASA Astrophysics Data System (ADS)

Jongkreangkrai, C.; Vichianin, Y.; Tocharoenchai, C.; Arimura, H.; Alzheimer's Disease Neuroimaging Initiative

2016-03-01

Several studies have differentiated Alzheimer's disease (AD) using cerebral image features derived from MR brain images. In this study, we were interested in combining hippocampus and amygdala volumes and entorhinal cortex thickness to improve the performance of AD differentiation. Thus, our objective was to investigate the useful features obtained from MRI for classification of AD patients using support vector machine (SVM). T1-weighted MR brain images of 100 AD patients and 100 normal subjects were processed using FreeSurfer software to measure hippocampus and amygdala volumes and entorhinal cortex thicknesses in both brain hemispheres. Relative volumes of hippocampus and amygdala were calculated to correct variation in individual head size. SVM was employed with five combinations of features (H: hippocampus relative volumes, A: amygdala relative volumes, E: entorhinal cortex thicknesses, HA: hippocampus and amygdala relative volumes and ALL: all features). Receiver operating characteristic (ROC) analysis was used to evaluate the method. AUC values of five combinations were 0.8575 (H), 0.8374 (A), 0.8422 (E), 0.8631 (HA) and 0.8906 (ALL). Although “ALL” provided the highest AUC, there were no statistically significant differences among them except for “A” feature. Our results showed that all suggested features may be feasible for computer-aided classification of AD patients.

Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task.

PubMed

Völlm, Birgit A; Taylor, Alexander N W; Richardson, Paul; Corcoran, Rhiannon; Stirling, John; McKie, Shane; Deakin, John F W; Elliott, Rebecca

2006-01-01

Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.

Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus.

PubMed

Schur, E A; Kleinhans, N M; Goldberg, J; Buchwald, D; Schwartz, M W; Maravilla, K

2009-06-01

To develop a non-invasive method of studying brain mechanisms involved in energy homeostasis and appetite regulation in humans by using visual food cues that are relevant to individuals attempting weight loss. Functional magnetic resonance imaging (fMRI) was used to compare brain activation in regions of interest between groups of food photographs. Ten healthy, non-obese women who were not dieting for weight loss. Independent raters viewed food photographs and evaluated whether the foods depicted should be eaten by individuals attempting a calorically-restricted diet. Based on their responses, we categorized photographs into 'non-fattening' and 'fattening' food groups, the latter characterized by high-caloric content and usually also high-fat or high-sugar content. Blood oxygen level-dependent (BOLD) response was measured by fMRI while participants viewed photographs of 'fattening' food, 'non-fattening' food, and non-food objects. Viewing photographs of fattening food compared with non-food objects resulted in significantly greater activation in the brainstem; hypothalamus; left amygdala; left dorsolateral prefrontal cortex; left orbitofrontal cortex; right insular cortex; bilateral striatum, including the nucleus accumbens, caudate nucleus, and putamen; bilateral thalamus; and occipital lobe. By comparison, only the occipital region had greater activation by non-fattening food than by object photographs. Combining responses to all food types resulted in attenuation of activation in the brainstem, hypothalamus, and striatum. These findings suggest that, in non-obese women, neural circuits engaged in energy homeostasis and reward processing are selectively attuned to representations of high-calorie foods that are perceived as fattening. Studies to investigate hormonal action or manipulation of energy balance may benefit from fMRI protocols that contrast energy-rich food stimuli with non-food or low-calorie food stimuli.

Sex differences in neural responses to stress and alcohol context cues.

PubMed

Seo, Dongju; Jia, Zhiru; Lacadie, Cheryl M; Tsou, Kristen A; Bergquist, Keri; Sinha, Rajita

2011-11-01

Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. This study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue, and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (P < 0.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum, and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the left dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala, and hippocampus than women, whereas women showed greater alcohol-cue-related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion-modulation regions, including the medial OFC, ventromedial PFC, left superior-mPFC, and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal, and ventral) in men, supporting its involvement in alcohol "urge" in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders. Copyright © 2010 Wiley-Liss, Inc.

Neural Correlates of Emotion Regulation in the Ventral Prefrontal Cortex and the Encoding of Subjective Value and Economic Utility

PubMed Central

Viviani, Roberto

2014-01-01

In many studies of the interaction between cognitive control and emotion, the orbitofrontal cortex/ventromedial prefrontal cortex (mOFC/vmPFC) has been associated with an inhibitory function on limbic areas activated by emotionally arousing stimuli, such as the amygdala. This has led to the hypothesis of an inhibitory or regulatory role of mOFC/vmPFC. In studies of cognition and executive function, however, this area is deactivated by focused effort, raising the issue of the nature of the putative regulatory process associated with mOFC/vmPFC. This issue is here revisited in light of findings in the neuroeconomics field demonstrating the importance of mOFC/vmPFC to encoding the subjective value of stimuli or their economic utility. Many studies show that mOFC/vmPFC activity may affect response by activating personal preferences, instead of resorting to effortful control mechanisms typically associated with emotion regulation. Based on these findings, I argue that a simple automatic/controlled dichotomy is insufficient to describe the data on emotion and control of response adequately. Instead, I argue that the notion of subjective value from neuroeconomics studies and the notion of attentional orienting may play key roles in integrating emotion and cognition. mOFC/vmPFC may work together with the inferior parietal lobe, the cortical region associated with attentional orienting, to convey information about motivational priorities and facilitate processing of inputs that are behaviorally relevant. I also suggest that the dominant mode of function of this ventral network may be a distinct type of process with intermediate properties between the automatic and the controlled, and which may co-operate with effortful control processes in order to steer response. PMID:25309459

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

Impact of Infralimbic Inputs on Intercalated Amygdale Neurons: A Biophysical Modeling Study

ERIC Educational Resources Information Center

Li, Guoshi; Amano, Taiju; Pare, Denis; Nair, Satish S.

2011-01-01

Intercalated (ITC) amygdala neurons regulate fear expression by controlling impulse traffic between the input (basolateral amygdala; BLA) and output (central nucleus; Ce) stations of the amygdala for conditioned fear responses. Previously, stimulation of the infralimbic (IL) cortex was found to reduce fear expression and the responsiveness of Ce…

Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex.

