Neural correlates of intonation and lexical tone in tonal and non‐tonal language speakers

Intonation, the modulation of pitch in speech, is a crucial aspect of language that is processed in right‐hemispheric regions, beyond the classical left‐hemispheric language system. Whether or not this notion generalises across languages remains, however, unclear. Particularly, tonal languages are an interesting test case because of the dual linguistic function of pitch that conveys lexical meaning in form of tone, in addition to intonation. To date, only few studies have explored how intonation is processed in tonal languages, how this compares to tone and between tonal and non‐tonal language speakers. The present fMRI study addressed these questions by testing Mandarin and German speakers with Mandarin material. Both groups categorised mono‐syllabic Mandarin words in terms of intonation, tone, and voice gender. Systematic comparisons of brain activity of the two groups between the three tasks showed large cross‐linguistic commonalities in the neural processing of intonation in left fronto‐parietal, right frontal, and bilateral cingulo‐opercular regions. These areas are associated with general phonological, specific prosodic, and controlled categorical decision‐making processes, respectively. Tone processing overlapped with intonation processing in left fronto‐parietal areas, in both groups, but evoked additional activity in bilateral temporo‐parietal semantic regions and subcortical areas in Mandarin speakers only. Together, these findings confirm cross‐linguistic commonalities in the neural implementation of intonation processing but dissociations for semantic processing of tone only in tonal language speakers.     

Reward‐related regions form a preferentially coupled system at rest

Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting‐state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal‐directed tasks. Here we use seed‐based and graph‐theory RSFC approaches to characterize the systems‐level organization of putative reward regions of at rest. Peaks of connectivity from seed‐based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph‐theory was then used to determine system‐level membership for all regions. Several regions previously implicated in reward‐processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta‐analyses of task‐based reward studies. This reward system shares between‐system connectivity with systems implicated in cognitive control and self‐regulation, including the fronto‐parietal, cingulo‐opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo‐opercular and default systems, OFC regions show stronger connectivity with the fronto‐parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self‐regulation failure, and addiction.     

Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD

The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task‐based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age‐matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task‐based activation patterns. Traditional univariate case‐control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo‐parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto‐limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo‐parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task‐based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD. Hum Brain Mapp 35:3083–3094, 2014. © 2013 Wiley Periodicals, Inc.     

Fronto‐temporal connectivity predicts cognitive empathy deficits and experiential negative symptoms in schizophrenia

Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting‐state functional connectivity between data‐driven networks, or components (referred to as, inter‐component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1 : We examined associations between cognitive empathy and medial prefrontal and temporal inter‐component connectivity at rest using a group‐matched schizophrenia and control sample. We then assessed whether inter‐component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2 : We sought to replicate the connectivity‐symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter‐component connectivity, a medial‐fronto‐temporal metric and an orbito‐fronto‐temporal metric were related to cognitive empathy. Moreover, the medial‐fronto‐temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111–1124, 2017. © 2016 Wiley Periodicals, Inc.     

Synchronization in the prefrontal–striatal circuit tracks behavioural choice in a go–no‐go task in rats

Rodent striatum is involved in sensory‐motor transformations and reward‐related learning. Lesion studies suggest dorsolateral striatum, dorsomedial striatum and nucleus accumbens underlie stimulus–response transformations, goal‐directed behaviour and reward expectation, respectively. In addition, prefrontal inputs likely control these functions. Here, we set out to study how reward‐driven behaviour is mediated by the coordinated activity of these structures in the intact brain. We implemented a discrimination task requiring rats to either respond or suppress responding on a lever after the presentation of auditory cues in order to obtain rewards. Single unit activity in the striatal subregions and pre‐limbic cortex was recorded using tetrode arrays. Striatal units showed strong onset responses to auditory cues paired with an opportunity to obtain reward. Cue‐onset responses in both striatum and cortex were significantly modulated by previous errors suggesting a role of these structures in maintaining appropriate motivation or action selection during ongoing behaviour. Furthermore, failure to respond to the reward‐paired tones was associated with higher pre‐trial coherence among striatal subregions and between cortex and striatum suggesting a task‐negative corticostriatal network whose activity may be suppressed to enable processing of reward‐predictive cues. Our findings highlight that coordinated activity in a distributed network including both pre‐limbic cortex and multiple striatal regions underlies reward‐related decisions.     

