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Obsessive–compulsive disorder (OCD) is highly heterogeneous. While obsessions often involve fear of harm, many patients report uncomfortable sensations and/or urges that drive repetitive behaviors in the absence of a specific fear. Prior work suggests that urges in OCD may be similar to everyday “urges‐for‐action” (UFA) such as the urge to blink, swallow, or scratch, but very little work has investigated the pathophysiology underlying urges in OCD. In the current study, we used an urge‐to‐blink approach to model sensory‐based urges that could be experimentally elicited and compared across patients and controls using the same task stimuli. OCD patients and controls suppressed eye blinking over a period of 60 s, alternating with free blinking blocks, while brain activity was measured using functional magnetic resonance imaging. OCD patients showed significantly increased activation in several regions during the early phase of eyeblink suppression (first 30 s), including mid‐cingulate, insula, striatum, parietal cortex, and occipital cortex, with lingering group differences in parietal and occipital regions during late eyeblink suppression (last 30 s). There were no differences in brain activation during free blinking blocks, and no conditions where OCD patients showed reduced activation compared to controls. In an exploratory analysis of blink counts performed in a subset of subjects, OCD patients were less successful than controls in suppressing blinks. These data indicate that OCD patients exhibit altered brain function and behavior when experiencing and suppressing the urge to blink, raising the possibility that the disorder is associated with a general abnormality in the UFA system that could ultimately be targeted by future treatments.

The habenula (Hb) inhibits dopaminergic reward signaling in response to negative outcomes and has been linked to numerous functional domains relevant to mental health, including reward prediction, motivation, and aversion processing. Despite its important neuroscientific and clinical implications, however, the human Hb remains poorly understood due to its small size and the associated technical hurdles to in vivo functional magnetic resonance imaging (fMRI) investigation. Using high-resolution 3 T fMRI data from 68 healthy young adults acquired through the Human Connectome Project, we developed a rigorous approach for mapping the whole-brain resting-state functional connectivity of the human Hb. Our study combined an optimized strategy for defining subject-level connectivity seeds to maximize Hb blood-oxygen-level-dependent (BOLD) signal sensitivity with high-quality surface-based alignment for robust functional localization and cortical sensitivity. We identified significant positive Hb connectivity with: (i) conserved brainstem targets, including the dopaminergic ventral tegmental area, serotonergic raphe nuclei, and periaqueductal gray; (ii) subcortical structures related to reward and motor function, including the nucleus accumbens, dorsal striatum, pallidum, thalamus, and cerebellum; and (iii) cortical areas associated with the Salience Network and early sensory processing, including the dorsal anterior cingulate, anterior insula, and primary visual and auditory cortices. Hb connectivity was strongly biased towards task-positive brain regions, with weak or negative connectivity observed throughout the task-negative Default Mode Network. Our study provides a detailed characterization of Hb resting-state functional connectivity in healthy young adults, demonstrating both the feasibility and clinical potential of studying the human Hb using high-resolution 3 T fMRI.

Background Inflammation has been hypothesized to contribute to reward dysfunction across psychiatric conditions, but little is known about this relationship in youth. Therefore, the present study investigated the associations between general and specific markers of inflammation and neural activation during reward processing, including anticipation and attainment, in youth with diverse psychiatric symptoms. Methods Forty-six psychotropic medication-free youth with diverse psychiatric symptoms underwent a blood draw to measure 41 cytokines, as well as structural and functional magnetic resonance imaging. The Reward Flanker Task examined neural activation during reward anticipation and attainment. Relationships between inflammation and neural activation were assessed using data reduction techniques across the whole-brain, as well as in specific reward regions of interest (basal ganglia, anterior and mid-cingulate cortex [ACC/MCC]). Results Whole-brain principal component analyses showed that factor 3 (12 cytokines: FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF) was negatively correlated with precuneus/posterior cingulate cortex activity during anticipation. Factor 2 (11 cytokines: eotaxin, IL-1α, IL-1Rα, IL-2, IL-5, IL-9, IL-12p40, IL-13, IL-15, MCP-3, and TNF-β) was negatively correlated with angular gyrus activity during attainment. ROI analyses additionally showed that multiple cytokines were related to activity in the basal ganglia (EGF, FGF-2, Flt-3L, IL-2, IL-13, IL-15, IL-1Rα, MCP-3) and ACC/MCC (Flt-3L) during attainment. C-reactive protein (CRP) was not associated with neural activation. Conclusions Investigation of specific markers of immune function showed associations between inflammatory processes and activation of posterior default mode network, prefrontal cortex, and basal ganglia regions during multiple phases of reward processing.