PubMed

Feng, Pan; Becker, Benjamin; Zheng, Yong; Feng, Tingyong

2018-02-01

Sleep plays an important role for successful fear memory consolidation. Growing evidence suggests that sleep disturbances might contribute to the development and the maintenance of posttraumatic stress disorder (PTSD), a disorders characterized by dysregulations in fear learning mechanisms, as well as exaggerated arousal and salience processing. Against this background, the present study examined the effects of sleep deprivation (SD) on the acquisition of fear and the subsequent neural consolidation. To this end, the present study assessed fear acquisition and associated changes in fMRI-based amygdala-functional connectivity following 24 h of SD. Relative to non-sleep deprived controls, SD subjects demonstrated increased fear ratings and skin conductance responses (SCR) during fear acquisition. During fear consolidation SD inhibited increased amygdala-ventromendial prefrontal cortex (vmPFC) connectivity and concomitantly increased changes in amygdala-insula connectivity. Importantly, whereas in controls fear indices during acquisition were negatively associated with amygdala-vmPFC connectivity during consolidation, fear indices were positively associated with amygdala-insula coupling following SD. Together the findings suggest that SD may interfere with vmPFC control of the amygdala and increase bottom-up arousal signaling in the amygdala-insula pathway during fear consolidation, which might mediate the negative impact of sleep disturbances on PSTD symptomatology.

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.

Reward and motivation systems: a brain mapping study of early-stage intense romantic love in Chinese participants.

PubMed

Xu, Xiaomeng; Aron, Arthur; Brown, Lucy; Cao, Guikang; Feng, Tingyong; Weng, Xuchu

2011-02-01

Early-stage romantic love has been studied previously in the United States and United Kingdom (Aron et al. [2005]: J Neurophysiol 94:327–337; Bartels and Zeki [2000]: Neuroreport 11:3829–3834; Ortigue et al. [2007]: J Cogn Neurosci 19:1218–1230), revealing activation in the reward and motivation systems of the brain. In this study, we asked what systems are activated for early-stage romantic love in Easterners, specifically Chinese participants? Are these activations affected by individual differences within a cultural context of Traditionality and Modernity? Also, are these brain activations correlated with later satisfaction in the relationship? In Beijing, we used the same procedure used by Aron et al. (Aron et al. [2005]: J Neurophysiol 94:327–337). The stimuli for 18 Chinese participants were a picture of the face of their beloved, the face of a familiar acquaintance, and a countback task. We found significant activations specific to the beloved in the reward and motivation systems, particularly, the ventral tegmental area and the caudate. The mid-orbitofrontal cortex and cerebellum were also activated, whereas amygdala, medial orbitofrontal, and medial accumbens activity were decreased relative to the familiar acquaintance. Self-reported Traditionality and Modernity scores were each positively correlated with activity in the nucleus accumbens, although in different regions and sides of the brain. Activity in the subgenual area and the superior frontal gyrus was associated with higher relationship happiness at 18-month follow-up. Our results show that midbrain dopamine-rich reward/motivation systems were activated by early-stage romantic love in Chinese participants, as found by other studies. Neural activity was associated with Traditionality and Modernity attitudes as well as with later relationship happiness for Chinese participants.

Bradycardia in frontotemporal dementia.

PubMed

Robles Bayón, A; Gude Sampedro, F; Torregrosa Quesada, J M

2014-03-01

Numerous regions of the brain, such as the medial frontal cortex, orbitofrontal cortex, insula, and amygdala, participate in the autonomic control of cardiovascular functions such as heart rate. The degenerative process in frontotemporal dementia (FTD) involves the listed anatomical structures and may therefore produce dysautonomic cardiovascular symptoms. To observe whether or not non-cardiogenic bradycardia was more frequent in a group of patients with FTD than in subjects with mild cognitive impairment or dementia of a different aetiology. Once patients with primary cardiac arrhythmia were excluded, we registered the heart rates of 258 patients with cognitive symptoms (36 with FTD, 22 with Alzheimer disease, 23 with vascular dementia, 10 with other dementias, and 167 with non-dementia cognitive impairment). Bradycardia (<60 beats/minute) was significantly more frequent in patients with FTD. This difference remained significant after excluding subjects undergoing treatment with a potentially bradycardic effect. Bradycardia was more prevalent in behavioural FTD cases than in cases of the aphasic variant, and we detected a trend toward higher frequency among patients with more pronounced right hemisphere atrophy. Moreover, mean systolic blood pressure in FTD patients was lower than in other participants, and systolic hypotension (<120 and <100mm Hg) was more prevalent. Bradycardia was more frequent in the FTD sample than in other patients with cognitive symptoms. Further investigations will be necessary before we may consider bradycardia to be a sign supporting diagnosis of FTD or its behavioural variant. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Empathy and aversion: the neural signature of mentalizing in Tourette syndrome.

PubMed

Eddy, C M; Cavanna, A E; Hansen, P C

2017-02-01

Previous studies suggest that adults with Tourette syndrome (TS) can respond unconventionally on tasks involving social cognition. We therefore hypothesized that these patients would exhibit different neural responses to healthy controls in response to emotionally salient expressions of human eyes. Twenty-five adults with TS and 25 matched healthy controls were scanned using fMRI during the standard version of the Reading the Mind in the Eyes Task which requires mental state judgements, and a novel comparison version requiring judgements about age. During prompted mental state recognition, greater activity was apparent in TS within left orbitofrontal cortex, posterior cingulate, right amygdala and right temporo-parietal junction (TPJ), while reduced activity was apparent in regions including left inferior parietal cortex. Age judgement elicited greater activity in TS within precuneus, medial prefrontal and temporal regions involved in mentalizing. The interaction between group and task revealed differential activity in areas including right inferior frontal gyrus. Task-related activity in the TPJ covaried with global ratings of the urge to tic. While recognizing mental states, adults with TS exhibit greater activity than controls in brain areas involved in the processing of negative emotion, in addition to reduced activity in regions associated with the attribution of agency. In addition, increased recruitment of areas involved in mental state reasoning is apparent in these patients when mentalizing is not a task requirement. Our findings highlight differential neural reactivity in response to emotive social cues in TS, which may interact with tic expression.

Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms

PubMed Central

Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

2014-01-01

Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic–striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences. PMID:24051900

Cumulative adversity sensitizes neural response to acute stress: association with health symptoms.

PubMed

Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

2014-02-01

Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic-striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences.

How mood challenges emotional memory formation: an fMRI investigation.