Mindfulness meditation regulates anterior insula activity during empathy for social pain

Mindfulness has been shown to reduce stress, promote health, and well‐being, as well as to increase compassionate behavior toward others. It reduces distress to one's own painful experiences, going along with altered neural responses, by enhancing self‐regulatory processes and decreasing emotional reactivity. In order to investigate if mindfulness similarly reduces distress and neural activations associated with empathy for others' socially painful experiences, which might in the following more strongly motivate prosocial behavior, the present study compared trait, and state effects of long‐term mindfulness meditation (LTM) practice. To do so we acquired behavioral data and neural activity measures using functional magnetic resonance imaging (fMRI) during an empathy for social pain task while manipulating the meditation state between two groups of LTM practitioners that were matched with a control group. The results show increased activations of the anterior insula (AI) and anterior cingulate cortex (ACC) as well as the medial prefrontal cortex and temporal pole when sharing others' social suffering, both in LTM practitioners and controls. However, in LTM practitioners, who practiced mindfulness meditation just prior to observing others' social pain, left AI activation was lower and the strength of AI activation following the mindfulness meditation was negatively associated with trait compassion in LTM practitioners. The findings suggest that current mindfulness meditation could provide an adaptive mechanism in coping with distress due to the empathic sharing of others' suffering, thereby possibly enabling compassionate behavior. Hum Brain Mapp 38:4034–4046, 2017. © 2017 Wiley Periodicals, Inc.     

Predicting vocal emotion expressions from the human brain

Speech is an important carrier of emotional information. However, little is known about how different vocal emotion expressions are recognized in a receiver's brain. We used multivariate pattern analysis of functional magnetic resonance imaging data to investigate to which degree distinct vocal emotion expressions are represented in the receiver's local brain activity patterns. Specific vocal emotion expressions are encoded in a right fronto‐operculo‐temporal network involving temporal regions known to subserve suprasegmental acoustic processes and a fronto‐opercular region known to support emotional evaluation, and, moreover, in left temporo‐cerebellar regions covering sequential processes. The right inferior frontal region, in particular, was found to differentiate distinct emotional expressions. The present analysis reveals vocal emotion to be encoded in a shared cortical network reflected by distinct brain activity patterns. These results shed new light on theoretical and empirical controversies about the perception of distinct vocal emotion expressions at the level of large‐scale human brain signals. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Right-ear precedence and vocal emotion contagion: The role of the left hemisphere

Much evidence suggests that the processing of emotions is lateralized to the right hemisphere of the brain. However, under some circumstances the left hemisphere might play a role, particularly for positive emotions and emotional experiences. We explored whether emotion contagion was right-lateralized, lateralized valence-specifically, or potentially left-lateralized. In two experiments, right-handed female listeners rated to what extent emotionally intoned pseudo-sentences evoked target emotions in them. These sound stimuli had a 7?ms ear lead in the left or right channel, leading to stronger stimulation of the contralateral hemisphere. In both experiments, the results revealed that right ear lead stimuli received subtly but significantly higher evocation scores, suggesting a left hemisphere dominance for emotion contagion. A control experiment using an emotion identification task showed no effect of ear lead. The findings are discussed in relation to prior findings that have linked the processing of emotional prosody to left-hemisphere brain regions that regulate emotions, control orofacial musculature, are involved in affective empathy processing areas, or have an affinity for processing emotions socially. Future work is needed to eliminate alternative interpretations and understand the mechanisms involved. Our novel binaural asynchrony method may be useful in future work in auditory laterality.     

Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

Nusslock R, Almeida JRC, Forbes EE, Versace A, Frank E, LaBarbara EJ, Klein CR, Phillips ML. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disord 2012: 14: 249–260. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar disorder may be characterized by a hypersensitivity to reward‐relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward‐processing and approach‐related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods: Twenty‐one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card‐guessing paradigm designed to examine reward‐related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results: Region‐of‐interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right‐sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward relative to healthy controls (p < 0.05, corrected). Whole‐brain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left‐lateral OFC (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions: Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward‐relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward‐related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness.     

