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Contains fulltext : 221606.pdf (Publisher’s version ) (Open Access) Observability of threat-related spatial attentional biases may require previous-trial responses associated with threat-related locations. This carryover effect might affect reliability and correlations. In Study 1, a diagonalized Visual Probe Task was completed online (N=131) with colour, anger, fear and disgust stimuli, with questionnaires on aggression, anxiety, depression and impulsivity. Bias towards negative stimuli was found only following previous targets on the negative location. Study 2 aimed to test an interpretation in terms of cue-evoked attention. Task variants were completed (N=101) with and without removal of the cue when targets appeared. Anger and disgust stimuli and aggression, anxiety and depression scales were used. Carryover was replicated with no interaction with cue offset. Over both tasks, reliability was low and no robust correlations with questionnaires were found. Carryover thus determined whether attentional bias to negative facial expressions was observed, but analyses taking this into account did not improve reliability or reveal correlations. 11 p.

Self-regulation refers to the ability to monitor and modulate emotions, behavior, and cognition, which in turn allows us to achieve goals and adapt to ever changing circumstances. This trait develops from early infancy well into adulthood, and features both low-level executive functions such as reactive inhibition, as well as higher level executive functions such as proactive inhibition. Development of self-regulation is linked to brain maturation in adolescence and adulthood. However, how self-regulation in daily life relates to brain functioning in pre-adolescent children is not known. To this aim, we have analyzed data from 640 children aged 8–11, who performed a stop-signal anticipation task combined with functional magnetic resonance imaging, in addition to questionnaire data on self-regulation. We find that pre-adolescent boys and girls who display higher levels of self-regulation, are better able to employ proactive inhibitory control strategies, exhibit stronger frontal activation and more functional coupling between cortical and subcortical areas of the brain. Furthermore, we demonstrate that pre-adolescent children show significant activation in areas of the brain that were previously only associated with reactive and proactive inhibition in adults and adolescents. Thus, already in pre-adolescent children, frontal-striatal brain areas are active during self-regulatory behavior., Highlights • Children with higher levels of self-regulation employ more proactive inhibition. • During proactive inhibition, children aged 8–11 show activation in frontal-cortical areas. • Children higher in self-regulation exhibit more cortical-subcortical coupling. • Children aged 8–11 show similar brain activation as adults during inhibition.

Contains fulltext : 235990.pdf (Publisher’s version ) (Open Access) Concerns have been raised about the low reliability of measurements of spatial attentional bias via RT differences in dot-probe tasks. The anticipatory form of the bias, directed towards predicted future stimuli, appears to have relatively good reliability, reaching around 0.70. However, studies thus far have not attempted to experimentally control task-related influence on bias, which could further improve reliability. Evoking top-down versus bottom-up conflict may furthermore reveal associations with individual differences related to mental health. In the current study, a sample of 143 participants performed a predictive Visual Probe Task (predVPT) with angry and neutral face stimuli online. In this task, an automatic bias is induced via visually neutral cues that predict the location of an upcoming angry face. A task-relevant bias was induced via blockwise shifts in the likely location of target stimuli. The bias score resulting from these factors was calculated as RTs to target stimuli at locations of predicted but not actually presented angry versus neutral faces. Correlations were tested with anxiety, depression, self-esteem and aggression scales. An overall bias towards threat was found with a split-half reliability of 0.90, and 0.89 after outlier removal. Avoidance of threat in blocks with a task-relevant bias away from threat was correlated with anxiety, with correction for multiple testing. The same relationship was nominally significant for depression and low self-esteem. In conclusion, we showed high reliability of spatial attentional bias that was related to anxiety. 7 p.

Highlights • Dorsal attention network (DAN) centrality increased during stress recovery in healthy controls. • Healthy siblings of schizophrenia patients show a similar increase during stress recovery. • Bipolar disorder patients show no network changes during stress recovery., Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress.

Highlights • Test-retest reliability of structural MRI and DWI data was good. • Test-retest reliability of resting-state and task-related fMRI was moderate. • Overall, global brain measures are more reliable than local brain measures., The YOUth cohort study is a unique longitudinal study on brain development in the general population. As part of the YOUth study, 2000 children will be included at 8, 9 or 10 years of age and planned to return every three years during adolescence. Magnetic resonance imaging (MRI) brain scans are collected, including structural T1-weighted imaging, diffusion-weighted imaging (DWI), resting-state functional MRI and task-based functional MRI. Here, we provide a comprehensive report of the MR acquisition in YOUth Child & Adolescent including the test-retest reliability of brain measures derived from each type of scan. To measure test-retest reliability, 17 adults were scanned twice with a week between sessions using the full YOUth MRI protocol. Intraclass correlation coefficients were calculated to quantify reliability. Global brain measures derived from structural T1-weighted and DWI scans were reliable. Resting-state functional connectivity was moderately reliable, as well as functional brain measures for both the inhibition task (stop versus go) and the emotion task (face versus house). Our results complement previous studies by presenting reliability results of regional brain measures collected with different MRI modalities. YOUth facilitates data sharing and aims for reliable and high-quality data. Here we show that using the state-of-the art YOUth MRI protocol brain measures can be estimated reliably.

The loss of ventral striatal dopaminergic neurons in Parkinson's disease (PD) predicts an impact on the reward system. The ventrostriatal system is involved in motivational processing and its dysfunction may be related to non-motor symptoms such as depression and apathy. We previously documented that patients with PD had blunted Blood Oxygen Level Dependent functional magnetic resonance imaging (BOLD fMRI) reward task related activity during both reward anticipation (i.e., in the ventral striatum) and reward outcome (i.e., in the orbitofrontal cortex). Evidence for the modulation of brain function by dopaminergic genes in PD is limited. Genes implicated in dopamine transmission, such as the dopamine transporter gene (DAT1) may influence the clinical heterogeneity seen in PD, including reward processing. This study therefore sought to determine whether genetic differences in the DAT gene are associated with brain activity associated with response to reward in PD patients and controls. A sample of PD cases on treatment (n = 15) and non-PD controls (n = 30) from an ethnic group unique to South Africa were genotyped. We found a three-way interaction between GENOTYPE × BOLD fMRI REWARD × DIAGNOSIS [F (1, 40) = 4.666, p = 0.037, partial η2 = 0.104]. PD patients with the DAT1 homozygous 10/10 repeat genotype showed a relative decrease in orbitofrontal cortex reward outcome related activity compared to the patient group who did not have this repeat. PD patients with other genotypes showed an expected increase in orbitofrontal cortex reward outcome related activity compared to controls. Given the small sample size of the PD group with the 10/10 repeat, these results should be considered preliminary. Nevertheless, these preliminary findings highlight the potential modulation of dopamine transporter polymorphisms on orbitofrontal reward system activity in PD and highlight the need for further studies.

Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

Background Studies of pre-and post-treatment striatal volume in schizophrenia have reported conflicting results. Materials and methods We assessed dorsal striatal (caudate and putamen) volumes bilaterally in 22 never-treated, non-substance-abusing patients with first-episode schizophrenia or schizophreniform disorder and 23 healthy controls matched for age, sex and educational status. Patients received either risperidone or flupenthixol long acting injection and were compared by structural MRI with controls at weeks 0, 4 and 13. T1-weighted data on a 3T MRI scanner were obtained and images were reconstructed using FreeSurfer. Treatment outcome was assessed by changes in psychopathology, insight, functionality, cognitive performance and motor symptoms. Results Caudate, but not putamen volumes was significantly larger in patients bilaterally at baseline (P = 0.01). Linear mixed effects repeated measures found no significant group × time interactions for any of the regions. Caudate volume was not significantly associated with improvements in psychotic symptoms. Also, the findings of a regression model were inconsistent insofar as larger caudate volume was associated with less improvement in depression scores, greater improvement in functionality and greater improvement in verbal learning but less improvement in reasoning and problem solving (left caudate) and composite cognitive score (right caudate). Conclusions The increased caudate volumes prior to treatment are contrary to previous reports in never-treated patients with first-episode schizophrenia, and together with our failure to demonstrate volume changes related to acute treatment, call into question previous proposals that enlarged caudate volume is a consequence of antipsychotic treatment.

Stress is a major risk factor for almost all psychiatric disorders, however, the underlying neurobiological mechanisms remain largely elusive. In healthy individuals, a successful stress response involves an adequate neuronal adaptation to a changing environment. This adaptive response may be dysfunctional in vulnerable individuals, potentially contributing to the development of psychopathology. In the current study, we investigated brain responses to emotional stimuli following stress in healthy controls and at-risk individuals. An fMRI study was conducted in healthy male controls (N = 39) and unaffected healthy male siblings of schizophrenia patients (N = 39) who are at increased risk for the development of a broad range of psychiatric disorders. Brain responses to pictures from the International Affective Picture System (IAPS) were measured 33 min after exposure to stress induced by the validated trier social stress test (TSST) or a control condition. Stress-induced levels of cortisol, alpha-amylase, and subjective stress were comparable in both groups. Yet, stress differentially affected brain responses of schizophrenia siblings versus controls. Specifically, control subjects, but not schizophrenia siblings, showed reduced brain activity in key nodes of the default mode network (PCC/precuneus and mPFC) and salience network (anterior insula) as well as the STG, MTG, MCC, vlPFC, precentral gyrus, and cerebellar vermis in response to all pictures following stress. These results indicate that even in the absence of a psychiatric disorder, at-risk individuals display abnormal functional activation following stress, which in turn may increase their vulnerability and risk for adverse outcomes.

The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with frontostriatal dysfunction. While frontostriatal systems play a key role in behavioral inhibition, there are to our knowledge no fMRI studies investigating the potential impact of HIV on systems involved during the inhibition of voluntary movement. A total of 17 combined antiretroviral therapy (cART) naïve HIV+ participants as well as 18 age, gender, ethnic, education matched healthy controls performed a modified version of the stop-signal paradigm. This paradigm assessed behavior as well as functional brain activity associated with motor execution, reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing before stopping). HIV+ participants showed significantly slower responses during motor execution compared to healthy controls, whereas they had normal proactive response slowing. Putamen hypoactivation was evident in the HIV+ participants based on successful stopping, indicating subcortical dysfunction during reactive inhibition. HIV+ participants showed normal cortical functioning during proactive inhibition. Our data provide evidence that HIV infection is associated with subcortical dysfunction during reactive inhibition, accompanied by relatively normal higher cortical functioning during proactive inhibition. This suggests that HIV infection may primarily involve basic striatal-mediated control processes in cART naïve participants. (JINS, 2015, 21, 722–731)

OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to investigate the effects of HIV infection on reward processing by examining the function of the ventral-striatal reward system during a monetary incentive delay task. DESIGN: This is a cross-sectional case-control study. METHODS: Eighteen combined antiretroviral therapy-naive HIV-positive (HIV+) participants, as well as 16 matched healthy controls, performed a monetary incentive delay task. This paradigm assesses behaviour as well as functional brain activity-associated reward anticipation and reward outcome. RESULTS: HIV+ participants showed a general decrease in activation associated with both neutral as well as potentially rewarding cues in their ventral striatum. We found normal activity related to reward outcome in the orbito-frontal cortex. Despite HIV+ participants' reaction times being significantly slower when independently measured from the reward paradigm, this performance deficit normalized during the performance of the reward task. CONCLUSION: HIV caused a decrease in activity during cue processing in the ventral striatum, with normal cortical functioning during reward outcome processing. Our results therefore suggest that HIV not only has an impact on fronto-striatal systems involved in executive functioning, but also has a direct impact on the function of the ventral-striatal reward system.

