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Title: The neural correlates of impaired cognitive control in Obsessive-Compulsive Disorder
Authors: Banca, Paula 
Orientador: Castelo-Branco, Miguel
Relvas, João
Voon, Valerie
Keywords: Distúrbio obsessivo compulsivo; Cognição; Tomada de decisão; Córtex pré-frontal; Putamen
Issue Date: 12-Feb-2015
Citation: BANCA, Paula Micaela de Oliveira - The neural correlates of impaired cognitive control in obsessive-compulsive disorder. Coimbra : [s.n.], 2014. Tese de doutoramento. Disponível na WWW em:<>
Abstract: Obsessive-compulsive disorder (OCD) is a very severe and lifelong psychiatric illness that is typically manifested by intrusive thoughts and compulsive urges to perform stereotypic and ritualistic behaviours. Patients experience these intense urges and compulsive actions despite having full insight into how senseless, irrational and excessive they are. This ego-dystonic nature of the disease is striking and has been an intriguing question for the scientific community. Compulsivity, a maladaptive perseveration of behaviour, arises from irrational decisions. Considering that decision-making is characterized by a parallel and flexible engagement between goal-directed and habitual systems, a recent account has suggested that a bias in favour of the latter might underlie compulsivity in OCD. In other words, compulsivity might result from excessive stimulus-response habit formation, rendering behaviour insensitive to goal value. The main focus of this thesis was the investigation of the mechanisms underlying compulsivity in OCD. We used a multimodal approach, combining standard behavioural, computational analysis and functional neuroimaging methods to provide an in-depth investigation of the decision-making abnormalities that may underlie the urge to perform compulsive acts. As compulsive acts may be conceptualized as a means to accumulate sufficient evidence for a decision’ commitment, the first study of this thesis investigated potential abnormalities in the cognitive process of weighing and evaluating evidence prior to a decision in OCD patients. This cognitive process is intrinsic to all decisions and is often abnormal in psychiatric disorders, varying from an impulsive to a cautious style of decision-making. We hypothesized that compared to healthy volunteers, OCD patients would need to accumulate more evidence, particularly under uncertainty situations. We indeed showed impairments in evidence accumulation processes for decisions of a perceptual nature in OCD, an impairment that was more evident in patients with higher compulsivity scores. We highlight the utility of behavioural, including computational, approaches by demonstrating a differential influence of high and low uncertainty contexts on evidence accumulation (decision threshold) and on the quality of evidence gathered (drift rates). Patients required more evidence under high uncertainty contexts. Nevertheless under low uncertainty ones, despite normative accumulation, the strength or quality of evidence from the stimulus entering the decision process was poorer compared to healthy volunteers. These findings suggest impaired decision-making processes in dissociated mechanisms underlying the encoding of perceptual uncertainty as function of its level. We further emphasize that OCD patients are sensitive to monetary incentives in heightening speed in the speed-accuracy tradeoff. In this manner, they improve evidence accumulation without sacrificing accuracy and shift away from a pathological internal monitoring. These results suggest a differential role of implicit incentives and external feedback in decision-making processes in OCD. In the second study of this thesis we developed 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 responses and to explore the recent habit account of OCD whereby compulsivity might arise from excessive avoidance habit formation. During symptom provocation, participants could choose to reject or terminate the provoking stimuli resulting in cessation of the provocation. This design allowed us to separately assess the neural correlates of symptom provocation, urge to avoid, rejection and relief. We identified a dichotomous pattern of activation/deactivation during exposure to symptoms characterized by a decreased activity of caudate-prefrontal circuits accompanied by hyperactivation of putaminal regions, suggesting a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in OCD. Effective connectivity analysis further allowed us to propose a causal model for compulsivity in OCD, in which two main structures causally influence the aforementioned corticostriatal dissociation: ventromedial prefrontal cortex and putamen. By suggesting an imbalance in circuitry underlying habitual and goal-directed action control as a fundamental mechanism underlying compulsivity in OCD, our findings and consequent proposed model provide a direct explanation for the impaired cognitive control observed in OCD patients as well as their ego-dystonic experience. Our results complement current models of symptom generation in OCD, corroborate the habit account of OCD and may enable the development of future therapeutic approaches that aim to alleviate this imbalance and suppress habits. The work presented in this thesis improves our knowledge concerning the mechanisms underlying compulsivity in OCD by demonstrating impaired decision-making and cognitive control in these patients. It further corroborates the recent habit based account of OCD and provides new insights on the neural basis of compulsive habits, explaining how they emerge and how they relate with the other core features of OCD: obsessions and anxiety.
Description: Tese de doutoramento em Programa de Doutoramento em Ciências da Saúde, ramo de Ciências Biomédicas, apresentada à Faculdade de Medicina da Universidade de Coimbra
Rights: embargoedAccess
Appears in Collections:FMUC Medicina - Teses de Doutoramento

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