Reward anticipation in the adolescent and aging brain

Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U‐shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J‐shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition‐related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan‐related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age‐specific effects in fronto‐parietal regions. Hum Brain Mapp 35:5153–5165, 2014. © 2014 Wiley Periodicals, Inc .     

The accumbofrontal tract: Diffusion tensor imaging characterization and developmental change from childhood to adulthood

The presence of an anatomical connection between the orbitofrontal cortex and ventral striatum, forming a so‐called reward network, is well established across species. This connection has important implications for reward processing and is relevant to a number of neuropsychiatric disorders. Moreover, white matter (WM) is known to continue to mature across adolescence and into early adulthood, and developmental change in the reward network is an important component of models of decision making and risk taking. Despite the importance of this connection, the underlying WM has only recently been characterized in humans histologically, and not yet in‐vivo using brain imaging. Here, we implemented diffusion tensor imaging (DTI) in a large cross‐sectional sample of 295 healthy individuals ages 8–68 to further characterize the WM of this connection and its development from childhood into adulthood. We demonstrate that the accumbofrontal tract, connecting the orbitofrontal cortex and nucleus accumbens, can be identified using standard DTI sequences. Using Poisson modeling, we show that the accumbofrontal tract undergoes significant change across the lifespan, with males showing a higher and earlier peak compared to females. Moreover, the change occurs in a pattern consistent with developmental models of decision‐making. These findings support the hypothesis that developmental differences in WM integrity may be a contributing factor to the observed risk taking that occurs in adolescence. The accumbofrontal tract is not yet included in standard WM atlases, but may be important for inclusion in studies investigating fronto‐striatal networks, as well as in investigations of substance abuse and decision making. Hum Brain Mapp 36:4954–4963, 2015. © 2015 Wiley Periodicals, Inc .     

Multivariate patterns of brain-cognition associations relating to vulnerability and clinical outcome in the at-risk mental states for psychosis

Background: Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto‐temporo‐limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at‐risk mental states (ARMS) for psychosis. However, structure–cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques. Methods: Voxel‐based morphometry and partial least squares were employed to study system‐level covariance patterns between whole‐brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure–cognition covariance patterns were tested for significance and reliability using non‐parametric permutation and bootstrap resampling. Results: We identified ARMS‐specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto‐temporo‐limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions. Conclusions: These findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi‐domain neurocognitive measures to a set of prefronto‐temporo‐limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain–cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes. Hum Brain Mapp 33:2104–2124, 2012. © 2011 Wiley Periodicals, Inc.     

Relating empathy and emotion regulation: Do deficits in empathy trigger emotion dysregulation?

Emotion regulation is a crucial skill in adulthood; its acquisition represents one of the key developmental tasks in early childhood. Difficulties with adaptive emotion regulation increase the risk of psychopathology in childhood and adulthood. This is, for instance, shown by a relation between emotion regulation and aggressive behavior in childhood age, indicating emotion dysregulation as an important risk factor of aggressive behavior and potential precursor of psychopathology. Based on (1) interrelations between emotion processes and social information processing (maladaptive emotion regulation and social information processing are associated with higher levels of aggression) and (2) recent neuroscientific findings showing that empathy deficits might not only result in difficulties labeling others' emotions but one's own emotions too, we suggest that empathy deficits might serve as potential trigger of emotion dysregulation. Different studies investigating the relation between empathy and emotion regulation are presented and discussed. Discussions are based on the assumed potential of empathy deficits triggering emotion dysregulation. Furthermore, developmental neuroscientific findings on empathy and emotion regulation are highlighted which provide further insights on how these processes might relate. Finally, possible directions for future research are presented.     