PubMed

Fitzgerald, Daniel A; Arnold, Jennifer F; Becker, Eni S; Speckens, Anne E M; Rinck, Mike; Rijpkema, Mark; Fernández, Guillén; Tendolkar, Indira

2011-06-01

Experimental mood manipulations and functional magnetic resonance imaging (fMRI) provide a unique opportunity for examining the neural correlates of mood-congruent memory formation. While prior studies in mood-disorder patients point to the medial temporal lobe in the genesis of mood-congruent memory (MCM) bias, the interaction between mood and emotional memory formation has not been investigated in healthy participants. In particular it remains unclear how regulatory structures in the pre-frontal cortex may be involved in mediating this phenomenon. In this study, event-related fMRI was performed on 20 healthy participants using a full-factorial, within-subjects repeated-measures design to examine how happy and sad moods impact memory for valenced stimuli (positive, negative and neutral words). Main effects of mood, stimulus valence and memory were examined as was activity related to successful memory formation during congruent and in-congruent moods. Behavioral results confirm an MCM bias while imaging results show amygdala and hippocampal engagement in a global mood and successful recall, respectively. MCM formation was characterized by increased activity during mood-congruent encoding of negative words in the orbito-frontal cortex (OFC) and for mood-incongruent processing of negative words in medial- and inferior-frontal gyri (MFG/IFG). These findings indicate that different pre-frontal regions facilitate mood-congruent and incongruent encoding of successfully recalled negative words at the time of learning, with OFC enhancing congruency and the left IFG and MFG helping overcome semantic incongruities between mood and stimulus valence. Copyright © 2011 Elsevier Inc. All rights reserved.

Being fed up: a social cognitive neuroscience approach to mental satiation.

PubMed

Mojzisch, Andreas; Schulz-Hardt, Stefan

2007-11-01

Being fed up with something is a prevalent and fundamental human experience. Although the relevance of mental satiation, that is, the process of becoming fed up with an action, is highly acknowledged in organizational psychology, almost no empirical research has examined this concept. In this article, we take a social cognitive neuroscience approach to mental satiation. By building on and extending the classic work of Lewin and Karsten, we propose a new model of mental satiation that focuses on the cognitive, motivational, and neural processes underlying mental satiation. Our model starts with the assumption that repeated performance of an action undermines one's need for competence and hence leads to a loss of intrinsic motivation. We then distinguish between two phases of the satiation process: The first phase is characterized by a loss of intrinsic motivation to perform the action. The second phase starts when the intrinsic motivation has vanished and volitional control is required to continue the action. We predict that the loss of intrinsic motivation in the first phase of the satiation process is correlated with a decrease in activity in brain regions associated with positive hedonic experience, such as the nucleus accumbens, the ventral pallidum, and the medial orbitofrontal cortex. In contrast, the growing aversion toward the action during the second phase of the satiation process is predicted to be correlated with an increase in activity in brain regions associated with unpleasant affect and volitional control, such as the amygdala, the anterior insula, and the anterior cingulate cortex.

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

Can Sophie's Choice Be Adequately Captured by Cold Computation of Minimizing Losses? An fMRI Study of Vital Loss Decisions

PubMed Central

Li, Qi; Qin, Shaozheng; Rao, Li-Lin; Zhang, Wencai; Ying, Xiaoping; Guo, Xiuyan; Guo, Chunyan; Ding, Jinghong; Li, Shu; Luo, Jing

2011-01-01

The vast majority of decision-making research is performed under the assumption of the value maximizing principle. This principle implies that when making decisions, individuals try to optimize outcomes on the basis of cold mathematical equations. However, decisions are emotion-laden rather than cool and analytic when they tap into life-threatening considerations. Using functional magnetic resonance imaging (fMRI), this study investigated the neural mechanisms underlying vital loss decisions. Participants were asked to make a forced choice between two losses across three conditions: both losses are trivial (trivial-trivial), both losses are vital (vital-vital), or one loss is trivial and the other is vital (vital-trivial). Our results revealed that the amygdala was more active and correlated positively with self-reported negative emotion associated with choice during vital-vital loss decisions, when compared to trivial-trivial loss decisions. The rostral anterior cingulate cortex was also more active and correlated positively with self-reported difficulty of choice during vital-vital loss decisions. Compared to the activity observed during trivial-trivial loss decisions, the orbitofrontal cortex and ventral striatum were more active and correlated positively with self-reported positive emotion of choice during vital-trivial loss decisions. Our findings suggest that vital loss decisions involve emotions and cannot be adequately captured by cold computation of minimizing losses. This research will shed light on how people make vital loss decisions. PMID:21412428

Neuroanatomical correlates of negative emotionality-related traits: A systematic review and meta-analysis.

PubMed

Mincic, Adina M

2015-10-01

Two central traits present in the most influential models of personality characterize the response to positive and, respectively, negative emotional events. Negative emotionality (NE)-related traits are linked to vulnerability to mood and anxiety disorders; this has fuelled a special interest in examining stable differences in brain morphology associated to these traits. Structural imaging methods including voxel-based morphometry, cortical thickness analysis and diffusion tensor imaging (DTI) have yielded inconclusive and sometimes contradictory results. This review summarizes the findings reported to date through these methods and discusses them in relation to the functional imaging results. To detect topographic convergence between studies showing positive and, respectively, negative grey matter associations with NE-traits, activation likelihood estimation (ALE) meta-analyses of VBM studies were performed. Individuals scoring high on NE-related traits show consistent morphological differences in a left-lateralized circuit: higher grey matter volume (GMV) in amygdala and anterior parahippocampal gyrus and lower GMV in the orbitofrontal cortex extending into perigenual anterior cingulate cortex. Most DTI studies indicate reduced white matter integrity in various brain regions and tracts, particularly in the uncinate fasciculus and in cingulum bundle. These results show that the behavioural phenotype associated to NE traits is reflected in structural differences within the cortico-limbic system, suggesting alterations in information processing and transmission. The results are discussed from the perspective of neuron-glia interactions. Future directions are outlined based on recent developments in structural imaging techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.

PubMed

Dellu-Hagedorn, Françoise; Rivalan, Marion; Fitoussi, Aurélie; De Deurwaerdère, Philippe

2018-04-19

Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons

PubMed Central

Maroun, Mouna; Ioannides, Pericles J.; Bergman, Krista L.; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L.

2013-01-01

Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. PMID:23714419

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.

Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory with Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

ERIC Educational Resources Information Center

Miranda, Maria I.; McGaugh, James L.

