Revisiting deficits in threat and safety appraisal in obsessive-compulsive disorder.

Current behavioural treatment of obsessive-compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re-evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N = 45) and matched healthy controls (N = 45) underwent functional magnetic resonance imaging. While in the scanner, participants completed a well-validated fear reversal task and a resting-state scan. We found no evidence for group differences in task-evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain-behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r = 0.39, pFWE = .001). These findings suggest that changes in conditioned threat-related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning.

Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

A Brief Executive Language Screen for Frontal Aphasia.

Aphasia assessment tools have primarily focused on classical aphasia type and severity, with minimal incorporation of recent findings that suggest a significant role of executive control operations in language generation. Assessment of the interface between language and executive functions is needed to improve detection of spontaneous speech difficulties. In this study we develop a new Brief Executive Language Screen (BELS), a brief tool specifically designed to assess core language and executive functions shown to be involved in spontaneous generation of language. Similar to other measures of aphasia, the BELS assesses articulation and core language skills (repetition, naming and comprehension). Unique additions to the BELS include assessments of spontaneous connected speech, word fluency (phonemic/semantic) and sentence completion (verbal initiation, inhibition and selection). One-hundred and eight healthy controls and 136 stroke patients were recruited. Confirmatory factor analysis was used to determine construct validity and logistic regression was used to evaluate the discriminative validity, informing the final version of the BELS. The results showed that the BELS is sensitive for articulation and nominal language deficits, and it measures executive aspects of spontaneous language generation, which is a hallmark of frontal dynamic aphasia. The results have encouraging theoretical and practical implications.

Evidence against benefits from cognitive training and transcranial direct current stimulation in healthy older adults.

Cognitive training and brain stimulation show promise for ameliorating age-related neurocognitive decline. However, evidence for this is controversial. In a Registered Report, we investigated the effects of these interventions, where 133 older adults were allocated to four groups (left prefrontal cortex anodal transcranial direct current stimulation (tDCS) with decision-making training, and three control groups) and trained over 5 days. They completed a task/questionnaire battery pre- and post-training, and at 1- and 3-month follow-ups. COMT and BDNF Val/Met polymorphisms were also assessed. Contrary to work in younger adults, there was evidence against tDCS-induced training enhancement on the decision-making task. Moreover, there was evidence against transfer of training gains to untrained tasks or everyday function measures at any post-intervention time points. As indicated by exploratory work, individual differences may have influenced outcomes. But, overall, the current decision-making training and tDCS protocol appears unlikely to lead to benefits for older adults.

The relationship between social cognitive difficulties in the acute stages of stroke and later functional outcomes.

Although social cognitive difficulties are common following stroke, the extent to which such difficulties observed in the acute phase are related to long-term socioemotional outcomes remains poorly understood. To address this question empirically, 53 stroke patients completed a measure of Theory of Mind (The Reading the Mind in the Eyes Test) and a cognitive flexibility measure that has been related to social cognitive processes (a Reversal Learning Task) at hospital bedside. These participants then completed measures of socioemotional functioning at a 6-month follow-up. Baseline difficulties on the two measures were found to predict distinct types of socioemotional difficulties. The RMET uniquely predicted self-reported depression and loneliness whereas the Reversal Learning task uniquely predicted peer-reported social behavior, specifically social inappropriateness and stereotyping and prejudice. Importantly, a measure of general cognitive function did not explain variance in these outcome measures, suggesting that social cognitive difficulties are linked to poor socioemotional outcomes. By showing for the first time that social cognitive deficits observed acutely post-stroke are related to longer term functional outcomes, these findings reinforce the importance of including brief social cognitive measures as part of routine post-stroke clinical assessment.

Structural and functional brain correlates of theory of mind impairment post-stroke.

The ability to understand the mental states of others - also known as Theory of Mind (ToM) - is critical for normal social interactions. We combine behavioural probes with structural and functional brain imaging to provide the first comprehensive analysis of ToM deficits following stroke using the Reading the Mind in the Eyes Test (RMET). First, fMRI was used to identify the functional brain network involved in a non-clinical cohort. Results indicated that, relative to a control task, the RMET increased activity in a widespread functional bilateral network comprising frontal and temporo-parietal areas. To investigate how damage to grey and white matter components of this network can lead to ToM impairment, parcel-based lesion-symptom mapping (PLSM), white-matter tract-wise statistical analysis (TSA) and disconnectome symptom mapping (DSM) were performed using structural images from 64 stroke patients. PLSM results revealed that low scores on the RMET were associated with damage centered around the right posterior frontal gyrus and insula. TSA and DSM results further revealed that low RMET scores were associated with damage to white-matter tracts connecting frontal and temporo-parietal components of the RMET functional network. Together, these findings suggest that making judgements about the mental states of others imposes demands on a large functional network that can easily be disrupted, both by damage to grey matter areas that form part of the network directly, or the white-matter pathways that connect them.