Healthy aging is associated with a progressive decline across a range of cognitive functions. An important factor underlying this decline may be the age-related impairment in stimulus-reward processing. Several studies have investigated age-related effects, but compared young versus old subjects. This is the first study to investigate the effect of aging on brain activation during reward processing within a continuous segment of the adult life span. We scanned 49 healthy adults aged 40-70 years, using functional MRI. We adopted a simple reward task, which allowed separate evaluation of neural responses to reward anticipation and receipt. The effect of reward on performance accuracy and speed was not related to age, indicating that all subjects could perform the task correctly. We identified a whole-brain significant age-related decline of ventral striatum activation during reward anticipation as compared to neutral anticipation. Importantly, the specificity of this finding was underscored by the observation that there was no general decline in activation during anticipation. Activation in the ventral striatum increased with age during reward receipt as compared to receiving neutral outcome. Finally, activation in the ventromedial prefrontal cortex during outcome was not affected by age. Our data demonstrate that the typical shift in striatal activation from reward receipt to reward anticipation in young adults disappears with healthy aging. These changes are consistent the well-ocumented age-related decline of striatal dopamine availability, and may provide a stepping stone for further research of age-related neurodegenerative diseases.

Response inhibition involves proactive and reactive modes. Proactive inhibition is goal-directed, triggered by warning cues, and serves to restrain actions. Reactive inhibition is stimulus-driven, triggered by salient stop-signals, and used to stop actions completely. Functional MRI studies have identified brain regions that activate during proactive and reactive inhibition. It remains unclear how these brain regions operate in functional networks, and whether proactive and reactive inhibition depend on common networks, unique networks, or a combination. To address this we analyzed a large fMRI dataset (N = 65) of a stop-signal task designed to measure proactive and reactive inhibition, using independent component analysis (ICA). We found 1) three frontal networks that were associated with both proactive and reactive inhibition, 2) one network in the superior parietal lobe, which also included dorsal premotor cortex and left putamen, that was specifically associated with proactive inhibition, and 3) two right-lateralized frontal and fronto-parietal networks, including the right inferior frontal gyrus and temporoparietal junction as well as a bilateral fronto-temporal network that were uniquely associated with reactive inhibition. Overlap between networks was observed in dorsolateral prefrontal and parietal cortices. Taken together, we offer a new perspective on the neural underpinnings of inhibitory control, by showing that proactive inhibition and reactive inhibition are supported by a group of common and unique networks that appear to integrate and interact in frontoparietal areas.

HIV-associated neurocognitive disorder (HAND) is a frequently occurring comorbidity of HIV infection. Evidence suggests this condition starts subclinical before a progression to a symptomatic stage. Blood oxygenated level dependent (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in an early stage and might therefore be useful to evaluate the effect of HIV infection on brain function. An extensive literature search was performed in June 2015. Eligibility criteria for included studies were as follows: (1) conducting with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative control group. A total of 19 studies were included in the review including 931 participants. Differences in activation between HIV-positive and -negative participants were found when testing multiple domains, i.e., attention, (working) memory, and especially executive functioning. Overall, HIV-positive patients showed hyperactivation in task-related brain regions despite equal performances as controls. Task performance was degraded only for the most complex tasks. A few studies investigated the effect of aging on fMRI, and most of them found no interaction with HIV infection. Only three studies evaluated the effect of combination antiretroviral therapy (cART) on functional data suggesting an increase in activation with the use of cART. fMRI is a sensitive instrument to detect subtle cognitive changes in HIV patients. Open questions remain regarding the effects of cART on fMRI and the effects of aging on fMRI. Electronic supplementary material The online version of this article (doi:10.1007/s13365-016-0483-y) contains supplementary material, which is available to authorized users.

Background: Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated. Methods: Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues). Results: We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group. Limitations: Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups. Conclusion: Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit.

Adolescence is a transitional period between childhood and adulthood and is characterized by emotional instability. Underlying this behavior may be an imbalance between the limbic subcortical areas and the prefrontal cortex. Here, we investigated differences in these regions during adolescence and young adulthood. Fifty subjects aged 10 to 24 viewed and rated neutral, negative, and positive pictures (IAPS: International Affective Picture System), while being scanned with functional MRI. Only those trials in which there was a match between the subject's response and the IAPS rating were included in the analyses. Task performance (matching accuracy, reaction times) did not differ across age. Activity in the amygdala and hippocampus decreased with age when processing emotional salient stimuli versus neutral stimuli. In contrast, activation in the ventrolateral prefrontal cortex increased with age. Importantly, we show for the first time that these age-related changes are paralleled by an increase in functional coupling of the amygdala and hippocampus with the orbitofrontal cortex and ventrolateral prefrontal cortex. These findings are in line with the general notion that brain development from childhood to adulthood is characterized by a gradual increase in frontal control over subcortical regions. Understanding these developmental changes is important as these may underlie typical adolescent behavior.

Functional MRI studies investigating the impact of HIV on the brain have implicated the involvement of fronto-striatal circuitry. However, to date there is no review and meta-analysis of this work. We systematically reviewed the literature and performed a meta-analysis of functional magnetic resonance imaging (fMRI) studies in HIV-infected individuals using a well validated tool recently developed for use in fMRI, 'GingerALE'. Twenty-one studies (468 HIV+, 270 HIV- controls) were qualitatively reviewed, of which six (105 HIV+, 102 controls) utilized fMRI paradigms engaging the fronto-striatal-parietal network, making a quantitative analysis possible. Our meta-analysis revealed consistent functional differences in the left inferior frontal gyrus and caudate nucleus between infected participants and controls across these studies. This fronto-striatal dysfunction was qualitatively related to cognitive impairment, disease progression and treatment effects. Although further work needs to be done to further delineate the potentially confounding influence of substance abuse and HIV-related comorbidities, as well as HIV's effect on functional haemodynamic vascular coupling, these findings indicate that further investigation of the fronto-striatal sub-networks in HIV-infected patients is warranted.