2004-01-01

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the…

Emotion, Cognition, and Mental State Representation in Amygdala and Prefrontal Cortex

PubMed Central

Salzman, C. Daniel; Fusi, Stefano

2011-01-01

Neuroscientists have often described cognition and emotion as separable processes implemented by different regions of the brain, such as the amygdala for emotion and the prefrontal cortex for cognition. In this framework, functional interactions between the amygdala and prefrontal cortex mediate emotional influences on cognitive processes such as decision-making, as well as the cognitive regulation of emotion. However, neurons in these structures often have entangled representations, whereby single neurons encode multiple cognitive and emotional variables. Here we review studies using anatomical, lesion, and neurophysiological approaches to investigate the representation and utilization of cognitive and emotional parameters. We propose that these mental state parameters are inextricably linked and represented in dynamic neural networks composed of interconnected prefrontal and limbic brain structures. Future theoretical and experimental work is required to understand how these mental state representations form and how shifts between mental states occur, a critical feature of adaptive cognitive and emotional behavior. PMID:20331363

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.

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

Sliding-window analysis tracks fluctuations in amygdala functional connectivity associated with physiological arousal and vigilance during fear conditioning.

PubMed

Baczkowski, Blazej M; Johnstone, Tom; Walter, Henrik; Erk, Susanne; Veer, Ilya M

2017-06-01

We evaluated whether sliding-window analysis can reveal functionally relevant brain network dynamics during a well-established fear conditioning paradigm. To this end, we tested if fMRI fluctuations in amygdala functional connectivity (FC) can be related to task-induced changes in physiological arousal and vigilance, as reflected in the skin conductance level (SCL). Thirty-two healthy individuals participated in the study. For the sliding-window analysis we used windows that were shifted by one volume at a time. Amygdala FC was calculated for each of these windows. Simultaneously acquired SCL time series were averaged over time frames that corresponded to the sliding-window FC analysis, which were subsequently regressed against the whole-brain seed-based amygdala sliding-window FC using the GLM. Surrogate time series were generated to test whether connectivity dynamics could have occurred by chance. In addition, results were contrasted against static amygdala FC and sliding-window FC of the primary visual cortex, which was chosen as a control seed, while a physio-physiological interaction (PPI) was performed as cross-validation. During periods of increased SCL, the left amygdala became more strongly coupled with the bilateral insula and anterior cingulate cortex, core areas of the salience network. The sliding-window analysis yielded a connectivity pattern that was unlikely to have occurred by chance, was spatially distinct from static amygdala FC and from sliding-window FC of the primary visual cortex, but was highly comparable to that of the PPI analysis. We conclude that sliding-window analysis can reveal functionally relevant fluctuations in connectivity in the context of an externally cued task. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural circuitry of emotional face processing in autism spectrum disorders.

PubMed

Monk, Christopher S; Weng, Shih-Jen; Wiggins, Jillian Lee; Kurapati, Nikhil; Louro, Hugo M C; Carrasco, Melisa; Maslowsky, Julie; Risi, Susan; Lord, Catherine

2010-03-01

Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. The small sample size may have affected our ability to detect additional group differences. When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.

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.

Effects of emotional valence and arousal on the voice perception network

PubMed Central

Kotz, Sonja A.; Belin, Pascal

2017-01-01

Abstract Several theories conceptualise emotions along two main dimensions: valence (a continuum from negative to positive) and arousal (a continuum that varies from low to high). These dimensions are typically treated as independent in many neuroimaging experiments, yet recent behavioural findings suggest that they are actually interdependent. This result has impact on neuroimaging design, analysis and theoretical development. We were interested in determining the extent of this interdependence both behaviourally and neuroanatomically, as well as teasing apart any activation that is specific to each dimension. While we found extensive overlap in activation for each dimension in traditional emotion areas (bilateral insulae, orbitofrontal cortex, amygdalae), we also found activation specific to each dimension with characteristic relationships between modulations of these dimensions and BOLD signal change. Increases in arousal ratings were related to increased activations predominantly in voice-sensitive cortices after variance explained by valence had been removed. In contrast, emotions of extreme valence were related to increased activations in bilateral voice-sensitive cortices, hippocampi, anterior and midcingulum and medial orbito- and superior frontal regions after variance explained by arousal had been accounted for. Our results therefore do not support a complete segregation of brain structures underpinning the processing of affective dimensions. PMID:28449127

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.

Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear

PubMed Central

Rodriguez-Romaguera, Jose; Do Monte, Fabricio H. M.; Quirk, Gregory J.

2012-01-01

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD. PMID:22586125

Own-gender imitation activates the brain's reward circuitry

PubMed Central

Iacoboni, Macro; Martin, Alia; Dapretto, Mirella

2012-01-01

Imitation is an important component of human social learning throughout life. Theoretical models and empirical data from anthropology and psychology suggest that people tend to imitate self-similar individuals, and that such imitation biases increase the adaptive value (e.g., self-relevance) of learned information. It is unclear, however, what neural mechanisms underlie people's tendency to imitate those similar to themselves. We focused on the own-gender imitation bias, a pervasive bias thought to be important for gender identity development. While undergoing fMRI, participants imitated own- and other-gender actors performing novel, meaningless hand signs; as control conditions, they also simply observed such actions and viewed still portraits of the same actors. Only the ventral and dorsal striatum, orbitofrontal cortex and amygdala were more active when imitating own- compared to other-gender individuals. A Bayesian analysis of the BrainMap neuroimaging database demonstrated that the striatal region preferentially activated by own-gender imitation is selectively activated by classical reward tasks in the literature. Taken together, these findings reveal a neurobiological mechanism associated with the own-gender imitation bias and demonstrate a novel role of reward-processing neural structures in social behavior. PMID:22383803

Insensitive parenting may accelerate the development of the amygdala-medial prefrontal cortex circuit.

