Connectivity Of Ventral Striatum Research Articles

Changed ventral striatum structural covariance and grey matter volume in depression during a one-year follow-up

Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD.

Striatal Functional Alterations Link to Distinct Symptomatology Across Mood States in Bipolar Disorder

BackgroundAs a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. MethodsBehavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. ResultsPatients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores. ConclusionsOur data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.

Neurocomputational Substrates Underlying the Effect of Identifiability on Third-Party Punishment.

The identifiable target effect refers to the preference for helping identified victims and punishing identifiable perpetrators compared with equivalent but unidentifiable counterparts. The identifiable target effect is often attributed to the heightened moral emotions evoked by identified targets. However, the specific neurocognitive processes that mediate and/or modulate this effect remain largely unknown. Here, we combined a third-party punishment game with brain imaging and computational modeling to unravel the neurocomputational underpinnings of the identifiable transgressor effect. Human participants (males and females) acted as bystanders and punished identified or anonymous wrongdoers. Participants were more punitive toward identified wrongdoers than anonymous wrongdoers because they took a vicarious perspective of victims and adopted lower reference points of inequity (i.e., more stringent norms) in the identified context than in the unidentified context. Accordingly, there were larger activity of the ventral anterior insula, more distinct multivariate neural patterns in the dorsal anterior insula and dorsal anterior cingulate cortex, and lower strength between ventral anterior insula and dorsolateral PFC and between dorsal anterior insula and ventral striatum connectivity in response to identified transgressors than anonymous transgressors. These findings implicate the interplay of expectancy violations, emotions, and self-interest in the identifiability effect. Last, individual differences in the identifiability effect were associated with empathic concern/social dominance orientation, activity in the precuneus/cuneus and temporo-parietal junction, and intrinsic functional connectivity of the dorsolateral PFC. Together, our work is the first to uncover the neurocomputational processes mediating identifiable transgressor effect and to characterize psychophysiological profiles modulating the effect.SIGNIFICANCE STATEMENT The identifiable target effect, more help to identified victims or stronger punishment to identifiable perpetrators, is common in daily life. We examined the neurocomputational mechanisms mediating/modulating the identifiability effect on third-party punishment by bridging literature from economics and cognitive neuroscience. Our findings reveal that identifiable transgressor effect is mediated by lower reference points of inequity (i.e., more stringent norms), which might be associated with a stronger involvement of the emotion processes and a weaker engagement of the analytic/deliberate processes. Furthermore, personality traits, altered brain activity, and intrinsic functional connectivity contribute to the individual variance in the identifiability effect. Overall, our study advances the understanding of the identifiability effect by shedding light on its component processes and modulating factors.

Irritability in early to middle childhood: Cross-sectional and longitudinal associations with resting state amygdala and ventral striatum connectivity

BackgroundIrritability is a common symptom that may affect children’s brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4–8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time. MethodsTypically developing children, ages 4–8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a “younger” cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an “older” cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions. ResultsCross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort. ConclusionsFindings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.

Longitudinal Trajectory of the Link Between Ventral Striatum and Depression in Adolescence.

Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium. iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivityrw). The main analyses assessed associations of VS connectivityrw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations. Higher right VS connectivityrw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivityrw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivityrw and anhedonia emerged in the structural equation model: left VS connectivityrw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivityrw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivityrw did not predict low mood at any time point in the structural equation model. The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivityrw in anhedonia but not in low mood.

Manipulating Reward Sensitivity Using Reward Circuit–Targeted Transcranial Magnetic Stimulation

