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Habits are a powerful route to efficiency; the ability to constantly shift between goal-directed and habitual strategies, as well as integrate them into behavioral output, is key to optimal performance in everyday life. When such ability is impaired, it may lead to loss of control and to compulsive behavior. Habits have successfully been induced and investigated in rats using methods such as overtraining stimulus-response associations and outcome devaluation, respectively. However, such methods have ineffectively measured habits in humans because (1) human habits usually involve more complex sequences of actions than in rats and (2) of pragmatic impediments posed by the extensive time (weeks or even months), it may take for routine habits to develop. We present here a novel behavioral paradigm—a mobile-phone app methodology—for inducing and measuring habits in humans during their everyday schedule and environment. It assumes that practice is key to achieve automaticity and proficiency and that the use of a hierarchical sequence of actions is the best strategy for capturing the cognitive mechanisms involved in habit formation (including "chunking") and consolidation. The task is a gamified self-instructed and self-paced app on a mobile phone that enables subjects to learn and practice two sequences of finger movements, composed of chords and single presses. It involves a step-wise learning procedure in which subjects begin responding to a visual and auditory cued sequence by generating responses on the screen using four fingers. Such cues progressively disappear throughout 1 month of training, enabling the subject ultimately to master the motor skill involved. We present preliminary data for the acquisition of motor sequence learning in 29 healthy individuals, each trained over a month period. We demonstrate an asymptotic improvement in performance, as well as its automatic nature. We also report how people integrate the task into their daily routine, the development of motor precision throughout training, and the effect of intermittent reinforcement and reward extinction in habit preservation. The findings help to validate this "real world" app for measuring human habits. [ABSTRACT FROM AUTHOR]

Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder. [ABSTRACT FROM AUTHOR]

Background: Impulsivity and reward expectancy are commonly interrelated. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here, we assess human waiting impulsivity using a novel translational task, the 4-Choice Serial Reaction Time task, and the relationship with reward cues. Methods: Healthy volunteers (n = 29) performed the monetary incentive delay task as a functional MRI study where subjects observe a cue predicting reward (cue) and wait to respond for high (£5), low (£1), or no reward. Waiting impulsivity was tested with the 4-Choice Serial Reaction Time task. Results: For high reward prospects (£5, no reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial orbitofrontal cortex and lower supplementary motor area activity to cues. In response to high reward cues, greater waiting impulsivity was associated with greater subthalamic nucleus connectivity with orbitofrontal cortex and greater subgenual cingulate connectivity with anterior insula, but decreased connectivity with regions implicated in action selection and preparation. Conclusion: These findings highlight a shift towards regions implicated in reward valuation and a shift towards compulsivity away from higher level motor preparation and action selection and response. We highlight the role of reward sensitivity and impulsivity, mechanisms potentially linking human waiting impulsivity with incentive approach and compulsivity, theories highly relevant to disorders of addiction. [ABSTRACT FROM AUTHOR]

Background: Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim: We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods:We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n=20, with balanced left/right lesion sites). Results: Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion: The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation. [ABSTRACT FROM AUTHOR]

The compulsive behaviour underlying obsessive-compulsive disorder (OCD) may be related to abnormalities in decision-making. The inability to commit to ultimate decisions, for example, patients unable to decide whether their hands are sufficiently clean, may reflect failures in accumulating sufficient evidence before a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination, hypothesizing enhanced evidence accumulation relative to healthy volunteers. Twenty-eight OCD patients and thirty-five controls were tested with a low-level visual perceptual task (random-dot-motion task, RDMT) and two response conflict control tasks. Regression analysis across different motion coherence levels and Hierarchical Drift Diffusion Modelling (HDDM) were used to characterize response strategies between groups in the RDMT. Patients required more evidence under high uncertainty perceptual contexts, as indexed by longer response time and higher decision boundaries. HDDM, which defines a decision when accumulated noisy evidence reaches a decision boundary, further showed slower drift rate towards the decision boundary reflecting poorer quality of evidence entering the decision process in patients under low uncertainty. With monetary incentives emphasizing speed and penalty for slower responses, patients decreased the decision thresholds relative to controls, accumulating less evidence in low uncertainty. These findings were unrelated to visual perceptual deficits and response conflict. This study provides evidence for impaired decision-formation processes in OCD, with a differential influence of high and low uncertainty contexts on evidence accumulation (decision threshold) and on the quality of evidence gathered (drift rates). It further emphasizes that OCD patients are sensitive to monetary incentives heightening speed in the speed-accuracy tradeoff, improving evidence accumulation. [ABSTRACT FROM AUTHOR]

Compulsive sexual behaviour (CSB) is relatively common and has been associated with significant distress and psychosocial impairments. CSB has been conceptualized as either an impulse control disorder or a non-substance ‘behavioural’ addiction. Substance use disorders are commonly associated with attentional biases to drug cues which are believed to reflect processes of incentive salience. Here we assess male CSB subjects compared to age-matched male healthy controls using a dot probe task to assess attentional bias to sexually explicit cues. We show that compared to healthy volunteers, CSB subjects have enhanced attentional bias to explicit cues but not neutral cues particularly for early stimuli latency. Our findings suggest enhanced attentional bias to explicit cues possibly related to an early orienting attentional response. This finding dovetails with our recent observation that sexually explicit videos were associated with greater activity in a neural network similar to that observed in drug-cue-reactivity studies. Greater desire or wanting rather than liking was further associated with activity in this neural network. These studies together provide support for an incentive motivation theory of addiction underlying the aberrant response towards sexual cues in CSB. [ABSTRACT FROM AUTHOR]

Although compulsive sexual behaviour (CSB) has been conceptualized as a “behavioural” addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions. [ABSTRACT FROM AUTHOR]

Cortical interhemispheric interactions in motor control are still poorly understood and it is important to clarify how these depend on inhibitory/facilitatory limb movements and motor expertise, as reflected by limb dominance. Here we addressed this problem using functional magnetic resonance imaging (fMRI) and a task involving dominant/nondominant limb mobilization in the presence/absence of contralateral limb restraint. In this way we could modulate excitation/deactivation of the contralateral hemisphere. Blocks of arm elevation were alternated with absent/present restraint of the contralateral limb in 17 participants. We found the expected activation of contralateral sensorimotor cortex and ipsilateral cerebellum during arm elevation. In addition, only the dominant arm elevation (hold period) was accompanied by deactivation of ipsilateral sensorimotor cortex, irrespective of presence/absence of contralateral restraint, although the latter increased deactivation. In contrast, the nondominant limb yielded absent deactivation and reduced area of contralateral activation upon restriction. Our results provide evidence for a difference in cortical communication during motor control (action facilitation/inhibition), depending on the "expertise" of the hemisphere that controls action (dominant versus nondominant). These results have relevant implications for the development of facilitation/inhibition strategies in neurorehabilitation, namely, in stroke, given that fMRI deactivations have recently been shown to reflect decreases in neural responses. [ABSTRACT FROM AUTHOR]

This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool., Competing Interests: PB, MH, MG, MB, AM, TP, AS No competing interests declared, NF NAF in the past three years has received research funding paid to her institution from the NIHR, COST Action and Orchard. She has received payment for lectures from the Global Mental Health Academy and for expert advisory work on psychopharmacology from the Medicines and Healthcare Products Regulatory Agency and an honorarium from Elsevier for editorial work. She has additionally received financial support to attend meetings from the British Association for Psychopharmacology, European College for Neuropsychopharmacology, Royal College of Psychiatrists, International College for Neuropsychopharmacology, World Psychiatric Association, International Forum for Mood and Anxiety Disorders, American College for Neuropsychopharmacology. In the past she has received funding from various pharmaceutical companies for research into the role of SSRIs and other forms of medication as treatments for OCD and for giving lectures and attending scientific meetings, TR TWR discloses consultancy with Cambridge Cognition and receives research grants from Shionogi & Co. He also has editorial honoraria from Springer Verlag and Elsevier, (© 2023, Banca et al.)

Background: Compulsive checking, a common symptom of obsessive-compulsive disorder (OCD), has been difficult to capture experimentally. Therefore, determination of its neural basis remains challenging despite some evidence suggesting that it is linked to dysfunction of cingulostriatal systems. This study introduces a novel experimental paradigm to measure excessive checking and its neurochemical correlates., Methods: Thirty-one patients with OCD and 29 healthy volunteers performed a decision-making task requiring them to decide whether 2 perceptually similar visual representations were the same or different under a high-uncertainty condition without feedback. Both groups underwent 7T magnetic resonance spectroscopy scans on the same day. Correlations between out-of-scanner experimental measures of checking and the glutamate/GABA (gamma-aminobutyric acid) ratio in the anterior cingulate cortex, supplementary motor area, and occipital cortex were assessed. Their relationship with subjective ratings of doubt, anxiety, and confidence was also investigated., Results: Patients with OCD exhibited excessive and dysfunctional checking, which was significantly correlated with changes in the glutamate/GABA ratio within the anterior cingulate cortex. No behavioral/neurochemical relationships were evident for either the supplementary motor area or occipital cortex. The excessive checking observed in patients was negatively correlated with their confidence levels and positively related to doubt, anxiety, and compulsivity traits., Conclusions: We conclude that experimental measures of excessive and dysfunctional checking in OCD, which have been linked to increased doubt, anxiety, and lack of confidence, are related to an imbalance between excitatory and inhibitory neural activity within the anterior cingulate cortex. This study adds to our understanding of the role of this region in OCD by providing a laboratory model of the possible development of compulsive checking., (© 2023 The Authors.)

Obsessive-compulsive disorder (OCD) is characterised by structural and functional deficits in the cortico-striato-thalamic-cortical (CSTC) circuitry and abnormal neurochemical changes are thought to modulate these deficits. The hypothesis that an imbalanced concentration of the brain neurotransmitters, in particular glutamate (Glu) and gamma-amino-butyric acid (GABA), could impair the normal functioning of the CSTC, thus leading to OCD symptoms, has been tested in humans using magnetic resonance spectroscopy (MRS) and positron emission tomography (PET). This chapter summarises these neurochemical findings and represents an attempt to condense such scattered literature. We also discuss potential challenges in the field that may explain the inconsistent findings and suggest ways to overcome them. There is some convergent research from MRS pointing towards abnormalities in the brain concentration of neurometabolite markers of neuronal integrity, such as N-acetylaspartate (NAA) and choline (Cho). Lower NAA levels have been found in dorsal and rostral ACC of OCD patients (as compared to healthy volunteers), which increase after CBT and SSRI treatment, and higher Cho concentration has been reported in the thalamus of the OCD brain. However, findings for other neurometabolites are very inconsistent. Studies have reported abnormalities in the concentrations of creatine (Cr), GABA, glutamate (Glu), glutamine (Gln), Ins (myo-inositol), and serotonin (5-HT), but most of the results were not replicated. The question remains whether the NAA and Cho findings are genuinely the only neurochemical abnormalities in OCD or whether the lack of consistent findings for the other neurometabolites is caused by the lower magnetic field (1-3 Tesla (T)) used by the studies conducted so far, their small sample sizes or a lack of proper control for medication effects. To answer these questions and to further inform the biological underpinning of the symptoms and the cognitive problems at the basis of OCD we need better controlled studies using clear medicated vs unmedicated groups, larger sample sizes, stronger magnetic fields (e.g. at 7 T), and more consistency in the definition of the regions of interest., (© 2021. Springer Nature Switzerland AG.)

Vidal AC, Banca P, Pascoal AG, Cordeiro G, Sargento-Freitas J, Gouveia A and Castelo-Branco M. Bilateral versus ipsilesional corticosubcortical activity patterns in stroke show hemispheric dependence. Int J Stroke. Epub ahead of print 5 April 2018. DOI: https://doi.org/10.1177/1747493018767164. Ahead of Print article withdrawn by publisher. Due to an administrative error, this article was accidentally published Online First and in Volume 12 Issue 1 with different DOIs. Vidal AC, Banca P, Pascoal AG, Cordeiro G, Sargento-Freitas J, Gouveia A and Castelo-Branco M. Bilateral versus ipsilesional corticosubcortical activity patterns in stroke show hemispheric dependence. Int J Stroke. Epub ahead of print 5 April 2018. The correct and citable version of the article remains: Vidal AC, Banca P, Pascoal AG, Cordeiro G, Sargento-Freitas J, Gouveia A and Castelo-Branco M. Bilateral versus ipsilesional corticosubcortical activity patterns in stroke show hemispheric dependence. Int J Stroke 2017; 12(1): 71–83. DOI: https://doi.org/10.1177/1747493016672087.

There is recent evidence of deficits in praxis in patients with primary dystonia. Obsessive-compulsive disorder (OCD) has been linked to disorders of higher-order motor function, such as dystonia. However, no clear mechanism underlying such a relationship has been found. This pilot study aimed to identify whether patients with OCD might also show deficits in praxis. Patients with OCD were compared with healthy volunteers on a meaningless gesture imitation task. Patients showed significantly lower scores in this task. Further studies are needed to elucidate the nature of patients' deficits in praxis. This might reveal similar mechanisms underlying OCD and some types of movement disorders.

Objective: Current approaches in neurofeedback/brain-computer interface research often focus on identifying, on a subject-by-subject basis, the neural regions that are best suited for self-driven modulation. It is known that the hMT+/V5 complex, an early visual cortical region, is recruited during explicit and implicit motion imagery, in addition to real motion perception. This study tests the feasibility of training healthy volunteers to regulate the level of activation in their hMT+/V5 complex using real-time fMRI neurofeedback and visual motion imagery strategies., Approach: We functionally localized the hMT+/V5 complex to further use as a target region for neurofeedback. An uniform strategy based on motion imagery was used to guide subjects to neuromodulate hMT+/V5., Main Results: We found that 15/20 participants achieved successful neurofeedback. This modulation led to the recruitment of a specific network as further assessed by psychophysiological interaction analysis. This specific circuit, including hMT+/V5, putative V6 and medial cerebellum was activated for successful neurofeedback runs. The putamen and anterior insula were recruited for both successful and non-successful runs., Significance: Our findings indicate that hMT+/V5 is a region that can be modulated by focused imagery and that a specific cortico-cerebellar circuit is recruited during visual motion imagery leading to successful neurofeedback. These findings contribute to the debate on the relative potential of extrinsic (sensory) versus intrinsic (default-mode) brain regions in the clinical application of neurofeedback paradigms. This novel circuit might be a good target for future neurofeedback approaches that aim, for example, the training of focused attention in disorders such as ADHD.