PubMed

Thijssen, Sandra; Muetzel, Ryan L; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Tiemeier, Henning; Verhulst, Frank C; White, Tonya; Van Ijzendoorn, Marinus H

2017-05-01

This study examined whether the association between age and amygdala-medial prefrontal cortex (mPFC) connectivity in typically developing 6- to 10-year-old children is correlated with parental care. Resting-state functional magnetic resonance imaging scans were acquired from 124 children of the Generation R Study who at 4 years old had been observed interacting with their parents to assess maternal and paternal sensitivity. Amygdala functional connectivity was assessed using a general linear model with the amygdalae time series as explanatory variables. Higher level analyses assessing Sensitivity × Age as well as exploratory Sensitivity × Age × Gender interaction effects were performed restricted to voxels in the mPFC. We found significant Sensitivity × Age interaction effects on amygdala-mPFC connectivity. Age was related to stronger amygdala-mPFC connectivity in children with a lower combined parental sensitivity score (b = 0.11, p = .004, b = 0.06, p = .06, right and left amygdala, respectively), but not in children with a higher parental sensitivity score, (b = -0.07, p = .12, b = -0.06, p = .12, right and left amygdala, respectively). A similar effect was found for maternal sensitivity, with stronger amygdala-mPFC connectivity in children with less sensitive mothers. Exploratory (parental, maternal, paternal) Sensitivity × Age × Gender interaction analyses suggested that this effect was especially pronounced in girls. Amygdala-mPFC resting-state functional connectivity has been shown to increase from age 10.5 years onward, implying that the positive association between age and amygdala-mPFC connectivity in 6- to 10-year-old children of less sensitive parents represents accelerated development of the amygdala-mPFC circuit.

[Is emotional dysregulation a component of attention-deficit/hyperactivity disorder (ADHD)?].

PubMed

Villemonteix, T; Purper-Ouakil, D; Romo, L

2015-04-01

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents. It is characterized by age-inappropriate inattention/impulsiveness and/or hyperactivity symptoms. ADHD shows a high comorbidity with oppositional defiant disorder (ODD), a disorder that features symptoms of emotional lability. Due to this comorbidity, emotional lability was long considered a secondary consequence of ADHD, which could arise under the influence of environmental factors such as inefficient parenting practices, as part of an ODD diagnosis. In this model of heterotypic continuity, emotional lability was considered not to play any causal role regarding ADHD symptomatology. As opposed to this view, it is now well established that a large number of children with ADHD and without any comorbid disorder exhibit symptoms of emotional lability. Furthermore, recent studies have found that negative emotionality accounts for significant unique variance in ADHD symptom severity, along with motor-perceptual and executive function deficits. Barkley proposed that ADHD is characterized by deficits of executive functions, and that a deficiency in the executive control of emotions is a necessary component of ADHD. According to this theory, the extent to which an individual with ADHD displays a deficiency in behavioral inhibition is the extent to which he or she will automatically display an equivalent degree of deficiency in emotional inhibition. However, not all children with ADHD exhibit symptoms of emotional lability, and studies have found that the association between emotional lability and ADHD was not mediated by executive function or motivational deficits. Task-based and resting state neuroimaging studies have disclosed an altered effective connectivity between regions dedicated to emotional regulation in children with ADHD when compared to typically developing children, notably between the amygdala, the prefrontal cortex, the hippocampus and the ventral striatum. Morphological alterations of the amygdala have also been reported in previous structural studies in children with ADHD. Emotional lability can result from different neurobiological mechanisms. In particular, bottom-up and top-down processes can be opposed. Bottom-up related emotional dysregulation involves an increased emotional reactivity, and is thought to be linked to the automatic evaluative activity of the amygdala. Top-down mechanisms are associated with the regulation of such activity, and rely on a prefrontal network including the lateral prefrontal cortex, the anterior cingulate cortex and the orbitofrontal cortex. Since various neuropsychological impairments and alterations in multiple brain networks have been implicated in the etiology of ADHD, contemporary models emphasize its neuropsychological heterogeneity. It is therefore likely that some but not all children with ADHD will exhibit neurobiological alterations in circuits dedicated to emotional regulation, possibly at different levels. Future research will have to identify the different causal pathways and to decide whether emotional lability represents a criterion to subtype ADHD diagnoses. Emotional dysregulation is now known to play a causal role regarding ADHD symptomatology. Along with executive functioning, reaction time variability and potentially delay aversion, emotional dysregulation should therefore be included in future theoretical models of ADHD, as well as in clinical practice when identifying the major impairments in this diagnostic group and when deciding therapeutic strategies. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Threatening faces induce fear circuitry hypersynchrony in soldiers with post-traumatic stress disorder.

PubMed

Dunkley, Benjamin T; Pang, Elizabeth W; Sedge, Paul A; Jetly, Rakesh; Doesburg, Sam M; Taylor, Margot J

2016-01-01

Post-traumatic stress disorder (PTSD) is associated with atypical responses to emotional face stimuli with preferential processing given to threat-related facial expressions via hyperactive amygdalae disengaged from medial prefrontal modulation. We examined implicit emotional face perception in soldiers with (n = 20) and without (n = 25) PTSD using magnetoencephalography to define spatiotemporal network interactions, and a subsequent region-of-interest analysis to characterize the network role of the right amygdala and medial prefrontal cortex in threatening face perception. Contrasts of network interactions revealed the PTSD group were hyperconnected compared to controls in the phase-locking response in the 2-24 Hz range for angry faces, but not for happy faces when contrasting groups. Hyperconnectivity in PTSD was greatest in the posterior cingulate, right ventromedial prefrontal cortex, right parietal regions and the right temporal pole, as well as the right amygdala. Graph measures of right amygdala and medial prefrontal connectivity revealed increases in node strength and clustering in PTSD, but not inter-node connectivity. Additionally, these measures were found to correlate with anxiety and depression. In line with prior studies, amygdala hyperconnectivity was observed in PTSD in relation to threatening faces, but the medial prefrontal cortex also displayed enhanced connectivity in our network-based approach. Overall, these results support preferential neurophysiological encoding of threat-related facial expressions in those with PTSD.

Extinguishing trace fear engages the retrosplenial cortex rather than the amygdala

PubMed Central

Kwapis, Janine L.; Jarome, Timothy J.; Lee, Jonathan L.; Gilmartin, Marieke R.; Helmstetter, Fred J.

2013-01-01

Extinction learning underlies the treatment for a variety of anxiety disorders. Most of what is known about the neurobiology of extinction is based on standard “delay” fear conditioning, in which awareness is not required for learning. Little is known about how complex, explicit associations extinguish, however. “Trace” conditioning is considered to be a rodent model of explicit fear because it relies on both the cortex and hippocampus and requires explicit contingency awareness in humans. Here, we explore the neural circuit supporting trace fear extinction in order to better understand how complex memories extinguish. We first show that the amygdala is selectively involved in delay fear extinction; blocking intra-amygdala glutamate receptors disrupted delay, but not trace extinction. Further, ERK phosphorylation was increased in the amygdala after delay, but not trace extinction. We then identify the retrosplenial cortex (RSC) as a key structure supporting trace extinction. ERK phosphorylation was selectively increased in the RSC following trace extinction and blocking intra-RSC NMDA receptors impaired trace, but not delay extinction. These findings indicate that delay and trace extinction require different neural circuits; delay extinction requires plasticity in the amygdala whereas trace extinction requires the RSC. Anxiety disorders linked to explicit memory may therefore depend on cortical processes that have not been traditionally targeted by extinction studies based on delay fear. PMID:24055593

The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder.