BackgroundThe reward circuit is important for motivation and learning, and dysregulations of the reward circuit are prominent in anhedonic depression. Noninvasive interventions that can selectively target the reward circuit may hold promise for the treatment of anhedonia. MethodsWe tested a novel transcranial magnetic stimulation intervention for modulating the reward circuit. A total of 35 healthy individuals participated in a crossover controlled study targeting the reward circuit or a control site with intermittent theta burst stimulation (iTBS), an excitatory form of transcranial magnetic stimulation. Individual reward circuit targets were defined based upon functional magnetic resonance imaging functional connectivity with the ventral striatum, yielding targets in the rostromedial prefrontal cortex (rmPFC). Reward circuit function was assessed at baseline using functional magnetic resonance imaging, and reward circuit modulation was assessed using an event-related potential referred to as the reward positivity, which has been shown to reliably track reward sensitivity, as well as individual differences in depression and risk for depression. ResultsRelative to control iTBS, rmPFC iTBS enhanced the reward positivity. This effect was moderated by reward function, suggesting greater enhancements in individuals with lower reward function. This effect was also moderated by rmPFC–ventral striatum connectivity insofar as iTBS reached the rmPFC, suggesting that efficacy relies jointly on the strength of the rmPFC–ventral striatum pathway and ability of transcranial magnetic stimulation to target the rmPFC. ConclusionsThese data suggest that the reward circuit can be modulated by rmPFC iTBS, and amenability to such modulations is related to measures of reward circuit function. This provides the first step toward a novel noninvasive treatment of disorders of the reward circuit.

Frontostriatal functional connectivity underlies self-enhancement during social evaluation.

Self-enhancement, the tendency to view oneself positively, is a pervasive social motive widely investigated in the psychological sciences. Relatively little is known about the neurocognitive mechanisms underlying this motive, specifically in social-evaluative situations. To investigate whether positive emotion regulation circuitry, circuitry involved in modulating positive affect, relates to the self-enhancement motive in social contexts, we conducted an functional magnetic resonance imaging (fMRI) study in a healthy young adult sample. We hypothesized that self-enhancement indices (state and trait self-esteem) would relate to greater functional connectivity between right ventrolateral prefrontal cortex (RVLPFC), a region implicated in emotion regulation, and the ventral striatum (VS), a region associated with reward-related affect, during a social feedback task. Following social evaluation, participants experienced stable or decreased state self-esteem. Results showed that stable state self-esteem from pre- to post-scan and higher trait self-esteem related to greater RVLPFC–VS connectivity during positive evaluation. Stable-state self-esteem also related to greater RVLPFC–VS connectivity during negative evaluation. Moreover, RVLPFC activation during all types of feedback processing and left VS activation during negative feedback processing was greater for participants with stable-state self-esteem. These findings implicate neurocognitive mechanisms underlying emotion regulation in the self-enhancement motive and highlight a pathway through which self-enhancement may restore feelings of self-worth during threatening situations.

Neural mechanisms of reward processing in adolescent irritability.

Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent irritability and reward-related brain function as a candidate neural mechanism. Adolescents from intervention-seeking families in the community (N=52; mean age=13.80, SD=1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole-brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to irritability. Irritability was measured using the parent- and youth-reported Affective Reactivity Index. Irritability was associated with altered reward processing-related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex-mediated top-down control may be related to irritability. These findings inform our understanding of the etiology of youth irritability and the development of mechanism-based interventions.

Reward-related neural correlates in adolescents with excess body weight

The functional and connectivity reward processing in adults with excessive body weight is well documented, though is relatively less researched during adolescence. Given that reward and inhibition may be highly malleable during adolescence, it is unknown how impulsive behaviors, potentially stemming from impaired inhibitory control and heightened sensitivity to rewarding cues, relate to increases in body weight in adolescents. Adolescents (N = 76; mean age = 14.10 years, SD = 1.92) with varied body mass index (BMI) performed a child-friendly monetary incentive delay task during functional magnetic resonance imaging, to study reward processing during the anticipation of rewards (cue) and reactions to feedback about rewards (feedback). Our results show that adolescents with greater BMI z-score show neural activation and ventral striatum connectivity alterations in networks implicated in reward, salience detection, and inhibitory control. These bottom-up reward and top-down inhibitory control networks, as well as interactions between these networks were prevalent during the anticipation period (when the cue is presented) as well as when receiving feedback about whether one has received a reward. Specifically, our results were mainly driven by failure to receive a reward in the feedback period, and the anticipation of a potential reward in the anticipation period. Overall, we provide evidence for heightened reward salience as well as inhibitory control deficits that, in combination, may contribute to the impulsive behaviors that lead to higher BMI in adolescents.

The Neural Processes Interlinking Social Isolation, Social Support, and Problem Alcohol Use.

