Stable inhibition-related inferior frontal hypoactivation and fronto-limbic hyperconnectivity in obsessive–compulsive disorder after concentrated exposure therapy

Anders Lillevik Thorsen,Stella J De Wit,Pernille Hagland,Olga Therese Ousdal,Bjarne Hansen,Kristen Hagen,Gerd Kvale,Odile A Van Den Heuvel

doi:10.1016/j.nicl.2020.102460

Abstract

Response inhibition has previously been suggested as an endophenotype for obsessive–compulsive disorder (OCD), evidenced by studies showing worse task performance, and altered task-related activation and connectivity. However, it’s unclear if these measures change following treatment. In this study, 31 OCD patients and 28 healthy controls performed a stop signal task during 3 T functional magnetic resonance imaging before treatment, while 24 OCD patients and 17 healthy controls were rescanned one week and three months after concentrated exposure and response prevention over four consecutive days using Bergen 4-Day Format. To study changes over time we performed a longitudinal analysis on stop signal reaction time and task-related activation and amygdala connectivity during successful and failed inhibition. Results showed that there was no group difference in task performance. Before treatment, OCD patients compared to controls showed less inhibition-related activation in the right inferior frontal gyrus, and increased functional connectivity between the right amygdala and the right inferior frontal gyrus and pre-supplementary motor area. During error-processing, OCD patients versus controls showed less activation in the pre-SMA before treatment. These group differences did not change after treatment. Pre-treatment task performance, brain activation, and connectivity were unrelated to the degree of symptom improvement after treatment. In conclusion, inferior frontal gyrus hypoactivation and increased fronto-limbic connectivity are likely trait markers of OCD that remain after effective exposure therapy.

Highlights

Obsessive-compulsive disorder (OCD) is characterized by intrusive obsessions and repetitive compulsions (American Psychiatric Associa tion, 2013)
We recently found reduced connectivity between the fronto-parietal and limbic networks after treatment using resting-state functional magnetic resonance imaging (fMRI) (Thorsen et al, 2020), which may suggest that limbic and taskrelated areas become more independent after treatment
The baseline sample consisted of 31 OCD patients and 28 healthy controls, while 24 patients and 17 controls were included in longitudinal analyses including the day before treatment, after one week, and after three months (See Supplemental Fig. 1 for a flowchart with reasons for exclusions)

Summary

Introduction

Obsessive-compulsive disorder (OCD) is characterized by intrusive obsessions and repetitive compulsions (American Psychiatric Associa tion, 2013). The disorder affects 1–3% of the population, is related to substantial impairment in personal, family and work life, and often re mains chronic if untreated (Stein et al, 2019). OCD patients have difficulty stopping rituals or ruminating once they have started, and tasks measuring the ability to cancel behaviors may be relevant to study the neurobiological processes underlying these symp toms (van Velzen et al, 2014). Meta-analyses have shown that OCD patients show small to moderate difficulties in response inhibition relative to healthy controls, with the largest difference in action cancellation (Snyder et al, 2015)

Methods

Results

Conclusion