PubMed

Velasquez, Francisco; Wiggins, Jillian Lee; Mattson, Whitney I; Martin, Donna M; Lord, Catherine; Monk, Christopher S

2017-04-01

Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Distinct brain activity in processing negative pictures of animals and objects --- the role of human contexts

PubMed Central

Cao, Zhijun; Zhao, Yanbing; Tan, Tengteng; Chen, Gang; Ning, Xueling; Zhan, Lexia; Yang, Jiongjiong

2013-01-01

Previous studies have shown that the amygdala is important in processing not only animate entities but also social information. It remains to be determined to what extent the factors of category and social context interact to modulate the activities of the amygdala and cortical regions. In this study, pictures depicting animals and inanimate objects in negative and neutral levels were presented. The contexts of the pictures differed in whether they included human/human parts. The factors of valence, arousal, familiarity and complexity of pictures were controlled across categories. The results showed that the amygdala activity was modulated by category and contextual information. Under the nonhuman context condition, the amygdala responded more to animals than objects for both negative and neutral pictures. In contrast, under the human context condition, the amygdala showed stronger activity for negative objects than animals. In addition to cortical regions related to object action, functional and effective connectivity analyses showed that the anterior prefrontal cortex interacted with the amygdala more for negative objects (vs. animals) in the human context condition, by a top-down modulation of the anterior prefrontal cortex to the amygdala. These results highlighted the effects of category and human contexts on modulating brain activity in emotional processing. PMID:24099847

Smaller amygdala volume and reduced anterior cingulate gray matter density associated with history of post-traumatic stress disorder.

PubMed

Rogers, Mark A; Yamasue, Hidenori; Abe, Osamu; Yamada, Haruyasu; Ohtani, Toshiyuki; Iwanami, Akira; Aoki, Shigeki; Kato, Nobumasa; Kasai, Kiyoto

2009-12-30

Although post-traumatic stress disorder (PTSD) may be seen to represent a failure to extinguish learned fear, significant aspects of the pathophysiology relevant to this hypothesis remain unknown. Both the amygdala and hippocampus are necessary for fear extinction occur, and thus both regions may be abnormal in PTSD. Twenty-five people who experienced the Tokyo subway sarin attack in 1995, nine who later developed PTSD and 16 who did not, underwent magnetic resonance imaging (MRI) with manual tracing to determine bilateral amygdala and hippocampus volumes. At the time of scanning, one had PTSD and eight had a history of PTSD. Results indicated that the group with a history of PTSD had significantly smaller mean bilateral amygdala volume than did the group that did not develop PTSD. Furthermore, left amygdala volume showed a significant negative correlation with severity of PTSD symptomatology as well as reduced gray matter density in the left anterior cingulate cortex. To our knowledge, this is the first observation of an association between PTSD and amygdala volume. Furthermore the apparent interplay between amygdala and anterior cingulate cortex represents support at the level of gross brain morphology for the theory of PTSD as a failure of fear extinction.

Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons.

PubMed

Maroun, Mouna; Ioannides, Pericles J; Bergman, Krista L; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L

2013-08-01

Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

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

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

Salicylate-induced cochlear impairments, cortical hyperactivity and re-tuning, and tinnitus.

PubMed

Chen, Guang-Di; Stolzberg, Daniel; Lobarinas, Edward; Sun, Wei; Ding, Dalian; Salvi, Richard

2013-01-01

High doses of sodium salicylate (SS) have long been known to induce temporary hearing loss and tinnitus, effects attributed to cochlear dysfunction. However, our recent publications reviewed here show that SS can induce profound, permanent, and unexpected changes in the cochlea and central nervous system. Prolonged treatment with SS permanently decreased the cochlear compound action potential (CAP) amplitude in vivo. In vitro, high dose SS resulted in a permanent loss of spiral ganglion neurons and nerve fibers, but did not damage hair cells. Acute treatment with high-dose SS produced a frequency-dependent decrease in the amplitude of distortion product otoacoustic emissions and CAP. Losses were greatest at low and high frequencies, but least at the mid-frequencies (10-20 kHz), the mid-frequency band that corresponds to the tinnitus pitch measured behaviorally. In the auditory cortex, medial geniculate body and amygdala, high-dose SS enhanced sound-evoked neural responses at high stimulus levels, but it suppressed activity at low intensities and elevated response threshold. When SS was applied directly to the auditory cortex or amygdala, it only enhanced sound evoked activity, but did not elevate response threshold. Current source density analysis revealed enhanced current flow into the supragranular layer of auditory cortex following systemic SS treatment. Systemic SS treatment also altered tuning in auditory cortex and amygdala; low frequency and high frequency multiunit clusters up-shifted or down-shifted their characteristic frequency into the 10-20 kHz range thereby altering auditory cortex tonotopy and enhancing neural activity at mid-frequencies corresponding to the tinnitus pitch. These results suggest that SS-induced hyperactivity in auditory cortex originates in the central nervous system, that the amygdala potentiates these effects and that the SS-induced tonotopic shifts in auditory cortex, the putative neural correlate of tinnitus, arises from the interaction between the frequency-dependent losses in the cochlea and hyperactivity in the central nervous system. Copyright © 2012 Elsevier B.V. All rights reserved.

Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals.

PubMed

Frijling, Jessie L; van Zuiden, Mirjam; Koch, Saskia B J; Nawijn, Laura; Veltman, Dick J; Olff, Miranda

2016-04-01

Approximately 10% of trauma-exposed individuals go on to develop post-traumatic stress disorder (PTSD). Neural emotion regulation may be etiologically involved in PTSD development. Oxytocin administration early post-trauma may be a promising avenue for PTSD prevention, as intranasal oxytocin has previously been found to affect emotion regulation networks in healthy individuals and psychiatric patients. In a randomized double-blind placebo-controlled between-subjects functional magnetic resonance (fMRI) study, we assessed the effects of a single intranasal oxytocin administration (40 IU) on seed-based amygdala resting-state FC with emotion regulation areas (ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC)), and salience processing areas (insula, dorsal anterior cingulate cortex (dACC)) in 37 individuals within 11 days post trauma. Two resting-state scans were acquired; one after neutral- and one after trauma-script-driven imagery. We found that oxytocin administration reduced amygdala-left vlPFC FC after trauma script-driven imagery, compared with neutral script-driven imagery, whereas in PL-treated participants enhanced amygdala-left vlPFC FC was observed following trauma script-driven imagery. Irrespective of script condition, oxytocin increased amygdala-insula FC and decreased amygdala-vmPFC FC. These neural effects were accompanied by lower levels of sleepiness and higher flashback intensity in the oxytocin group after the trauma script. Together, our findings show that oxytocin administration may impede emotion regulation network functioning in response to trauma reminders in recently trauma-exposed individuals. Therefore, caution may be warranted in administering oxytocin to prevent PTSD in distressed, recently trauma-exposed individuals.

Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression.

PubMed

Connolly, Colm G; Ho, Tiffany C; Blom, Eva Henje; LeWinn, Kaja Z; Sacchet, Matthew D; Tymofiyeva, Olga; Simmons, Alan N; Yang, Tony T

2017-01-01

The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents. We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24). Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later. Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized. Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time. Copyright © 2016 Elsevier B.V. All rights reserved.

Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats.

PubMed

Maeng, Lisa Y; Cover, Kara K; Taha, Mohamad B; Landau, Aaron J; Milad, Mohammed R; Lebrón-Milad, Kelimer

2017-01-02

There is growing evidence that estradiol (E2) enhances fear extinction memory consolidation. However, it is unclear how E2 influences the nodes of the fear extinction network to enhance extinction memory. This study begins to delineate the neural circuits underlying the influence of E2 on fear extinction acquisition and consolidation in female rats. After fear conditioning (day 1), naturally cycling female rats underwent extinction learning (day 2) in a low-E2 state, receiving a systemic administration of either E2 or vehicle prior to extinction training. Extinction memory recall was then tested 24 hr later (day 3). We measured immediate early gene c-fos expression within the extinction network during fear extinction learning and extinction recall. During extinction learning, E2 treatment increased centrolateral amygdala c-fos activity and reduced lateral amygdala activity relative to vehicle. During extinction recall, E2-treated rats exhibited reduced c-fos expression in the centromedial amygdala. There were no group differences in c-fos expression within the medial prefrontal cortex or dorsal hippocampus. Examining c-fos ratios with the infralimbic cortex (IL) revealed that, despite the lack of group differences within the IL, E2 treatment induced greater IL activity relative to both prelimbic cortex and central amygdala (CeA) activity during extinction memory recall. Only the relationship between IL and CeA activity positively correlated with extinction retention. In conclusion, E2 appears to modify interactions between the IL and the CeA in females, shifting from stronger amygdalar modulation of fear during extinction learning to stronger IL control during extinction recall. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed

Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

2011-09-01

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

Altered Amygdala Resting-State Functional Connectivity in Maintenance Hemodialysis End-Stage Renal Disease Patients with Depressive Mood.

PubMed

Chen, Hui Juan; Wang, Yun Fei; Qi, Rongfeng; Schoepf, U Joseph; Varga-Szemes, Akos; Ball, B Devon; Zhang, Zhe; Kong, Xiang; Wen, Jiqiu; Li, Xue; Lu, Guang Ming; Zhang, Long Jiang

2017-04-01

The purpose of this study was to investigate patterns in the amygdala-based emotional processing circuit of hemodialysis patients using resting-state functional MR imaging (rs-fMRI). Fifty hemodialysis patients (25 with depressed mood and 25 without depressed mood) and 26 healthy controls were included. All subjects underwent neuropsychological tests and rs-fMRI, and patients also underwent laboratory tests. Functional connectivity of the bilateral amygdala was compared among the three groups. The relationship between functional connectivity and clinical markers was investigated. Depressed patients showed increased positive functional connectivity of the left amygdala with the left superior temporal gyrus and right parahippocampal gyrus (PHG) but decreased amygdala functional connectivity with the left precuneus, angular gyrus, posterior cingulate cortex (PCC), and left inferior parietal lobule compared with non-depressed patients (P < 0.05, AlphaSim corrected). Depressed patients had increased positive functional connectivity of the right amygdala with bilateral supplementary motor areas and PHG but decreased amygdala functional connectivity with the right superior frontal gyrus, superior parietal lobule, bilateral precuneus, and PCC (P < 0.05, AlphaSim corrected). After including anxiety as a covariate, we discovered additional decreased functional connectivity with anterior cingulate cortex (ACC) for bilateral amygdala (P < 0.05, AlphaSim corrected). For the depressed, neuropsychological test scores were correlated with functional connectivity of multiple regions (P < 0.05, AlphaSim corrected). In conclusion, functional connectivity in the amygdala-prefrontal-PCC-limbic circuits was impaired in depressive hemodialysis patients, with a gradual decrease in ACC between controls, non-depressed, and depressed patients for the right amygdala. This indicates that ACC plays a role in amygdala-based emotional regulatory circuits in these patients.

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.

Dissociated emergent-response system and fine-processing system in human neural network and a heuristic neural architecture for autonomous humanoid robots.

PubMed

Yan, Xiaodan

2010-01-01

The current study investigated the functional connectivity of the primary sensory system with resting state fMRI and applied such knowledge into the design of the neural architecture of autonomous humanoid robots. Correlation and Granger causality analyses were utilized to reveal the functional connectivity patterns. Dissociation was within the primary sensory system, in that the olfactory cortex and the somatosensory cortex were strongly connected to the amygdala whereas the visual cortex and the auditory cortex were strongly connected with the frontal cortex. The posterior cingulate cortex (PCC) and the anterior cingulate cortex (ACC) were found to maintain constant communication with the primary sensory system, the frontal cortex, and the amygdala. Such neural architecture inspired the design of dissociated emergent-response system and fine-processing system in autonomous humanoid robots, with separate processing units and another consolidation center to coordinate the two systems. Such design can help autonomous robots to detect and respond quickly to danger, so as to maintain their sustainability and independence.

The "proactive" model of learning: Integrative framework for model-free and model-based reinforcement learning utilizing the associative learning-based proactive brain concept.