BackgroundSubjective feeling of social isolation, as can be measured by perceived burdensomeness (PB), is a major risk factor for alcohol misuse. Heightened PB is associated with elevated stress response and diminished cognitive control, both of which contribute to problem drinking. Here, we sought to identify the neural substrates underlying the relationship between PB and alcohol misuse.MethodsWe employed resting-state functional magnetic resonance imaging data collected from 61 problem drinkers to characterize the functional connectivity of the hypothalamus and ventral striatum (VS) in relation to PB. We specifically examined whether the connectivities of the hypothalamus and VS were differentially influenced by PB to produce contrasting effects on alcohol use. Finally, we evaluated how individual differences in social support modulate the inter-relationships of social isolation, neural connectivity, and the severity of problem drinking.ResultsWhole-brain multiple regressions show a positive relationship between PB and hypothalamic connectivity with the hippocampus and an inverse pattern for VS connectivity with the middle frontal gyrus. Difference in strength between the 2 connectivities predicted the severity of problem drinking, suggesting an imbalance involving elevated hypothalamic and diminished prefrontal cortical modulation in socially isolated problem drinkers. A path analysis further revealed that the lack of social support was associated with a bias toward low prefrontal connectivity, which in turn increased PB and facilitated problem drinking.ConclusionsAltered hypothalamus and VS connectivity may underlie problem drinking induced by social isolation. The current findings also highlight the important role of social support as a potential protective factor against alcohol misuse.

Cluster analysis with MOODS-SR illustrates a potential bipolar disorder risk phenotype in young adults with remitted major depressive disorder.

Delays in the diagnosis and detection of bipolar disorder can lead to adverse consequences, including improper treatment and increased suicide risk. The Mood Spectrum Self-Report Measure (MOODS-SR) was designed to capture the full spectrum of lifetime mood symptomology with factor scores for depression and mania symptom constellations. The utility of the MOODS-SR as a tool to investigate homogeneous subgroups was examined, with particular focus on a possible bipolar risk subgroup. Moreover, potential patterns of differences in MOODS-SR subtypes were probed using cognitive vulnerabilities, neuropsychological functioning, and ventral striatum connectivity. K-mean cluster analysis based on factor scores of MOODS-SR was used to determine homogeneous subgroupings within a healthy and remitted depressed young adult sample (N = 86). Between-group comparisons (based on cluster subgroupings) were conducted on measures of cognitive vulnerabilities, neuropsychological functioning, and ventral striatum rs-fMRI connectivity. Three groups of participants were identified: one with minimal symptomology, one with moderate primarily depressive symptomology, and one with more severe manic and depressive symptomology. Differences in impulsivity, neuroticism, conscientiousness, facial perception accuracy, and rs-fMRI connectivity exist between moderate and severe groups. Within a sample of people with and without depression histories, a severe subgroup was identified with potentially increased risk of developing bipolar disorder through use of the MOODS-SR. This small subgroup had higher levels of lifetime depression and mania symptoms. Additionally, differences in traits, affective processing, and connectivity exist between those with a more prototypic unipolar subgrouping and those with potential risk for developing bipolar disorder.

Affective traits and history of depression are related to ventral striatum connectivity

IntroductionStudying remitted Major Depressive Disorder (rMDD) facilitates a better understanding of neural mechanisms for risk, given that confounding effects of active symptoms are removed. Disrupted functional connectivity has been reported in multiple networks in MDD. However, no study to date of rMDD has specifically examined connectivity of the ventral striatum (VS), a region highly implicated in reward and motivation. We investigated functional connectivity of the VS in individuals with and without a history of MDD, and in relation to affective personality traits. MethodsForty-two individuals with rMDD and 28 healthy controls across two sites completed resting-state fMRI and the Behavioral Inhibition System/Behavioral Activation System Scale. Voxel-wise, whole-brain comparisons were conducted across and between groups for four seeds: left and right inferior VS (VSi), left and right superior VS (VSs). ResultsVSs connectivity to temporal and subcortical regions including the putamen and amygdala was positive and greater in HCs compared to rMDD individuals. Across groups, VSi connectivity was positively correlated with trait reward-responsiveness in somatomotor regions. Across groups, VSs connectivity was positively correlated with trait drive, particularly in the putamen, parahippocampal, and inferior temporal gyrus, and was negatively associated with trait behavioral inhibition in the anterior cingulate, frontal gyri, and insula. LimitationsLimitations include scanning at two sites and using multiple comparisons. DiscussionGroup connectivity differences emerged from the VSs rather than VSi. VSs showed associations with trait drive and behavioral inhibition, whereas VSi corrrelated with reward-responsiveness. Depression history and affective traits contribute meaningful and specific information about VS connectivity in understanding risk for MDD.

Hemispheric lateralization of resting-state functional connectivity of the ventral striatum: an exploratory study

Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The ventral striatum (VS) is critical to motivated behavior, with extant studies suggesting functional hemispheric asymmetry. The current work investigated differences in rsFC between the left (L) and right (R) VS and explored gender differences in the extent of functional lateralization. In 106 adults, we computed a laterality index (fcLI) to query whether a target region shows greater or less connectivity to the L vs R VS. A total of 45 target regions with hemispheric masks were examined from the Automated Anatomic Labeling atlas. One-sample t test was performed to explore significant laterality in the whole sample and in men and women separately. Two-sample t test was performed to examine gender differences in fcLI. At a corrected threshold (p < 0.05/45 = 0.0011), the dorsomedial prefrontal cortex (dmPFC) and posterior cingulate cortex (pCC) showed L lateralization and the intraparietal sulcus (IPS) and supramarginal gyrus (SMG) showed R lateralization in VS connectivity. Except for the pCC, these findings were replicated in a different data set (n = 97) from the Human Connectome Project. Furthermore, the fcLI of VS-pCC was negatively correlated with a novelty seeking trait in women but not in men. Together, the findings may suggest a more important role of the L VS in linking saliency response to self control and other internally directed processes. Right lateralization of VS connectivity to the SMG and IPS may support attention and action directed to external behavioral contingencies.

LATENT SUBSTRATES OF COMPULSIVITY AND BEHAVIOURAL FLEXIBILITY

Parallel decisional systems constantly compete for control of our day-to-day choices. Recent computational models propose two distinct forms of reinforcement learning, model-based and model free, which drive goal-directed and habitual behaviours, respectively. Although most of us seem to effortlessly alternate between the two systems, several pathological disorders have been associated with their imbalance. Thus the need to further characterize such systems is clear.To examine the neural networks of these parallel processes, we employ a two-step sequential learning task used previously to show simultaneous engagement of model-based and model-free learning in healthy volunteers [1] and their imbalance in pathological states [2]. We separately acquired fMRI data from 66 healthy volunteers during rest using a novel multi-echo planar sequence that greatly boosts signal-to-noise ratios compared to traditional single-echo sequences thus allowing higher spatial resolution of subcortical structures [3]. We quantified the connectivity between regions of interest (ROI’s) by calculating Pearson correlations coefficients (R) between a priori hypothesized regions (henceforth referred to as ‘connectivity’). These connectivity values were then correlated with behavioural measures. Higher model-based learning was positively correlated with medial orbitofrontal cortex and ventral striatum connectivity (R=0.32, p=0.01). Model-based scores also positively correlated with connectivity between dorsolateral prefrontal cortex and ventral striatum (R=0.27, p=0.03). In contrast, model-free learning was positively correlated with posterior putamen and supplementary motor area connectivity (R=0.266, p=0.033); and negatively with medial orbitofrontal cortex and left amygdala connectivity (R=-0.255, p=0.042). Model-free learning was also positively correlated with right ventral striatum and amygdala connectivity (R=0.274, p=0.028). We finally show that cognitive flexibility in the form of attention set shifting is associated with functional connectivity between dorsolateral prefrontal cortex and ventral striatum (R=-0.298, p=0.021).These findings suggest a neural network for model-based learning involving: integration of instrumental performance (ventral striatum); flexible, computationally-driven updating of outcome value based on changing internal motivational states and external feedback (medial orbitofrontal cortex); and computation of the relative advantage of alternative action values (dorsolateral prefrontal cortex). The current findings provide a more integrative network model of how previously implicated cortical regions organize to drive goal-directed model-based learning. Whereas most previous findings have focused on the neural correlates of model-based learning, we highlight a motoric frontal-striatal network associated with model-free learning. Together, we illustrate the sensitivity of the multi-echo sequence for the distinguishment of such elusive behavioural control systems.