The anticipation and outcome phases of reward and loss processing: A neuroimaging meta‐analysis of the monetary incentive delay task

The processing of rewards and losses are crucial to everyday functioning. Considerable interest has been attached to investigating the anticipation and outcome phases of reward and loss processing, but results to date have been inconsistent. It is unclear if anticipation and outcome of a reward or loss recruit similar or distinct brain regions. In particular, while the striatum has widely been found to be active when anticipating a reward, whether it activates in response to the anticipation of losses as well remains ambiguous. Furthermore, concerning the orbitofrontal/ventromedial prefrontal regions, activation is often observed during reward receipt. However, it is unclear if this area is active during reward anticipation as well. We ran an Activation Likelihood Estimation meta‐analysis of 50 fMRI studies, which used the Monetary Incentive Delay Task (MIDT), to identify which brain regions are implicated in the anticipation of rewards, anticipation of losses, and the receipt of reward. Anticipating rewards and losses recruits overlapping areas including the striatum, insula, amygdala and thalamus, suggesting that a generalised neural system initiates motivational processes independent of valence. The orbitofrontal/ventromedial prefrontal regions were recruited only during the reward outcome, likely representing the value of the reward received. Our findings help to clarify the neural substrates of the different phases of reward and loss processing, and advance neurobiological models of these processes.     

Hippocampal contributions to the processing of social emotions

Inducing and experiencing emotions about others' mental and physical circumstances is thought to involve self‐relevant processing and personal memories of similar experiences. The hippocampus is important for self‐referential processing during recall and prospection; however, its contributions during social emotions have not been systematically investigated. We use event‐related averaging and Granger causal connectivity mapping to investigate hippocampal contributions during the processing of varieties of admiration and compassion pertaining to protagonists' mental versus physical circumstances [admiration for virtue (AV) versus for skill; compassion for social/psychological pain (CSP) versus for physical pain]. Data were collected using a multistep emotion‐induction paradigm that included psychosocial interviews, BOLD fMRI, and simultaneous psychophysiological recording. Given that mnemonic demands were equivalent among conditions, we tested whether: (1) the hippocampi would be recruited more strongly and for a longer duration during the processing of AV and CSP; and (2) connectivity between the hippocampi and cortical systems involved in visceral somatosensation/emotional feeling, social cognitive, and self‐related processing would be more extensive during AV and CSP. Results elucidate the hippocampus' facilitative role in inducing and sustaining appropriate emotional reactions, the importance of self‐related processing during social emotions, and corroborate the conception that varieties of emotional processing pertaining to others' mental and physical situations engage at least partially distinct neural mechanisms. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

The neural basis of the abnormal self‐referential processing and its impact on cognitive control in depressed patients

Persistent pondering over negative self‐related thoughts is a central feature of depressive psychopathology. In this study, we sought to investigate the neural correlates of abnormal negative self‐referential processing (SRP) in patients with Major Depressive Disorder and its impact on subsequent cognitive control‐related neuronal activation. We hypothesized aberrant activation dynamics during the period of negative and neutral SRP in the rostral anterior cingulate cortex (rACC) and in the amygdala in patients with major depressive disorder. Additionally, we assumed abnormal activation in the fronto‐cingulate network during Stroop task execution. 19 depressed patients and 20 healthy controls participated in the study. Using an event‐related functional magnetic resonance imaging (fMRI) design, negative, positive and neutral self‐referential statements were displayed for 6.5 s and followed by incongruent or congruent Stroop conditions. The data were analyzed with SPM8. In contrast to controls, patients exhibited no significant valence‐dependent rACC activation differences during SRP. A novel finding was the significant activation of the amygdala and the reward‐processing network during presentation of neutral self‐referential stimuli relative to baseline and to affective stimuli in patients. The fMRI analysis of the Stroop task revealed a reduced BOLD activation in the right fronto‐parietal network of patients in the incongruent condition after negative SRP only. Thus, the inflexible activation in the rACC may correspond to the inability of depressed patients to shift their attention away from negative self‐related stimuli. The accompanying negative affect and task‐irrelevant emotional processing may compete for neuronal resources with cognitive control processes and lead thereby to deficient cognitive performance associated with decreased fronto‐parietal activation. Hum Brain Mapp 36:2781–2794, 2015. © 2015 Wiley Periodicals, Inc.     