During adolescence, functional and structural changes in the brain facilitate the transition from childhood to adulthood. Because the cortex and the striatum mature at different rates, temporary imbalances in the frontostriatal network occur. Here, we investigate the development of the subcortical and cortical components of the frontostriatal network from early adolescence to early adulthood in 60 subjects in a cross-sectional design, using functional MRI and a stop-signal task measuring two forms of inhibitory control: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping). During development, reactive inhibition improved: older subjects were faster in reactive inhibition. In the brain, this was paralleled by an increase in motor cortex suppression. The level of proactive inhibition increased, with older subjects slowing down responding more than younger subjects when anticipating a stop-signal. Activation increased in the right striatum, right ventral and dorsal inferior frontal gyrus, and supplementary motor area. Moreover, functional connectivity during proactive inhibition increased between striatum and frontal regions with age. In conclusion, we demonstrate that developmental improvements in proactive inhibition are paralleled by increases in activation and functional connectivity of the frontostriatal network. These data serve as a stepping stone to investigate abnormal development of the frontostriatal network in disorders such as schizophrenia and attention-deficit hyperactivity disorder.

Item does not contain fulltext Learning from feedback involves a network of various cortical and subcortical regions. Although activation in this network has been shown to be especially strong in successful learners, it is currently unclear which of these regions are related to within-subject variation in learning performance. To this aim, 21 subjects performed a probabilistic feedback-learning task consisting of multiple independent Learning blocks and non-learning Control blocks, while functional magnetic resonance imaging data were acquired. In agreement with previous studies, activation in anterior, lateral and medial left prefrontal cortex, insula and superior and inferior parietal cortical regions were found when contrasting Learning and Control blocks. Furthermore, activation in the supplementary motor area, anterior cingulate cortex and bilateral striatum was associated specifically with the learning phase and not the application phase during Learning blocks. Finally, activation only in the ventral striatum was associated with within-subject learning performance across the Learning blocks. Taken together, these latter two results are argued to provide the answer to the main research question: ventral striatum activation is associated with within-subject variations in learning performance. The ventral striatum appears to play a vital role in learning by adjusting behavior based on feedback. 9 p.

Impaired insight is a hallmark feature of schizophrenia. Structural studies implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior temporal brain regions. The cortical midline structures (CMS) are also implicated in functional studies primarily through self-reflective processing tasks. However, few studies have explored the relationship between white matter tracts and insight in schizophrenia, and none in first-episode schizophrenia (FES). Here, we examined for fractional anisotropy (FA) differences in 89 minimally treated FES patients and 98 matched controls, and identified those FA differences associated with impaired clinical insight in patients. We found widespread FA reduction in FES patients compared to controls. Poorer insight in patients was predicted by lower FA values in a number of white matter tracts with a predilection for tracts associated with cortical midline structures (fronto-occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata), and more severe depressive symptoms. The association between FA abnormalities and insight was most robust for the awareness of symptoms and illness awareness domains. Our study implicates a network of tracts involved in impaired insight in schizophrenia with a predilection for the CMS. This study is a first step in delineating the white matter tracts involved in insight impairment in schizophrenia prior to chronicity.

In about 30–50% of patients with posttraumatic stress disorder (PTSD), symptoms persist after treatment. Although neurobiological research has advanced our understanding of PTSD, little is known about the neurobiology underlying persistence of PTSD. Two functional MRI scans were collected from 72 war veterans with and without PTSD over a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. All participants performed a trauma-unrelated emotional processing task in the scanner. Based on post-treatment symptom severity, a distinction was made between remitted and persistent patients. Behavioral and imaging measures of trauma-unrelated emotional processing were compared between the three groups (remitted patients, N=21; persistent patients, N=22; and combat controls, N=25) with repeated-measures (pre- and post-treatment) analyses. Second, logistic regression was used to predict treatment outcome. Before and after treatment, persistent patients showed a higher dorsal anterior cingulate cortex (dACC) and insula response to negative pictures compared with remitted patients and combat controls. Before treatment, persistent patients showed increased amygdala activation in response to negative pictures compared with remitted patients. The remitted patients and combat controls did not differ on the behavioral or imaging measures. Finally, higher dACC, insula, and amygdala activation before treatment were significant predictors of symptom persistence. Our results highlight a pattern of brain activation that may predict poor response to PTSD treatment. These findings can contribute to the development of alternative or additional therapies. Further research is needed to elucidate the heterogeneity within PTSD and describe how differences in neural function are related to treatment outcome. Such approaches are critical for defining parameters to customize PTSD treatment and improve treatment response rates.

A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n = 21) and noncarriers (n = 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location.

Bipolar disorder (BD) is characterized by abnormalities in emotion processing. Specifically, the processing of affective faces appears to be impaired. This study explored functional abnormalities in the neural network underlying the processing of facial affect in three different mood states (euthymic, depressed, and manic) associated with BD. Functional magnetic resonance imaging (fMRI) data were acquired from 18 healthy controls and 18 euthymic, 12 depressed, and 12 manic BD patients while viewing affective or neutral faces. Compared with controls, BD patients in all mood states showed reduced activation in the bilateral orbitofrontal cortex (OFC), indicating that activation in this region is independent of mood state. Activation in the amygdala, dorsolateral prefrontal cortex (DLPFC), and right temporal pole depended on mood state. Whereas activation levels of depressed patients were not significantly different from those of controls, activation levels in both euthymic and manic patients were significantly reduced compared with activation levels of both controls and depressed patients. However in the right DLPFC euthymic patients showed an increased level of activation compared with manic patients. These results add to the evidence for functional deficits in the affective network in BD patients, of which reduced bilateral OFC activation was found to be the most pronounced deficit across all mood states. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Abnormalities in the frontal lobe are considered to be central to the pathology of schizophrenia. Neuroimaging studies indeed report abnormal function of the frontal lobe in schizophrenia patients. However, the nature of these functional abnormalities is unclear, in particular whether they are affected by medication. We therefore investigated whether frontal functioning is already abnormal in first-episode medication-naive schizophrenia, and if so, if this dysfunction is related to symptomatology. Thirty medication-naive male patients with first-episode schizophrenia and 36 matched healthy controls performed a modified working memory task while fMRI data were acquired. During the task, subjects were presented with novel task (NT) and practiced task (PT) memory sets. Compared to controls, patients showed reduced performance during NT and PT. However, both groups performed better during PT, indicating that practice improved performance. Importantly, practice reduced brain activation in both patients and controls, but this effect of practice was significantly smaller in patients compared to controls, specifically in the left dorsolateral prefrontal cortex (DLPFC; p=0.01). The reduced effect of practice on brain activation was related to the severity of negative symptoms and disorganization. These results suggest that DLPFC function is deficient in the early phases of schizophrenia and cannot be attributed to the use of antipsychotics.