Ventral Striatum Connectivity During Reward Anticipation in Adolescent Smokers

ABSTRACTSubstance misusers, including adolescent smokers, often have reduced reward system activity during processing of non-drug rewards. Using a psychophysiological interaction approach, we examined functional connectivity with the ventral striatum during reward anticipation in a large (N = 206) sample of adolescent smokers. Increased smoking frequency was associated with (1) increased connectivity with regions involved in saliency and valuation, including the orbitofrontal cortex and (2) reduced connectivity between the ventral striatum and regions associated with inhibition and risk aversion, including the right inferior frontal gyrus. These results demonstrate that functional connectivity during reward processing is relevant to adolescent addiction.

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

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).

Winning is not enough: ventral striatum connectivity during physical aggression.

Social neuroscience studies have shown that the ventral striatum (VS), a highly reward-sensitive brain area, is activated when participants win competitive tasks. However, in these settings winning often entails both avoiding punishment and punishing the opponent. It is thus unclear whether the rewarding properties of winning are mainly associated to punishment avoidance, or if punishing the opponent can be additionally gratifying. In the present paper we explored the neurophysiological correlates of each outcome, aiming to better understand the development of aggression episodes. We previously introduced a competitive reaction time task that separates both effects: in half of the won trials, participants can physically punish their opponent (active trials), whereas in the other half they can only avoid a punishment (passive trials). We performed functional connectivity analysis seeded in the VS to test for differential network interactions in active compared to passive trials. The VS showed greater connectivity with areas involved in reward valuation (orbitofrontal cortex), arousal (dorsal thalamus and posterior insula), attention (inferior occipital gyrus), and motor control (supplementary motor area) in active compared to passive trials, whereas connectivity between the VS and the inferior frontal gyrus decreased. Interindividual variability in connectivity strength between VS and posterior insula was related to aggressive behavior, whereas connectivity between VS and supplementary motor area was related to faster reaction times in active trials. Our results suggest that punishing a provoking opponent when winning might adaptively favor a "competitive state" in the course of an aggressive interaction.

Effect of relevance on amygdala activation and association with the ventral striatum

While the amygdala historically has been implicated in emotional stimuli processing, recent data suggest a general role in parceling out the relevance of stimuli, regardless of their emotional properties. Using functional magnetic resonance imaging, we tested the relevance hypothesis by investigating human amygdala responses to emotionally neutral stimuli while manipulating their relevance. The task was operationalized as highly relevant if a subsequent opportunity to respond for a reward depended on response accuracy of the task, and less relevant if the reward opportunity was independent of task performance. A region of interest analysis revealed bilateral amygdala activations in response to the high relevance condition compared to the low relevance condition. An exploratory whole-brain analysis yielded robust similar results in bilateral ventral striatum. A subsequent functional connectivity analysis demonstrated increased connectivity between amygdala and ventral striatum for the highly relevant stimuli compared to the less relevant stimuli. These findings suggest that the amygdala's processing profile goes beyond detection of emotions per se, and directly support the proposed role in relevance detection. In addition, the findings suggest a close relationship between amygdala and ventral striatal activity when processing relevant stimuli. Thus, the results may indicate that human amygdala modulates ventral striatum activity and subsequent behaviors beyond that observed for emotional cues, to encompass a broader range of relevant stimuli.

Opposing amygdala and ventral striatum connectivity during emotion identification

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 anticorrelation 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.

Striatal functional connectivity networks are modulated by fMRI resting state conditions

Resting state fluctuations in blood oxygenation level dependent functional connectivity magnetic resonance imaging (BOLD fcMRI) time-series have been increasingly employed to study functional connectivity networks in healthy and diseased brain. FcMRI studies have been conducted under a number of different conditions, including resting eyes open, visual fixation and finger tapping. BOLD fcMRI networks are believed to reflect both anatomically constrained spontaneous fluctuations and state-dependent activity. In this study, state-dependence of functional connectivity to dorsal and ventral striatum was assessed with fcMRI during an eyes open resting state condition (REST) and during continuous 3Hz transcutaneous electrical nerve stimulation (TENS), with the a priori hypotheses: (1) dorsal striatum connectivity with sensorimotor/attention networks will be stronger during TENS compared to REST, (2) ventral striatum connectivity with limbic system emotion-processing network will be weaker during TENS compared to REST and (3) ventral striatum connectivity with sensorimotor/attention networks will be stronger during TENS compared to REST. These hypotheses were confirmed by the results obtained, indicating that resting state BOLD fMRI networks reflect, in substantial measure, state-dependent activity.