Sensory phenomena (SP) are aversive or uncomfortable sensations that accompany and/or drive repetitive behaviors in obsessive-compulsive disorder (OCD). Although SP are associated with significant distress and may respond less well to standard treatments than harm-related obsessions, little is known about their underlying neurobiology. The present study used functional magnetic resonance imaging (fMRI) to measure brain functioning related to severity of SP during a “body-focused” videos task designed to elicit activation in sensorimotor brain regions. Regression analysis examined the relationship between severity of SP and activation during task using permutation analysis with threshold-free cluster enhancement, corrected for multiple comparisons (family-wise error rate p

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

Accepted Manuscript, BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -20.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD., This research was funded by the Max Planck Society (Germany). Additional funding was from the Japan Society for the Promotion of Science (KAKENHI Grant No. 18K15523 [to YA], KAKENHI Grant No. 16K04344 [to YH], KAKENHI Grant Nos. 16K19778 and 18K07608 [to TNakam], and KAKENHI Grant No. 26461762 [to AN]); the Carlos III Health Institute (Grant No. PI14/00419 [to PA], Grant No. PI040829 cofunded by European Regional Development Fund [to LL], Grant No. FI17/00294 [to IM-Z], Grant No. PI16/00950 [to JMM], and Grant Nos. CPII16/00048, PI13/01958, and PI16/00889 cofunded by European Regional Development Funds [to CS-M]); the Ontario Mental Health Foundation (Research Training Fellowship [to SHA]); Alberta Innovates Translational Health Chair in Child and Youth Mental Health (to PDA), the Ontario Brain Institute (to PDA); the National Institute of Mental Health (Grant No. K23MH104515 [to JTB], Grant No. K23-MH092397 [to BPB], Grant No. K23MH082176 [to KDF), Grant No. R21MH101441 [to RM], Grant No. R01MH081864 [to JO and JP], and Grant No. R01MH085900 [to JO and JF], Grant No. R21MH093889 [to HBS]); Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant No. 2011/21357–9 [to MCB], Grant No. 2011/21357–9 [to GFB], Grant No. 2011/21357–9 [to MQH], and Grant No. 2011/21357–9 [to ECM]); the Swiss National Science Foundation (Grant No. 320030_130237 [to SB; principal investigator, Susanne Walitza]); the Hartmann Müller Foundation (Grant No. 1460 [to SB]); the David Judah Fund at the Massachusetts General Hospital (to BPB); EU FP7 Project TACTICS (Grant No. 278948 [to JB]); the National Natural Science Foundation of China (Grant No. 81560233 [to YC] and Grant No. 81371340 [to ZW]); the International OCD Foundation (Grant No. K23 MH115206 [to PG]); the Wellcome Sir Henry Dale Fellowship (Grant No. 211155/Z/18/Z [to TUH]); the Jacobs Foundation (to TUH); the Brain and Behavior Research Foundation (2018 NARSAD Young Investigator Grant No. 27023 [to TUH]); the Agency for Medical Research and Development (Grant No. JP18dm0307002 [to YH]); the Michael Smith Foundation for Health Research (to FJ-F); the Federal Ministry of Education and Research of Germany (Grant No. BMBF-01GW0724 [to NK]); the Deutsche Forschungsgemeinschaft (Grant No. KO 3744/7–1 [to KK]); the Helse Vest Health Authority (Grant Nos. 911754 and 911880 [to GK]); the Norwegian Research Council (Grant No. HELSEFORSK 243675 [to GK]); the Marató TV3 Foundation (Grant Nos. 01/2010 and 091710 [to LL]); the Agency for Management of University and Research Grants (Grant No. 2017 SGR 881 [to LL] and 2017 SGR 1247 from the Generalitat de Catalunya [to JMM]); Fundação para a Ciência e a Tecnologia (Grant No. PDE/BDE/113604/2015 from the PhD-iHES Program [to RM], Grant No. PDE/BDE/113601/2015 from the PhD-iHES Program [to PSM]); the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research (Grant Nos. 22591262, 25461732, and 16K10253 [to TNakao]); the Government of India Department of Science and Technology (DST INSPIRE Faculty Grant No. -IFA12-LSBM-26 [to JCN] and Grant No. SR/S0/HS/0016/2011 [to YCJR]); the Government of India Department of Biotechnology (Grant No. BT/06/IYBA/2012 [to JCN] and Grant No. BT/PR13334/Med/30/259/2009 [to YCJR]); the New York State Office of Mental Health (to HBS); the Italian Ministry of Health (Grant No. RC13-14-15-16A [to GS]); the National Center for Advancing Translational Sciences (Grant No. UL1TR000067/KL2TR00069 [to ERS]); the Canadian Institutes of Health Research (to SES); the Michael Smith Foundation for Health Research (to SES); the British Columbia Provincial Health Services Authority (to SES); the Netherlands Organization for Scientific Research (Grant No. NWO/ZonMW Vidi 917.15.318 [to GAvW]); the Wellcome-DBT India Alliance (Grant No. 500236/Z/11/Z [to GV]); the Shanghai Key Laboratory of Psychotic Disorders (Grant No. 13dz2260500 [to ZW]).