Transcranial magnetic stimulation in obsessive-compulsive disorder: A focus on network mechanisms and state dependence.

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that has shown promise as an adjunct treatment for the symptoms of Obsessive-Compulsive Disorder (OCD). Establishing a clear clinical role for TMS in the treatment of OCD is contingent upon evidence of significant efficacy and reliability in reducing symptoms. Objectives: We present the basic principles supporting the effects of TMS on brain activity with a focus on network-based theories of brain function. We discuss the promises and pitfalls of this technique as a means of modulating brain activity and reducing OCD symptoms. Methods: Synthesis of trends and critical perspective on the potential benefits and limitations of TMS interventions in OCD. Findings: Our critical synthesis suggests the need to better quantify the role of TMS in a clinical setting. The context in which the stimulation is performed, the neural principles supporting the effects of local stimulation on brain networks, and the heterogeneity of neuroanatomy are often overlooked in the clinical application of TMS. The lack of consideration of these factors may partly explain the variable efficacy of TMS interventions for OCD symptoms. Conclusions: Results from existing clinical studies and emerging knowledge about the effects of TMS on brain networks are encouraging but also highlight the need for further research into the use of TMS as a means of selectively normalising OCD brain network dynamics and reducing related symptoms. The combination of neuroimaging, computational modelling, and behavioural protocols known to engage brain networks affected by OCD has the potential to improve the precision and therapeutic efficacy of TMS interventions. The efficacy of this multimodal approach remains, however, to be established and its effective translation in clinical contexts presents technical and implementation challenges. Addressing these practical, scientific and technical issues is required to assess whether OCD can take its place alongside major depressive disorder as an indication for the use of TMS.

Task instructions and implicit theory of mind.

It has been hypothesized that humans are able to track other's mental states efficiently and without being conscious of doing so using their implicit theory of mind (iToM) system. However, while iToM appears to operate unconsciously recent work suggests it does draw on executive attentional resources (Schneider, Lam, Bayliss, & Dux, 2012) bringing into question whether iToM is engaged efficiently. Here, we examined other aspects relating to automatic processing: The extent to which the operation of iToM is controllable and how it is influenced by behavioral intentions. This was implemented by assessing how task instructions affect eye-movement patterns in a Sally-Anne false-belief task. One group of subjects was given no task instructions (No Instructions), another overtly judged the location of a ball a protagonist interacted with (Ball Tracking) and a third indicated the location consistent with the actor's belief about the ball's location (Belief Tracking). Despite different task goals, all groups' eye-movement patterns were consistent with belief analysis, and the No Instructions and Ball Tracking groups reported no explicit mentalizing when debriefed. These findings represent definitive evidence that humans implicitly track the belief states of others in an uncontrollable and unintentional manner.

The influence of group membership and individual differences in psychopathy and perspective taking on neural responses when punishing and rewarding others.

Understanding how neural processes involved in punishing and rewarding others are altered by group membership and personality traits is critical in order to gain a better understanding of how socially important phenomena such as racial and group biases develop. Participants in an fMRI study (n = 48) gave rewards (money) or punishments (electroshocks) to in-group or out-group members. The results show that when participants rewarded others, greater activation was found in regions typically associated with receiving rewards such as the striatum and medial orbitofrontal cortex, bilaterally. Activation in those regions increased when participants rewarded in-group compared to out-group members. Punishment led to increased activation in regions typically associated with Theory of Mind including the medial prefrontal cortex and posterior superior temporal sulcus, as well as regions typically associated with perceiving others in pain such as the dorsal anterior cingulate cortex, anterior insula and lateral orbitofrontal cortex. Interestingly, in contrast to the findings regarding reward, activity in these regions was not moderated by whether the target of the punishment was an in- or out-group member. Additional regression analysis revealed that participants who have low perspective taking skills and higher levels of psychopathy showed less activation in the brain regions identified when punishing others, especially when they were out-group members. In sum, when an individual is personally responsible for delivering rewards and punishments to others, in-group bias is stronger for reward allocation than punishments, marking the first neuroscientific evidence of this dissociation.