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The capacity to flexibly respond to contextual changes is crucial to adapting to a dynamic environment. Compulsivity, or behavioural inflexibility, consists of heterogeneous subtypes with overlapping yet discrete neural substrates. The subthalamic nucleus (STN) mediates the switch from automatic to controlled processing to slow, break or stop behaviour when necessary. Rodent STN lesions or inactivation are linked with perseveration or repetitive, compulsive responding. However, there are few studies examining the role of latent STN-centric neural networks and compulsive behaviour in healthy individuals. We therefore aimed to characterize the relationship between measures of compulsivity (goal-directed and habit learning, perseveration, and self-reported obsessive – compulsive symptoms) and the intrinsic resting state network of the STN. We scanned 77 healthy controls using a multi-echo resting state functional MRI sequence analyzed using independent components analysis (ME-ICA) with enhanced signal-to-noise ratio to examine small subcortical structures. Goal directed model-based behaviour was associated with higher connectivity of STN with medial orbitofrontal cortex (mOFC) and ventral striatum (VS) and more habitual model-free learning was associated with STN connectivity with hippocampus and dorsal anterior cingulate cortex (ACC). Perseveration was associated with reduced connectivity between STN and premotor cortex and finally, higher obsessive –compulsive inventory scores were associated with reduced STN connectivity with dorsolateral prefrontal cortex (PF). We highlight unique contributions of diffuse cortico-striatal functional connections with STN in dissociable measures of compulsivity. These findings are relevant to the development of potential biomarkers of treatment response in neurosurgical procedures targeting the STN for neurological and psychiatric disorders.

We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore–exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.

ObjectivesWaiting and stopping are essential and distinct elements of appropriate behavioural control with its dysfunction implicated in various impulsivity related mental disorders. Although rodent and human studies have investigated both phenomena, the role of preparing to stop in waiting impulsivity has rarely been investigated. Furthermore, convergent evidence from multi-modal investigation tools remains a poorly utilized approach in addressing such questions.MethodsHere, we conducted two separate, but hierarchical studies, using functional magnetic resonance imaging (fMRI) to map the neural circuit involved in waiting impulsivity and proactive stopping, and subsequently provide mechanistic and causal evidence of disruption of this circuit by transcranial magnetic stimulation (TMS). We used a validated human version of the 5-Choice Serial Reaction Time (5CSRT) task and developed a novel proactive stopping task.ResultsWe first show a shared neural network comprising the pre-supplementary motor area and bilateral anterior insula underlying both waiting impulsivity and proactive stopping. We further demonstrate activity in dorsomedial prefrontal cortex and left inferior frontal gyrus (LIFG) negatively correlated with waiting impulsivity in trials with additional target onset delay. A subsequent study applying continuous theta burst stimulation (a TMS inhibitory protocol) to LIFG in fifty-one healthy volunteers in a single-blind, randomized control-design, demonstrated active stimulation of LIFG significantly increased waiting impulsivity.ConclusionsOur findings highlight the relevance of task design in assessing waiting impulsivity with CSRT tasks and highlight the role of LIFG integrity and related neural circuitry in waiting impulsivity.

ObjectiveFunctional neurological disorder (FND) is characterised by unexplained neurological symptoms, including movement, seizures or sensory symptoms that are unrelated to an underlying neurological disorder. As FND presents as ∼16% cases in neurology clinics (Stone et al, 2010) and the current understanding of its aetiology is limited, research into the neural disturbances present in this group is critical. FND subjects have been shown to display enhanced amygdala activity to arousing stimuli (Voon et al, 2010), however delineation of the roles of each subnuclei have not yet been achieved. In this study, we examined the response of FND subjects to fear conditioning and their sensitivity to loss.Method25 FND and 20 healthy volunteers (HV) were conditioned to aversive/negative affective (CS+) or neutral (CS-) stimuli. During functional MRI, subjects performed a two-choice learning task to avoid monetary loss. The stimuli used in the two-choice task included the previously conditioned stimuli and were associated with a greater likelihood of a loss outcome.ResultsFND patients were more impaired at learning to avoid losses. Using reinforcement learning modelling, we show that FND subjects had a more negative valuation of the CS+ and greater noisy choice behaviours in the context of the CS+. Compared to HV, FND patients showed enhanced Centromedial amygdala responses to loss compared to neutral feedback in the context of the negative/aversive CS+, which correlated with greater impairments in avoidance learning.ConclusionThe findings show that although FND patients have enhanced sensitivity to negative outcomes, this fails to be adaptive, and is not used to guide avoidance learning. We show no evidence for greater harm avoidance but rather a generalised impairment in the capacity to use negative outcomes to guide behaviours. Furthermore, fearful learned contexts enhance the randomness of choice behaviours, thus highlighting a potential mechanism by which negative contexts interfere with adaptive behaviours. Our findings further detail the aetiology of a common but elusive disorder and highlight the potential utility of interventions targeting the salience of negative stimuli.