Background Offspring of patients with schizophrenia and bipolar disorder are at increased risk to develop psychopathology. It has been suggested that the development of these disorders may be a result of early neurodevelopmental abnormalities. The intracranial volume (ICV) is a direct marker for neurodevelopment in the early years, as ICV reaches 90% of its full size around the age of five. Interestingly, a smaller ICV is more consistently found in SZ patients, compared to controls, than in bipolar disorder patients. The offspring of these two patients group may provide important information on the putative neurodevelopmental trajectory underlying the development of these disorders. We compared ICV between offspring of at least one parent with SZ (SZo) or BD (BDo) and control offspring (Co) in relation to IQ and the presence of psychopathology. Methods A large sample of children and adolescents (8–18 years old; 54 SZo, 90 BDo, and 46 Co) was included. T1-weighted (3-Tesla) MRI brain scans were available for 146 participants. Group differences in ICV, global and local brain measures, psychopathology (K-SADS-PL, CBCL/6–18), IQ (WISC-III/WAIS-III), and their interactions were analyzed. FreeSurfer-5.3.0 was used for subcortical and cortical volume, cortical thickness, and cortical surface area estimations. Groups were compared using linear mixed effects modeling, corrected for family dependencies. FDR-correction was applied. Results Our main finding was that ICV was significantly smaller in SZo, compared to BDo and Co. IQ was significantly lower in both SZo and BDo, relative to Co, but could not explain the smaller ICV in SZo. ICV was also not explained by psychopathology, even though there was no significant difference in ‘any psychopathology’ between SZo and BDo. There was however some illness specificity as BDo had a higher prevalence of ‘any mood disorder’ as compared with Co, and SZo had a higher prevalence of major depressive disorder and autism spectrum disorders as compared with BDo and Co. After correcting for ICV, the cortex was significantly thinner in SZo compared to BDo and Co, and BDo had larger lateral ventricles than Co. Without correction for ICV, volumes of the total brain and gray matter were significantly smaller in SZo than in BDo and Co. Cortical white matter volume was significantly smaller in SZo as compared with Co. Discussion Irrespective of a lower IQ and increased presence of psychopathology in both high-risk offspring groups, abnormal early brain development, expressed as smaller ICV, differentiates offspring of patients with schizophrenia from offspring of patients with bipolar disorder and offspring of healthy parents. This suggest that the risk for schizophrenia is, in contrast to that in bipolar disorder, characterized by stunted brain development.

Cannabis is one of the most used drugs of abuse. It affects the brain reward system in animals, and has proven rewarding and addictive potential in humans. We used functional MRI to measure brain activity during reward anticipation in a monetary reward task. Long-term cannabis users were compared to healthy controls. An additional control group consisting of nicotine users was included. Cannabis users showed attenuated brain activity during reward anticipation in the nucleus accumbens compared to non-smoking controls, but not compared to smoking controls. Cannabis users showed decreased reward anticipation activity in the caudate nucleus, compared to both non-smoking and smoking controls. These data suggest that nicotine may be responsible for attenuated reward anticipation activity in the accumbens, but that differences in the caudate are associated with the use of cannabis. Our findings imply that chronic cannabis use as well as nicotine, may cause an altered brain response to rewarding stimuli.

The relative contribution of dominant and non-dominant language networks to recovery from aphasia is a matter of debate. We assessed with functional magnetic resonance imaging (fMRI) to what extent the left and right hemispheres are associated with recovery from aphasia after stroke. fMRI with three language tasks was performed in 13 aphasic stroke patients and in 13 healthy subjects. Severity of aphasia was examined within 2 months after stroke and after at least 1 year. Recovery of naming ability and scores on the Token Test were correlated with data from fMRI in the chronic phase. A breath-hold paradigm was used to investigate hemodynamic responsiveness.Overall language performance in the chronic phase correlated with higher relative activation of left compared to right perisylvian areas. Recovery of naming ability was positively correlated with activation in the left inferior frontal gyrus (IFG) for semantic decision and verb generation. Recovery on the Token Test was positively correlated with activation in both left and right IFG during semantic decision and verb generation. Hemodynamic response to the breath-hold task was similar in patients and controls.Our study suggests that in the chronic stage after stroke left IFG activity is associated with improvement of picture naming and sentence comprehension, whereas activity in the right IFG may reflect up-regulation of non-linguistic cognitive processing. Altered hemodynamic responsiveness seems an unlikely confounder in the interpretations of fMRI results.

It is well known that parts of a visual scene are prioritized for visual processing, depending on the current situation. How the CNS moves this focus of attention across the visual image is largely unknown, although there is substantial evidence that preparation of an action is a key factor. Our results support the view that direct corticocortical feedback connections from frontal oculomotor areas to the visual cortex are responsible for the coupling between eye movements and shifts of visuospatial attention. Functional magnetic resonance imaging (fMRI)–guided transcranial magnetic stimulation (TMS) was applied to the frontal eye fields (FEFs) and intraparietal sulcus (IPS). A single pulse was delivered 60, 30, or 0 ms before a discrimination target was presented at, or next to, the target of a saccade in preparation. Results showed that the known enhancement of discrimination performance specific to locations to which eye movements are being prepared was enhanced by early TMS on the FEF contralateral to eye movement direction, whereas TMS on the IPS resulted in a general performance increase. The current findings indicate that the FEF affects selective visual processing within the visual cortex itself through direct feedback projections.