Control of shared representations relies on key processes involved in mental state attribution

Action observation leads to the automatic activation of the corresponding motor representation in the observer through “mirror‐matching.” This constitutes a “shared representational system,” which is thought to subserve social understanding by motor simulation. However, it is unclear how these shared representations can be controlled and distinguished. Brain imaging suggests that controlling shared representations, indexed by the ability to control automatic imitative responses, activates anterior fronto‐median cortex (aFMC), and temporo‐parietal junction (TPJ). Crucially, these regions are also consistently implicated in mental state attribution and have provided an alternative account for higher‐level social cognition. Here, we directly tested whether social‐cognitive processes involve similar key computational mechanisms as the control of shared representations by using functional brain imaging to reveal overlapping brain circuits. We show in a within‐subject design that commonly activated regions occurred selectively in aFMC and TPJ. Mentalizing and self‐referential thoughts recruited a region in aFMC, which was also activated when controlling imitation. In the TPJ, an area overlapped between mentalizing, agency processing, and imitative control. Behavioral and neural correlates of mentalizing were further related to the individual ability for controlling imitation. Our findings support the assumption of shared key processes and suggest a novel link between embodied and social cognition. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Large‐scale white matter network reorganization in posttraumatic stress disorder

Recently, graph theoretical approaches applied to neuroimaging data have advanced understanding of the human brain connectome and its abnormalities in psychiatric disorders. However, little is known about the topological organization of brain white matter networks in posttraumatic stress disorder (PTSD). Seventy‐six patients with PTSD and 76 age, gender, and years of education‐matched trauma‐exposed controls were studied after the 2008 Sichuan earthquake using diffusion tensor imaging and graph theoretical approaches. Topological properties of brain networks including global and nodal measurements and modularity were analyzed. At the global level, patients showed lower clustering coefficient (p = .016) and normalized characteristic path length (p = .035) compared with controls. At the nodal level, increased nodal centralities in left middle frontal gyrus, superior and inferior temporal gyrus and right inferior occipital gyrus were observed (p < .05, corrected for false‐discovery rate). Modularity analysis revealed that PTSD patients had significantly increased inter‐modular connections in the fronto‐parietal module, fronto‐striato‐temporal module, and visual and default mode modules. These findings indicate a PTSD‐related shift of white matter network topology toward randomization. This pattern was characterized by an increased global network integration, reflected by increased inter‐modular connections with increased nodal centralities involving fronto‐temporo‐occipital regions. This study suggests that extremely stressful life experiences, when they lead to PTSD, are associated with large‐scale brain white matter network topological reconfiguration at global, nodal, and modular levels.     

Interrelation of resting state functional connectivity,striatal GABA levels,and cognitive control processes

Important issues for cognitive control are response selection processes, known to depend on fronto‐striatal networks with recent evidence suggesting that striatal gamma‐amino butyric acid (GABA) levels play an important role. Regional GABA concentrations have also been shown to modulate intrinsic connectivity, e.g. of the default mode network. However, the interrelation between striatal GABA levels, basal ganglia network (BGN) connectivity, and performance in cognitive control is elusive. In the current study, we measure striatal GABA levels using magnetic resonance spectroscopy (MRS) and resting state parameters using functional magnetic resonance imaging (fMRI). Resting state parameters include activity within the BGN, as determined by the low frequency power (LFP) within the network, and the functional connectivity between the BGN and somatomotor network (SMN). Specifically, we examine the interrelation between GABA, resting state parameters, and performance (i.e., accuracy) in conflict monitoring using a Simon task. Response control was affected by striatal GABA+ levels and activity within the BGN, especially when response selection was complicated by altered stimulus‐response mappings. The data suggest that there are two mechanisms supporting response selection accuracy. One is related to resting state activity within the BGN and modulated by striatal GABA+ levels. The other is related to decreased cortico‐striatal network connectivity, unrelated to the GABAergic system. The inclusion of all three factors (i.e., striatal GABA+ levels, activity within the BGN, and BGN‐SMN network connectivity) explained a considerable amount of variance in task accuracy. Striatal neurobiochemical (GABA+) and parameters of the resting state BGN represent important modulators of response control. Hum Brain Mapp 36:4383–4393, 2015. © 2015 Wiley Periodicals, Inc.     

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive-compulsive disorder

Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder. Objective: Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD. Method: Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task. Results: Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation. Conclusion: These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.