Several psychiatric disorders involve abnormalities of interoception and associated neural circuitry centered on the insula. The development of interventions modulating interoceptive circuits could lead to novel treatment approaches for these disorders. The 5-HT3 receptor antagonist ondansetron is a good candidate for the modulation of interoceptive circuits, as 5-HT3 receptors are located abundantly on sensory pathways and ondansetron has shown some clinical utility in disorders characterized by sensory and interoceptive abnormalities. The present study tested the ability of three different doses of ondansetron to engage neural regions involved in interoception to determine the drug’s utility as a therapeutic agent to target circuit abnormalities in patients. Fifty-three healthy subjects were randomized to receive a single 8-mg (n = 18), 16-mg (n = 17), or 24-mg (n = 18) dose of ondansetron and placebo before MRI scanning on separate days. Subjects performed an fMRI task previously shown to engage interoceptive circuitry in which they viewed videos depicting body movements/sensation and control videos. The results revealed a highly significant relationship between dosage and activation in bilateral insula, somatosensory and premotor regions, cingulate cortex, and temporal cortex for control but not body-focused videos. These effects were driven by a robust reduction in activation for ondansetron compared to placebo for the 24-mg group, with weaker effects for the 16-mg and 8-mg groups. In conclusion, high-dose ondansetron reduces activation of several areas important for interoception, including insula and sensorimotor cortical regions. This study reveals the potential utility of this drug in modulating hyperactivity in these regions in patients.

Obsessive-compulsive disorder (OCD) patients show increased insula activation to disgust-inducing images compared to healthy controls (HC). We explored whether this disgust reactivity was also present in the olfactory domain by conducting the first fMRI study of olfaction in OCD. Neural activation in response to pleasant and unpleasant odors (vs. unscented air) was investigated in 15 OCD and 15 HC participants using fMRI. OCD participants (vs. HC) had increased left anterior insula activation to unpleasant odors (vs. unscented air), which positively correlated with their disgust sensitivity and ratings of the unpleasantness and intensity of those odors. OCD participants (vs. HC) showed increased activation of caudate nucleus and left anterior and posterior insula to pleasant odors (vs. unscented air), which positively correlated with their OCD symptom severity, trait anxiety, frequency of feeling disgust, and odor intensity ratings. OCD participants had increased anterior insula activation to both pleasant and unpleasant odors, which correlated with their OCD symptoms, anxiety, disgust sensitivity, and frequency of feeling disgust. OCD patients might have a negative cognitive bias and experience all stimuli, regardless of valence, as being more unpleasant than healthy people. These findings further elucidate the neural underpinnings of OCD and may contribute to more effective treatments.

Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research.

Age-related improvements in human performance monitoring have been linked to maturation of medial frontal cortex (MFC) in healthy youth, however, imaging studies conflict regarding age-related changes in MFC activation patterns. Topographical analysis of single-subject activation enables measurement of variation in location of MFC activation by age, as well as other potentially influential factors (e.g., performance on task). In this study, 22 youth (ages 8 - 17 years) and 21 adults (ages 23 - 51 years) underwent functional magnetic resonance imaging during a performance monitoring task examining interference and errors. Single-subject factors (extent of MFC activation, age and accuracy) were entered into a three-level hierarchical linear model to test the influence of these characteristics on location of MFC activation. Activation shifted from a rostral/anterior to a more dorsal/posterior location with increasing age and accuracy during interference. Inclusion of age and accuracy accounted for almost all of the unexplained variance in location of interference-related activation within MFC. This pattern links improvement of performance-monitoring capacity to age-related increases in posterior MFC and decreases in anterior MFC activation. Taken together, these results show the maturation of performance monitoring capacity to depend on more focal engagement of posterior MFC substrate for cognitive control.