PubMed

Zsuga, Judit; Biro, Klara; Papp, Csaba; Tajti, Gabor; Gesztelyi, Rudolf

2016-02-01

Reinforcement learning (RL) is a powerful concept underlying forms of associative learning governed by the use of a scalar reward signal, with learning taking place if expectations are violated. RL may be assessed using model-based and model-free approaches. Model-based reinforcement learning involves the amygdala, the hippocampus, and the orbitofrontal cortex (OFC). The model-free system involves the pedunculopontine-tegmental nucleus (PPTgN), the ventral tegmental area (VTA) and the ventral striatum (VS). Based on the functional connectivity of VS, model-free and model based RL systems center on the VS that by integrating model-free signals (received as reward prediction error) and model-based reward related input computes value. Using the concept of reinforcement learning agent we propose that the VS serves as the value function component of the RL agent. Regarding the model utilized for model-based computations we turned to the proactive brain concept, which offers an ubiquitous function for the default network based on its great functional overlap with contextual associative areas. Hence, by means of the default network the brain continuously organizes its environment into context frames enabling the formulation of analogy-based association that are turned into predictions of what to expect. The OFC integrates reward-related information into context frames upon computing reward expectation by compiling stimulus-reward and context-reward information offered by the amygdala and hippocampus, respectively. Furthermore we suggest that the integration of model-based expectations regarding reward into the value signal is further supported by the efferent of the OFC that reach structures canonical for model-free learning (e.g., the PPTgN, VTA, and VS). (c) 2016 APA, all rights reserved).

Visual attention modulates brain activation to angry voices.

PubMed

Mothes-Lasch, Martin; Mentzel, Hans-Joachim; Miltner, Wolfgang H R; Straube, Thomas

2011-06-29

In accordance with influential models proposing prioritized processing of threat, previous studies have shown automatic brain responses to angry prosody in the amygdala and the auditory cortex under auditory distraction conditions. However, it is unknown whether the automatic processing of angry prosody is also observed during cross-modal distraction. The current fMRI study investigated brain responses to angry versus neutral prosodic stimuli during visual distraction. During scanning, participants were exposed to angry or neutral prosodic stimuli while visual symbols were displayed simultaneously. By means of task requirements, participants either attended to the voices or to the visual stimuli. While the auditory task revealed pronounced activation in the auditory cortex and amygdala to angry versus neutral prosody, this effect was absent during the visual task. Thus, our results show a limitation of the automaticity of the activation of the amygdala and auditory cortex to angry prosody. The activation of these areas to threat-related voices depends on modality-specific attention.

Unseen fearful faces promote amygdala guidance of attention.

PubMed

Troiani, Vanessa; Price, Elinora T; Schultz, Robert T

2014-02-01

Little is known about the network of brain regions activated prior to explicit awareness of emotionally salient social stimuli. We investigated this in a functional magnetic resonance imaging study using a technique that combined elements of binocular rivalry and motion flash suppression in order to prevent awareness of fearful faces and houses. We found increased left amygdala and fusiform gyrus activation for fearful faces compared to houses, despite suppression from awareness. Psychophysiological interaction analyses showed that amygdala activation was associated with task-specific (fearful faces greater than houses) modulation of an attention network, including bilateral pulvinar, bilateral insula, left frontal eye fields, left intraparietal sulcus and early visual cortex. Furthermore, we report an unexpected main effect of increased left parietal cortex activation associated with suppressed fearful faces compared to suppressed houses. This parietal finding is the first report of increased dorsal stream activation for a social object despite suppression, which suggests that information can reach parietal cortex for a class of emotionally salient social objects, even in the absence of awareness.

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.

Pubertal testosterone influences threat-related amygdala–orbitofrontal cortex coupling

PubMed Central

Forbes, Erika E.; Ladouceur, Cecile D.; Worthman, Carol M.; Olino, Thomas M.; Ryan, Neal D.; Dahl, Ronald E.

2015-01-01

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala–orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala–OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed. PMID:24795438

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.

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

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

PubMed

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Beyond arousal and valence: the importance of the biological versus social relevance of emotional stimuli.

PubMed

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-03-01

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images' subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.

Beyond arousal and valence: The importance of the biological versus social relevance of emotional stimuli

PubMed Central

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-01-01

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention; memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that: a) biologically emotional images hold attention more strongly than socially emotional images, b) memory for biologically emotional images was enhanced even with limited cognitive resources, but c) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in visual cortex and greater functional connectivity between amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between amygdala and MPFC than biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity. PMID:21964552

Visual hallucinations are associated with hyperconnectivity between the amygdala and visual cortex in people with a diagnosis of schizophrenia.

PubMed

Ford, Judith M; Palzes, Vanessa A; Roach, Brian J; Potkin, Steven G; van Erp, Theo G M; Turner, Jessica A; Mueller, Bryon A; Calhoun, Vincent D; Voyvodic, Jim; Belger, Aysenil; Bustillo, Juan; Vaidya, Jatin G; Preda, Adrian; McEwen, Sarah C; Mathalon, Daniel H

2015-01-01

While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Visual Hallucinations Are Associated With Hyperconnectivity Between the Amygdala and Visual Cortex in People With a Diagnosis of Schizophrenia

PubMed Central

Ford, Judith M.; Palzes, Vanessa A.; Roach, Brian J.; Potkin, Steven G.; van Erp, Theo G. M.; Turner, Jessica A.; Mueller, Bryon A.; Calhoun, Vincent D.; Voyvodic, Jim; Belger, Aysenil; Bustillo, Juan; Vaidya, Jatin G.; Preda, Adrian; McEwen, Sarah C.; Mathalon, Daniel H.

2015-01-01

Introduction: While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. Methods: We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). Results: Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. Conclusions: VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia. PMID:24619536

Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

PubMed Central

Motomura, Yuki; Kitamura, Shingo; Nakazaki, Kyoko; Oba, Kentaro; Katsunuma, Ruri; Terasawa, Yuri; Hida, Akiko; Moriguchi, Yoshiya; Mishima, Kazuo

2017-01-01

Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD)]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL) evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD). Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF) and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC), and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life. PMID:28713328

Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.

PubMed

Wei, Luqing; Chen, Hong; Wu, Guo-Rong

2018-01-01

The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.

Neurobiological mechanisms underlying the blocking effect in aversive learning.

PubMed

Eippert, Falk; Gamer, Matthias; Büchel, Christian

2012-09-19

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

Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing.

PubMed

Delli Pizzi, Stefano; Chiacchiaretta, Piero; Mantini, Dante; Bubbico, Giovanna; Ferretti, Antonio; Edden, Richard A; Di Giulio, Camillo; Onofrj, Marco; Bonanni, Laura

2017-04-01

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala-mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala-mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1 H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion.