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1.
Brain ; 138(Pt 3): 798-811, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25567322

ABSTRACT

Intrusive thoughts and compulsive urges to perform stereotyped behaviours are typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a cognitive bias towards habit formation at the expense of goal-directed performance in obsessive-compulsive disorder. In this study, we test this hypothesis using a novel individualized ecologically valid symptom provocation design: a live provocation functional magnetic resonance imaging paradigm with synchronous video-recording of behavioural avoidance responses. By pairing symptom provocation with online avoidance responses on a trial-by-trial basis, we sought to investigate the neural mechanisms leading to the compulsive avoidance response. In keeping with the model of habit formation in obsessive-compulsive disorder, we hypothesized that this disorder would be associated with lower activity in regions implicated in goal-directed behaviours and higher activity in regions implicated in habitual behaviours. Fifteen patients with obsessive-compulsive disorder and 15 healthy control volunteers participated in this functional magnetic resonance imaging study. Online stimuli were individually tailored to achieve effective symptom provocation at neutral, intermediate and strong intensity levels. During the symptom provocation block, the participant could choose to reject or terminate the provoking stimuli resulting in cessation of the symptom provocation. We thus separately analysed the neural correlates of symptom provocation, the urge to avoid, rejection and relief. Strongly symptom-provoking conditions evoked a dichotomous pattern of deactivation/activation in patients, which was not observed either in control conditions or in healthy subjects: a deactivation of caudate-prefrontal circuits accompanied by hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during patients' symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in obsessive-compulsive disorder. Effective connectivity analysis identified the ventromedial prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry involved in the modulation of compulsivity in obsessive-compulsive disorder. These findings suggest an imbalance in circuitry underlying habitual and goal-directed action control, which may represent a fundamental mechanism underlying compulsivity in obsessive-compulsive disorder. Our results complement current models of symptom generation in obsessive-compulsive disorder and may enable the development of future therapeutic approaches that aim to alleviate this imbalance.


Subject(s)
Brain/pathology , Cognition Disorders/etiology , Goals , Obsessive-Compulsive Disorder/complications , Obsessive-Compulsive Disorder/pathology , Postural Balance/physiology , Sensation Disorders/etiology , Adult , Analysis of Variance , Brain/blood supply , Female , Humans , Linear Models , Magnetic Resonance Imaging , Male , Young Adult
2.
Article in English | MEDLINE | ID: mdl-24110693

ABSTRACT

Understanding the neurobiological mechanisms underlying different types of tremor and the altered functional connectivity of the involved areas is a timely goal in clinical neuroscience. If successful, this quest may open new perspectives on how to achieve tremor modulation, which is notably relevant, in Parkinson's disease (PD). Tremor can be characterized by simple parameters such as frequency and amplitude. It is therefore prone to be objectively targeted by neuromodulation and quantitatively investigated using multimodal techniques, such as, accelerometry, EMG and functional Magnetic Resonance Imaging (fMRI). Embarking on the latter challenge requires an a priori knowledge of how effective functional connectivity is altered in PD tremor. This works aims to ascertain which postural and voluntary movement tasks with distinct types of physical load are suitable for designing efficient fMRI protocols, by performing an accelerometry analysis to measure spontaneous and imposed tremor modulation on cohorts of PD patients, essential tremor patients and a group of voluntary healthy controls.


Subject(s)
Essential Tremor/physiopathology , Parkinson Disease/physiopathology , Tremor/physiopathology , Accelerometry , Aged , Aged, 80 and over , Case-Control Studies , Extremities/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Movement , Posture
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