Obsessive-compulsive disorder (OCD) is characterized by excessive absorption with internally-generated distressing thoughts and urges, with difficulty incorporating external information running counter to their fears and concerns. In the present study, we experimentally probed this core feature of OCD through the use of a novel attention switching task that investigates transitions between internally focused (IF) and externally focused (EF) attentional states. Eighteen OCD patients and 18 controls imagined positive and negative personal event scenarios (IF state) or performed a color-word Stroop task (EF state). The IF/EF states were followed by a target detection (TD) task requiring responses to external stimuli. Compared to controls, OCD patients made significantly more errors and showed reduced activation of superior and inferior occipital cortex, thalamus, and putamen during TD following negative IF, with the inferior occipital hypoactivation being significantly greater for TD following negative IF compared to TD following the other conditions. Patients showed stronger functional connectivity between the inferior occipital region and dorsomedial prefrontal cortex. These findings point to an OCD-related impairment in the visual processing of external stimuli specifically when they follow a period of negative internal focus, and suggest that future treatments may wish to target the transition between attentional states.

Background In recent years, diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in obsessive–compulsive disorder (OCD). However, findings have been inconsistent, and it is unclear whether WM abnormalities are related to cognitive processes. The aim of this study was to explore the relationship of WM alterations with cognitive variables in OCD in order to investigate the structural correlates of behaviorally relevant features of the disorder. Methods We compared DTI-derived fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) measures between OCD patients (n = 16) and healthy controls (n = 18) using a whole-brain tract-based spatial statistics (TBSS) approach. We also explored the correlations of WM alterations with clinical and cognitive variables. Results Patients with OCD demonstrated increases in MD in the bilateral posterior corona radiata; left anterior corona radiata; bilateral superior longitudinal fasciculus; genu, body, and splenium of the corpus callosum; and left posterior limb of the internal capsule. An increase in RD values was also found in some of the same tracts (right posterior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, and corpus callosum). Furthermore, increased MD value in the internal capsule was correlated with the percentage of errors made during a target detection task, which was greater in the OCD group overall. Conclusions These findings indicate that OCD patients show greater diffusivity in several white-matter regions. The correlation between cognitive performance and diffusivity in the internal capsule suggests that microstructural WM alternations may have functional consequences for the disorder.

Obsessive-compulsive disorder (OCD) is often associated with pathological uncertainty regarding whether an action has been performed correctly or whether a bad outcome will occur, leading to compulsive "evidence gathering" behaviors aimed at reducing uncertainty. The current study used event-related functional magnetic resonance imaging to investigate neural functioning in OCD patients and controls as subjective certainty was rated in response to sequential pieces of evidence for a decision. Uncertainty was experimentally manipulated so that some decisions were associated with no "objective" uncertainty (all observed evidence pointed to one correct choice), whereas other decisions contained calculable but varying levels of objective uncertainty based on displayed probabilities. Results indicated that OCD patients differed from controls on decisions that contained no objective uncertainty, such that patients rated themselves as more uncertain. Patients also showed greater activation in a network of brain regions previously associated with internally-focused thought and valuation including ventromedial prefrontal cortex, parahippocampus, middle temporal cortex, as well as amygdala and orbitofrontal cortex/ventral anterior insula. In the patient group, a significantly greater number of positive intersubject correlations were found among several of these brain regions, suggesting that this network is more interconnected in patients. OCD patients did not differ from controls on decisions where task parameters led to uncertainty. These results indicate that OCD is associated with hyperactivation in a network of limbic/paralimbic brain regions when making decisions, which may contribute to the greater subjective experience of doubt that characterizes the disorder.

Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.

Despite the fact that OCD patients show altered decision making in everyday life, few studies have investigated how patients make risky decisions and what contextual factors impact choices. We investigated cognitive context with the use of the "framing effect" task, which investigates decision making based on whether monetarily equivalent choice options are framed in terms of a potential to either lose (lose $20 out of $50) or gain (gain $30 out of $50) money. In addition, we manipulated social context by providing positive or neutral feedback on subjects' choices. Overall, participants were risk taking for options framed in terms of potential loss and risk averse for options framed in terms of potential gain (the classic framing effect). Although OCD patients were generally more risk averse, the effect of the frame on choices did not differ significantly from healthy participants and choices were not impacted by social context. Within OCD patients, greater self-reported indecisiveness was associated with a larger effect of the frame on choices. OCD patients were also significantly slower to make choices in the loss compared to gain frame, an effect that was not observed among healthy participants. Overall, our results suggest that the framing of choice options has a differential effect on decision times but not the actual choices made by OCD patients, and that patients are not sensitive to social feedback when making choices. The correlation between indecisiveness and the framing effect in OCD suggests that further work interrogating the relationship between specific symptoms and decision making among patients may yield new insights into the disorder.