Impaired social cognition is a frequently observed and disabling characteristic of schizophrenia. An important aspect of social cognition involves making social decisions about others. The present study investigates whether brain activity related to social decision-making differs between patients with schizophrenia and healthy controls. Twelve patients with schizophrenia and 21 control subjects participated in the study. Behavioral performance and brain activity were assessed during a task that involved judging the trustworthiness of faces. We performed region-of-interest-based analyses, which revealed that patients with schizophrenia display specific increases and reductions in activation of the medial orbitofrontal cortex, amygdala and the right insula during social decision-making, areas that play key roles in the network that underlies social decisions. These findings suggest that the impairments in social cognition that are often observed in schizophrenia are, at least in part, related to altered brain activity in these areas. (c) 2007 Elsevier Inc. All rights reserved.

Schizophrenia is a psychiatric disorder that is associated with impaired functioning of the fronto-striatal network, in particular during reward processing. However, it is unclear whether this dysfunction is related to the illness itself or whether it reflects a genetic vulnerability to develop schizophrenia. Here, we examined reward processing in unaffected siblings of schizophrenia patients using functional magnetic resonance imaging. Brain activity was measured during reward anticipation and reward outcome in 27 unaffected siblings of schizophrenia patients and 29 healthy volunteers using a modified monetary incentive delay task. Task performance was manipulated online so that all subjects won the same amount of money. Despite equal performance, siblings showed reduced activation in the ventral striatum, insula, and supplementary motor area (SMA) during reward anticipation compared to controls. Decreased ventral striatal activation in siblings was correlated with sub-clinical negative symptoms. During the outcome of reward, siblings showed increased activation in the ventral striatum and orbitofrontal cortex compared to controls. Our finding of decreased activity in the ventral striatum during reward anticipation and increased activity in this region during receiving reward may indicate impaired cue processing in siblings. This is consistent with the notion of dopamine dysfunction typically associated with schizophrenia. Since unaffected siblings share on average 50% of their genes with their ill relatives, these deficits may be related to the genetic vulnerability for schizophrenia.

Background Schizophrenia patients have difficulty inhibiting automatic saccades. Many studies have failed to resolve whether healthy first-degree relatives share the same deficit. Measures of brain activity may be more sensitive than behavioral measures. In patients, the saccadic inhibition deficit has been related to impaired frontostriatal functioning. This study attempts to establish whether this abnormality is also present in unaffected relatives of patients. Methods Functional brain images were acquired during prosaccades and antisaccades in 16 control subjects and 16 unaffected siblings of schizophrenia patients using an event-related functional magnetic resonance imaging design. Eye movements were measured during scanning. Results The task activated a network of regions corresponding to the oculomotor system. Siblings and control subjects did not differ during execution of prosaccades. During antisaccades, siblings did not activate the caudate nucleus. Siblings and control subjects did not differ on the percentage of antisaccade errors. Conclusions Siblings did not appropriately activate the striatum during antisaccades, similar to what has been reported in patients. Siblings, however, did not make significantly more errors during antisaccades, indicating that they were able to compensate for the inactive caudate. Future research is needed to assess the potential of this striatal deficit as (genetic) risk factor for schizophrenia.

Reduced spatial negative priming (SNP) in schizophrenia is commonly attributed to the inability to filter out irrelevant information. However, some investigators have suggested that reduced SNP in patients is caused by either perceptual mismatching or salience of the distracter. The goal of the present study was to determine the influence of these perceptual processes. In this preliminary report, we present data of 15 schizophrenia patients on atypical medication and 15 matched healthy controls. Compared to controls, patients showed a reduced SNP effect, even when controlled for perceptual mismatching. This reduced effect was not affected by distracter salience.

18th Annual Conference of the International Society for Bipolar Disorders & 8th Biennial Conference of the InternationalSociety for Affective Disorders, July 13–16, 2016, Amsterdam, The Netherlands

Little is known about the underlying neural mechanism of deep brain stimulation (DBS). We found that DBS targeted at the nucleus accumbens (NAc) normalized NAc activity, reduced excessive connectivity between the NAc and prefrontal cortex, and decreased frontal low-frequency oscillations during symptom provocation in patients with obsessive-compulsive disorder. Our findings suggest that DBS is able to reduce maladaptive activity and connectivity of the stimulated region.

article i nfo Background:Impairedworkingmemory(WM)isahallmarkofschizophrenia.Inadditiontoclassical WMregions such as the dorsolateral prefrontal cortex (DLPFC) and the striatum, dysfunctions in the default-mode network (DMN) contribute to these WM deficits. Unaffected siblings of patients also show WM impairments. However, the nature of the functional deficits underlying these impairments is unclear, mainly because of impaired perfor- mance confounding neuroimaging results. Methods: Here, we investigated WM and DMN activity in 23 unaffected siblings of schizophrenia patients and 24 healthy volunteers using fMRI and a Sternberg WM task. WM load was determined prior to scanning to ensure 90% accuracy for all subjects. Results: Siblings showed hyperactivation during the encoding phase of WM in the right medial prefrontal cortex (MPFC) which is the anterior part of the DMN. No differences were found during the maintenance phase. During the retrieval phase, siblings showed hyperactivation in WM regions: DLPFC, inferior parietal cortex and the striatum. Siblings who showed hyperactivity in the MPFC during encoding showed DLPFC and striatum hyperactivation during retrieval. Conclusions:Our findingofhyperactivationinWMandDMNareasindicatesthatsiblingsfailtoadequatelyinhibit DMN activity during demanding cognitive tasks and subsequently hyperactivate WM areas. This failure may re- flect dopamine hyperactivity in the striatum which prevents adequate DMN suppression needed for effective WM. This study provides support for the notion that aberrant WM and DMN activation patterns may represent candidate endophenotypes for schizophrenia.

