Distinct Neural Correlates of Washing, Checking, and Hoarding SymptomDimensions in Obsessive-compulsive Disorder

Abstract

Context: Obsessive-compulsive disorder (OCD) is clinically heterogeneous, yet most previous functional neuroimaging studies grouped together patients with mixed symptoms, thus potentially reducing the power and obscuring the findings of such studies.Objective: To investigate the neural correlates of washing, checking, and hoarding symptom dimensions in OCD.Design: Symptom provocation paradigm, functional magnetic resonance imaging, block design, and nonparametric brain mapping analyses.Setting: University hospital.Participants: Sixteen patients with OCD (11 inpatients, 5 outpatients) with mixed symptoms and 17 healthy volunteers of both sexes.Intervention: All subjects participated in 4 functional magnetic resonance imaging experiments. They were scanned while viewing alternating blocks of emotional (washing-related, checking-related, hoarding-related, or aversive, symptom-unrelated) and neutral pictures, and imagining scenarios related to the content of each picture type.Main Outcome Measure: Blood oxygenation leveldependent response.Results: Both patients and control subjects experienced increased subjective anxiety during symptom provocation (patients significantly more so) and activated neural regions previously linked to OCD. Analyses of covariance, controlling for depression, showed a distinct pattern of activation associated with each symptom dimension. Patients demonstrated significantly greater activation than controls in bilateral ventromedial prefrontal regions and right caudate nucleus (washing); putamen/globus pallidus, thalamus, and dorsal cortical areas (checking); left precentral gyrus and right orbitofrontal cortex (hoarding); and left occipitotemporal regions (aversive, symptom-unrelated). These results were further supported by correlation analyses within patients, which showed highly specific positive associations between subjective anxiety, questionnaire scores, and neural response in each experiment. There were no consistently significant differences between patients with (n =9) and without (n=7) comorbid diagnoses. Conclusions:The findings suggest that different obsessive-compulsive symptom dimensions are mediated by relatively distinct components of frontostriatothalamic circuits implicated in cognitive and emotion processing. Obsessive-compulsive disorder may be best conceptualized as a spectrum of multiple, potentially overlapping syndromes rather than a unitary nosologic entity.

To discard or not to discard: the neural basis of hoarding symptoms in obsessive-compulsive disorder

“…None of the subjects had participated in our initial studies 13,15 but the same individuals took part in parallel experiments in our laboratory, which will be published separately.…”

“…17,28 Symptom provocation paradigm We used a paradigm that had reliably provoked OCD symptoms in previous studies by our group. 13,15,20 All subjects participated in two, 6-min fMRI experiments in which they viewed 10, 20-s alternating blocks of emotional and neutral pictures. The order in which the two experiments were conducted was fully counterbalanced, as was the order of the emotional and neutral conditions within each experiment.…”

“…In addition, across all OCD patients (n = 45), the severity of hoarding was negatively correlated with metabolism in the former region and positively correlated with metabolism in the latter region. Using functional magnetic resonance imaging (fMRI) and the abovementioned symptom provocation procedure, 13 Mataix-Cols et al 15 studied the neural correlates of hoarding symptoms in a consecutive sample of 16 OCD patients. Both patients and controls activated a similar network of brain regions in response to symptom provocation but, compared to healthy controls, OCD patients showed greater activation in left precentral (BA4/6) and fusiform (BA37) gyri, and in right orbitofrontal cortex (BA11).…”

“…18 These findings are consistent with the hypothesis of VMPFC involvement in compulsive hoarding and also agree with the clinical observations and questionnaire studies that have led Frost and colleagues 1,19 to postulate that difficulties in decisionmaking are landmark features of the 'compulsive hoarding syndrome '. This symptom provocation study builds upon previous work by our group 13,15 and aimed to examine the neural substrates of hoarding symptoms in OCD. To achieve this, we recruited new samples of OCD patients with (n = 13) and without (n = 16) prominent hoarding symptoms and healthy volunteers (n = 21) and studied their patterns of brain activity during the provocation of both hoarding-related and symptomunrelated anxiety using a previously validated symptom provocation paradigm.…”

“…To achieve this, we recruited new samples of OCD patients with (n = 13) and without (n = 16) prominent hoarding symptoms and healthy volunteers (n = 21) and studied their patterns of brain activity during the provocation of both hoarding-related and symptomunrelated anxiety using a previously validated symptom provocation paradigm. 13,15,20 Based on previous animal and human lesion studies, and the above functional neuroimaging and neuropsychological studies, we hypothesized that compared with healthy controls and non-hoarding OCD patients, OCD hoarders would show greater subjective anxiety, greater activation in VMPFC and limbic regions 13,15 and reduced activation in dorsal prefrontal regions 14 during symptom provocation. We also predicted that the three groups would show comparable subjective anxiety and neural responses during the generally aversive control experiment.…”