Top-down attentional control is required when subjects must attend to one of multiple conflicting stimulus features, such as in the Stroop task. Performance may be improved when such control is implemented in advance of stimulus presentation, yet few studies have examined this issue. Our investigation employed a spatial Stroop task with a manual response, allowing us to focus on the effects of preparatory attention on verbal processing when it is the less automatic attribute. A letter cue (P or W) presented for 2200 msec instructed subjects to respond on the basis of the position or meaning of a word (up, down, left, right) placed in an incongruent position relative to center. Event-related potentials recorded during pre- and poststimulus periods were analyzed as a function of reaction time to the target stimulus (fast vs. slow) in order to differentiate neural activity associated with more or less successful implementation of control. During the prestimulus period, fast responses to subsequent targets were associated with enhanced slow-wave activity over right frontal and bilateral central-parietal regions. During the poststimulus period, fast word trials were uniquely associated with an enhanced inferior temporal negativity (ITN) from 200 to 600 msec. More importantly, a correlation between frontal prestimulus activity and the poststimulus ITN suggested that frontal preparatory activity played a role in facilitating conceptual processing of the verbal stimulus when it arrived, providing an important link between preparatory attention and mechanisms that improve performance in the face of conflict.

The authors explored the effect of Parkinson's disease (PD) on the generation and maintenance of response readiness in a simple reaction time task. They compared performance of idiopathic PD patients without dementia, age-matched controls, and younger controls over short (1-, 3-, and 6-s) and long (12- and 18-s) foreperiod intervals. After each trial, the authors probed memory for visual information that also had to be maintained during the trial interval. Patients and controls did not differ overall in their ability to maintain readiness over long delays. However, within the PD group only, errors in maintaining visual information were correlated with difficulty in maintaining readiness, suggesting that systems impaired in PD may facilitate the maintenance of processing in both motor and cognitive domains.

Efficient, adaptive behavior relies on the ability to flexibly move between internally focused (IF) and externally focused (EF) attentional states. Despite evidence that IF cognitive processes such as event imagination comprise a significant amount of awake cognition, the consequences of internal absorption on the subsequent recruitment of brain networks during EF tasks are unknown. The present functional magnetic resonance imaging (fMRI) study employed a novel attentional state switching task. Subjects imagined positive and negative events (IF task) or performed a working memory task (EF task) before switching to a target detection (TD) task also requiring attention to external information, allowing for the investigation of neural functioning during external attention based on prior attentional state. There was a robust increase of activity in frontal, parietal, and temporal regions during TD when subjects were previously performing the EF compared with IF task, an effect that was most pronounced following negative IF. Additionally, dorsolateral prefrontal cortex was less negatively coupled with ventromedial prefrontal and posterior cingulate cortices during TD following IF compared with EF. These findings reveal the striking consequences for brain activity following immersion in an IF attentional state, which have strong implications for psychiatric disorders characterized by excessive internal focus.

Prior research links greater activation of posterior medial frontal cortex (pMFC) and anterior insula (AI) with decreasing outcome predictability during decision making, as measured by decreasing probability for the more likely outcome out of two or increasing outcome variance. In addition to predictability, much work indicates that the magnitude or ‘stakes’ of the outcome is also important. Despite the interest in the neural correlates of these decision variables, it is unknown whether pMFC and AI are differentially sensitive to predictability when magnitude is varied. This study examined brain activity during decision making in relation to decreasing outcome predictability for low as compared with high magnitude decisions. For low magnitude decisions, reduced predictability of the outcome was associated with greater activity in pMFC and bilateral AI, replicating prior studies. In contrast, there was no relationship between predictability and brain activity for high magnitude decisions, which tended to elicit greater pMFC and AI activity than low magnitude decisions for more predictable outcomes. These data indicate that the relationship between outcome predictability and pMFC and AI activity during decision making depends on magnitude, and suggest that these regions may be responding to the motivational salience of the decision rather than predictability information per se.