Stopping an action requires suppression of the primary motor cortex (M1). Inhibitory control over M1 relies on a network including the right inferior frontal cortex (rIFC) and the supplementary motor complex (SMC), but how these regions interact to exert inhibitory control over M1 is unknown. Specifically, the hierarchical position of the rIFC and SMC with respect to each other, the routes by which these regions control M1, and the causal involvement of these regions in proactive and reactive inhibition remain unclear. We used off-line repetitive TMS to perturb neural activity in the rIFC and SMC followed by fMRI to examine effects on activation in the networks involved in proactive and reactive inhibition, as assessed with a modified stop-signal task. We found repetitive TMS effects on reactive inhibition only. rIFC and SMC stimulation shortened the stop-signal RT (SSRT) and a shorter SSRT was associated with increased M1 deactivation. Furthermore, rIFC and SMC stimulation increased right striatal activation, implicating frontostriatal pathways in reactive inhibition. Finally, rIFC stimulation altered SMC activation, but SMC stimulation did not alter rIFC activation, indicating that rIFC lies upstream from SMC. These findings extend our knowledge about the functional organization of inhibitory control, an important component of executive functioning, showing that rIFC exerts reactive control over M1 via SMC and right striatum.

The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating behavior according to anticipated rewards. However, the precise temporal landscape of their electrophysiological interactions in humans remains unknown because it is not possible to record neural activity from the nucleus accumbens using noninvasive techniques. We recorded electrophysiological activity simultaneously from the nucleus accumbens and cortex (via surface EEG) in humans who had electrodes implanted as part of deep‐brain‐stimulation treatment for obsessive–compulsive disorder. Patients performed a simple reward motivation task previously shown to activate the ventral striatum. Spectral Granger causality analyses were applied to dissociate “top–down” (cortex → nucleus accumbens)‐ from “bottom–up” (nucleus accumbens → cortex)‐directed synchronization (functional connectivity). “Top–down”‐directed synchrony from cortex to nucleus accumbens was maximal over medial frontal sites and was significantly stronger when rewards were anticipated. These findings provide direct electrophysiological evidence for a role of the MFC in modulating nucleus accumbens reward‐related processing and may be relevant to understanding the mechanisms of deep‐brain stimulation and its beneficial effects on psychiatric conditions. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

Contains fulltext : 102466.pdf (Publisher’s version ) (Open Access) Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF): a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF) were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of monkey studies favoring the caudate nucleus over the putamen in the search for oculomotor functions. 17 p.

Background Inhibitory control is central to executive functioning and appears deficient in schizophrenia. However, it is unclear how inhibitory control is affected, what the underlying neural mechanisms are, whether these deficits are related to the illness itself or to increased risk for the illness, and whether there is a relation to impairments in other executive functions. Methods We used functional magnetic resonance imaging to investigate two forms of inhibitory control: proactive inhibition (anticipation of stopping) and reactive inhibition (outright stopping). Twenty-four schizophrenia patients, 24 unaffected siblings, and 24 healthy control subjects performed a modified version of the stop-signal paradigm. To assess the relation between performance on inhibitory control and other executive functions, we correlated inhibitory control indices with working memory span. Results Compared with control subjects, proactive inhibition was reduced in patients and siblings. Reactive inhibition was unaffected. Reduced proactive inhibition was associated with a failure to activate the right striatum, the right inferior frontal cortex, and the left and right temporoparietal junction. Activation during reactive inhibition was unaffected. Those patients with the least proactive inhibition also showed the shortest working memory span. Conclusions These results suggest that schizophrenia is associated with reduced proactive inhibition, probably resulting from corticostriatal dysfunction. This deficit is related to an increased risk for schizophrenia and likely reflects a general executive function deficit rather than a specific inhibitory control impairment.

Diminished functional lateralization in language-related areas is found in chronic schizophrenia. It is not clear at what stage of illness these abnormalities in lateralization arise, or whether they are affected by medication. In addition, it is hypothesized that reduced language lateralization is related to positive symptoms of schizophrenia, but studies addressing this issue have yielded contradictory results. In this study we used functional MRI to measure language lateralization in 35 first-episode medication-naive schizophrenia patients and 43 matched healthy controls. Subjects performed three language tasks: a paced verb generation task, an antonym generation task, and a semantic decision task. Lateralization Index (LI) was calculated, using a relative threshold technique, in seven Regions of Interest (ROIs), including the main language-related areas and their contralateral homologues. In addition, we investigated whether language lateralization was correlated with psychotic symptoms. Across all ROIs, LI was significantly reduced in patients (p

Background Schizophrenia is characterized by impaired social cognition, including emotion processing. Behavioral studies have reported impaired performance on various emotion processing tasks, and imaging studies in patients have observed aberrant activity within the underlying neural circuitry. Also, subjects at increased genetic risk of developing schizophrenia, including unaffected siblings of patients, show behavioral impairments in emotion processing. It is unclear, however, whether and how the underlying neural system is disrupted in these subjects. In this study, we investigated whether siblings of patients with schizophrenia show abnormal brain activation during basic emotion processing. Methods Brain activity was measured using functional magnetic resonance imaging in 24 unaffected siblings of patients with schizophrenia and 25 healthy control subjects while they viewed and rated neutral, positive, and negative pictures. None of the subjects had a psychiatric disorder, and the two groups did not differ in age, gender, or level of own, paternal, or maternal education. Results Compared with control subjects, siblings showed increased activity within the amygdala, hippocampus, medial prefrontal cortex, posterior and anterior cingulate cortex, and middle temporal gyrus in response to emotionally arousing pictures relative to neutral pictures. No activation differences between the groups were found during the neutral stimuli, indicating that the observed hyperactivity is likely caused by abnormal emotion processing rather than impaired visuoattentional processing. Conclusions Our findings of hyperactivity in siblings during emotion processing suggest that functional abnormalities within the neural circuitry of emotion processing are related to the genetic risk for developing schizophrenia.