Background: Obsessive-compulsive disorder (OCD) is characterized by an excessive focus on upsetting or disturbing thoughts, feelings, and images that are internally-generated. Internally-focused thought processes are subserved by the ‘‘default mode network’’ (DMN), which has been found to be hyperactive in OCD during cognitive tasks. In healthy individuals, disengagement from internally-focused thought processes may rely on interactions between DMN and a frontoparietal network (FPN) associated with external attention and task execution. Altered connectivity between FPN and DMN may contribute to the dysfunctional behavior and brain activity found in OCD. Methods: The current study examined interactions between FPN and DMN during rest in 30 patients with OCD (17 unmedicated) and 32 control subjects (17 unmedicated). Timecourses from seven fronto-parietal seeds were correlated across the whole brain and compared between groups. Results: OCD patients exhibited altered connectivity between FPN seeds (primarily anterior insula) and several regions of DMN including posterior cingulate cortex, medial frontal cortex, posterior inferior parietal lobule, and parahippocampus. These differences were driven largely by a reduction of negative correlations among patients compared to controls. Patients also showed greater positive connectivity between FPN and regions outside DMN, including thalamus, lateral frontal cortex, and somatosensory/motor regions. Conclusions: OCD is associated with abnormal intrinsic functional connectivity between large-scale brain networks. Alteration of interactions between FPN and DMN at rest may contribute to aspects of the OCD phenotype, such as patients’ inability to disengage from internally-generated scenarios and thoughts when performing everyday tasks requiring external attention.

Objective Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal–striatal–thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal cortex) follow unique maturational trajectories, and altered connectivity within distinct loops may be differentially associated with OCD at specific stages of development. Method Altered development of striatal and thalamic connectivity to medial frontal cortex was tested in 60 OCD patients compared with 61 healthy control subjects at child, adolescent, and adult stages of development, using resting-state functional connectivity MRI. Results OCD in the youngest patients was associated with reduced connectivity of dorsal striatum and medial dorsal thalamus to rostral and dorsal anterior cingulate cortex, respectively. Increased connectivity of dorsal striatum to ventral medial frontal cortex was observed in patients at all developmental stages. In child patients, reduced connectivity between dorsal striatum and rostral anterior cingulate cortex correlated with OCD severity. Conclusions Frontal–striatal–thalamic loops involved in cognitive control are hypoconnected in young patients near illness onset, whereas loops implicated in emotion processing are hyperconnected throughout the illness.

Some decisions are made after obtaining several pieces of information, while others are reached quickly. Such differences may depend on the quality of information acquired, as well as individual variability in how cautiously evidence is evaluated. The current study examined neural activity while subjects accumulated sequential pieces of evidence and then made a decision. Uncertainty was updated with each piece of evidence, with individual ratings of subjective uncertainty characterizing underconfidence when observing evidence. Increased uncertainty during evidence accumulation was associated with activity in dorsal anterior cingulate cortex, whereas greater uncertainty when executing a decision uniquely elicited lateral frontal and parietal activity. Greater underconfidence when observing evidence correlated with activity in ventromedial prefrontal cortex. These results suggest that neural mechanisms of uncertainty depend on the stage of decision-making (belief updating versus decision), and that greater subjective uncertainty when evaluating evidence is associated with activity in ventromedial brain regions, even in the absence of overt risk.

Patients with obsessive-compulsive disorder (OCD) show an increased error-related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder-specific. Descriptors: Error-related negativity (ERN), Event-related potentials (ERPs), Anxiety, Anterior cingulate cortex (ACC)

Despite its critical role in performance-monitoring, the development of posterior medial prefrontal cortex (pMFC) in goal-directed behaviors remains poorly understood. Performance monitoring depends on distinct, but related functions that may differentially activate the pMFC, such as monitoring response conflict and detecting errors. Developmental differences in conflict- and error-related activations, coupled with age-related changes in behavioral performance, may confound attempts to map the maturation of pMFC functions. To characterize the development of pMFC-based performance monitoring functions, we segregated interference and error-processing, while statistically controlling for performance.Twenty-one adults and 23 youth performed an event-related version of the Multi-Source Interference Task during functional magnetic resonance imaging (fMRI). Linear modeling of interference and error contrast estimates derived from the pMFC were regressed on age, while covarying for performance.Interference- and error-processing were associated with robust activation of the pMFC in both youth and adults. Among youth, interference- and error-related activation of the pMFC increased with age, independent of performance. Greater accuracy associated with greater pMFC activity during error commission in both groups.Increasing pMFC response to interference and errors occurs with age, likely contributing to the improvement of performance monitoring capacity during development.