Background Obsessive-compulsive disorder (OCD) is primarily conceived as an anxiety disorder but has features resembling addictive behavior. Patients with OCD may develop dependency upon compulsive behaviors because of the rewarding effects following reduction of obsession-induced anxiety. Reward processing is critically dependent on ventral striatal-orbitofrontal circuitry and brain imaging studies in OCD have consistently shown abnormal activation within this circuitry. This is the first functional imaging study to investigate explicitly reward circuitry in OCD. Methods Brain activity during reward anticipation and receipt was compared between 18 OCD patients and 19 healthy control subjects, using a monetary incentive delay task and functional magnetic resonance imaging. Reward processing was compared between OCD patients with predominantly contamination fear and patients with predominantly high-risk assessment. Results Obsessive-compulsive disorder patients showed attenuated reward anticipation activity in the nucleus accumbens compared with healthy control subjects. Reduced activity of the nucleus accumbens was more pronounced in OCD patients with contamination fear than in patients with high-risk assessment. Brain activity during reward receipt was similar between patients and control subjects. A hint toward more dysfunctional reward processing was found in treatment-resistant OCD patients who subsequently were successfully treated with deep brain stimulation of the nucleus accumbens. Conclusions Obsessive-compulsive disorder patients may be less able to make beneficial choices because of altered nucleus accumbens activation when anticipating rewards. This finding supports the conceptualization of OCD as a disorder of reward processing and behavioral addiction.

BACKGROUND: Stopping a manual response requires suppression of the primary motor cortex (M1) and has been linked to activation of the striatum. Here, we test three hypotheses regarding the role of the striatum in stopping: striatum activation during successful stopping may reflect suppression of M1, anticipation of a stop-signal occurring, or a slower response build-up. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-four healthy volunteers underwent functional magnetic resonance imaging (fMRI) while performing a stop-signal paradigm, in which anticipation of stopping was manipulated using a visual cue indicating stop-signal probability, with their right hand. We observed activation of the striatum and deactivation of left M1 during successful versus unsuccessful stopping. In addition, striatum activation was proportional to the degree of left M1 deactivation during successful stopping, implicating the striatum in response suppression. Furthermore, striatum activation increased as a function of stop-signal probability and was to linked to activation in the supplementary motor complex (SMC) and right inferior frontal cortex (rIFC) during successful stopping, suggesting a role in anticipation of stopping. Finally, trial-to-trial variations in response time did not affect striatum activation. CONCLUSIONS/SIGNIFICANCE: The results identify the striatum as a critical node in the neural network associated with stopping motor responses. As striatum activation was related to both suppression of M1 and anticipation of a stop-signal occurring, these findings suggest that the striatum is involved in proactive inhibitory control over M1, most likely in interaction with SMC and rIFC.

Almost all cortical areas in the vertebrate brain take part in recurrent connections through the subcortical basal ganglia (BG) nuclei, through parallel inhibitory and excitatory loops. It has been suggested that these circuits can modulate our reactions to external events such that appropriate reactions are chosen from many available options, thereby imposing volitional control over behavior. The saccade system is an excellent model system to study cortico-BG interactions. In this study two possible pathways were investigated that might regulate automaticity of eye movements in the human brain; the cortico-tectal pathway, running directly between the frontal eye fields (FEF) and superior colliculus (SC) and the cortico-striatal pathway from the FEF to the SC involving the caudate nucleus (CN) in the BG. In an event-related functional magnetic resonance imaging (fMRI) paradigm participants made pro- and anti-saccades. A diffusion tensor imaging (DTI) scan was made for reconstruction of white matter tracts between the FEF, CN and SC. DTI fiber tracts were used to divide both the left and right FEF into two sub-areas, projecting to either ipsilateral SC or CN. For each of these FEF zones an event-related fMRI timecourse was extracted. In general activity in the FEF was larger for anti-saccades. This increase in activity was lateralized with respect to anti-saccade direction in FEF zones connected to the SC but not for zones only connected to the CN. These findings suggest that activity along the contralateral FEF–SC projection is responsible for directly generating anti-saccades, whereas the pathway through the BG might merely have a gating function withholding or allowing a pro-saccade.

Activity within the default‐mode network (DMN) is thought to be related to self‐referential processing, such as thinking about one's preferences or personality traits. Although the DMN is generally considered to function as a network, evidence is starting to accumulate that suggests that areas of the DMN are each specialized for different subfunctions of self‐referential processing. Here, we address the issue of functional specialization by investigating changes in coupling between areas of the DMN during self‐referential processing. To this aim, brain activity was assessed during a task in which subjects had to indicate whether a trait adjective described their own personality (self‐referential, Self condition), that of another person (other‐referential, Other condition), or whether the trait was socially desirable (nonreferential, Control condition). To exclude confounding effects of cardiorespiratory processes on activity and functional coupling, we corrected the fMRI signal for these effects. Activity within areas of the DMN was found to be modulated by self‐referential processing. More specifically, during the Self condition compared to the Other and Control condition, activity within the dorsal medial prefrontal cortex, ventral medial prefrontal cortex, and posterior cingulate cortex was increased. Moreover, coupling between areas of the DMN was reduced during the Self condition compared to the Other and Control condition, while coupling between regions of the DMN and regions outside the network was increased. As such, these results provide an indication for functional specialization within the DMN and support the notion that each area of the DMN is involved in different subfunctions of self‐referential processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

Functional magnetic resonance imaging (fMRI) can be used to detect experimental effects on brain activity across measurements. The success of such studies depends on the size of the experimental effect, the reliability of the measurements, and the number of subjects. Here, we report on the stability of fMRI measurements and provide sample size estimations needed for repeated measurement studies. Stability was quantified in terms of the within-subject standard deviation (sigma(w)) of BOLD signal changes across measurements. In contrast to correlation measures of stability, this statistic does not depend on the between-subjects variance in the sampled group. Sample sizes required for repeated measurements of the same subjects were calculated using this sigma(w). Ten healthy subjects performed a motor task on three occasions, separated by one week, while being scanned. In order to exclude training effects on fMRI stability, all subjects were trained extensively on the task. Task performance, spatial activation pattern, and group-wise BOLD signal changes were highly stable over sessions. In contrast, we found substantial fluctuations (up to half the size of the group mean activation level) in individual activation levels, both in ROIs and in voxels. Given this large degree of instability over sessions, and the fact that the amount of within-subject variation plays a crucial role in determining the success of an fMRI study with repeated measurements, improving stability is essential. In order to guide future studies, sample sizes are provided for a range of experimental effects and levels of stability. Obtaining estimates of these latter two variables is essential for selecting an appropriate number of subjects.