Imbalance in habitual versus goal directed neural systems during symptom provocation in obsessive-compulsive disorder

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.

Keywords: caudate/putamen; causality; imbalanced circuitry; live symptom provocation; obsessive-compulsive disorder.

© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Experimental paradigm. (A) Examples of the two different modalities used for the symptom provocation task. (1) Online video-streaming of scenarios from the patients’ homes (remote provocation). Strong blocks were live videos capturing the experimenter disorganizing the patients’ homes while neutral videos showed the rooms as the patients had left them; (2) The tactile modality in which the experimenter directly delivered the provoking stimuli to the patient’s hand. In this case, the patient would see an image of a glove that she would touch. The visual presentation was intended to inform the patient about the type of stimuli delivered to the hand. (B) Contents of the stimulation block. Both modalities used a video-recording system to record and timestamp the exposure, decision to reject, rejection and relief events within the stimulation blocks. (C) Task timing. The experiment consisted of 30 s of provocation blocks of variable intensity (SB = stimulation blocks), 30 s of a baseline-counting task (DB = distractive baseline) and 6 s of response plus baseline block (R+B = response plus baseline). This sequence was repeated 12 times per run, for a total of four runs in each participant.

Figure 2

Between-group random effects general linear model analysis. Group × Provocation interaction for the strong > neutral provocation contrast. OCD patients showed greater bilateral putamen, globus pallidus, subthalamic nucleus, thalamus, dorsal ACC, insula, pre-supplementary motor area and substantia nigra relative to healthy controls and lower activity in ventromedial PFC, posterior cingulate and left dorsal caudate (P < 0.05, corrected for multiple comparisons using cluster threshold correction, minimum cluster size = 35 voxels). See Supplementary Table 2 for details regarding peak voxel coordinates, cluster size, t and P-values for random-effects analysis. COR = coronal; SAG = sagittal; RFX = random effects; TRA = transverse.

Figure 3

Random effects analysis at the event level in the OCD patient group. Hyperactivation of caudal dorsal cingulate cortex, amygdala, insula, putamen, globus pallidus and right caudate and deactivation of ventromedial prefrontal cortex. Peak deactivation coordinates (x,y,z): (SAG) left caudal dorsal cingulate cortex, BA 24, (−10,19,30), right caudal dorsal cingulate cortex, BA 24, (2,7,30); (TRA) right amygdala (23,−8,−9), left amygdala (−22,−3,−10), right ventromedial PFC/orbitofrontal cortex (8,52,−6), left ventromedial PFC/orbitofrontal cortex (−7,46,−6): (COR) left putamen (−19,−2,6), right putamen (23,1,2), right caudate (17,1,18), right palidum (12,1,6), left palidum (−16,−2,9), left insula (−34,19,9) right insula (31,13,18). Contrast: decision to reject + reject events > neutral condition, P < 0.05, corrected for multiple comparisons using cluster threshold correction, minimum cluster size = 104 voxels. COR = coronal; SAG = sagittal; RFX = random effects; TRA = transverse; A = anterior; P = posterior; L = left; R = right.

Figure 4

Analyses at the event level in the OCD patient group. (A) Left: Hyperactivation of bilateral putamen just before rejection events in the OCD patient group. Contrast: decision to reject > reject events, P < 0.05, corrected for multiple comparisons using cluster threshold correction, minimum cluster size = 17 voxels. Peak activation coordinates (x,y,z): left putamen (−19,4,0), right putamen (20,4,3). Right: Hypoactivation of bilateral putamen during stimulus withdrawal, P < 0.05, corrected for multiple comparisons using cluster threshold correction, minimum cluster size = 8 voxels. Peak activation coordinates: left putamen (−19,4,0), right putamen (20,4,3). (B) Estimated neuronal signal from the putamen (left and right) obtained by haemodynamic deconvolution of the blood oxygen level-dependent response. Zero represents the timing in which the rejection event started. (C) Activation of amygdala during relief periods. Peak activation coordinates: left amygdala (−25,1,−12) and right amygdala (17,−5,−9). Deactivation in bilateral caudate and putamen is not shown in this slice. Contrast: relief events > baseline, FFX general linear model, P < 0.05 FDR corrected, minimum cluster size = 103 voxels.

Figure 5

Connectivity analysis and causal model. (A) Connectivity analysis. Granger causality analysis shows that the head of the caudate (seed region from random effects general linear model analysis) is causally influenced by ventromedial prefrontal cortex (vmPFC) and that the caudal dorsal cingulate cortex (seed region for analysis) is influenced by the putamen. Putamen and amygdala seed region analyses are not shown in this figure but are referred to in the Results section. (B) Causal model inspired by integrating functional MRI and causality results: prefrontal structures (ventromedial prefrontal cortex) gate the modulation of basal ganglia (caudate and putamen) and limbic areas (amygdala). Putamen, by turn, a structure involved in repetitive and habitual behaviour, gates the activation of structures mediating action monitoring and repeated action patterns such as the caudal dorsal cingulate cortex and the presupplementary motor area (not shown). GCM = Granger Causality Modelling; RFX = random effects.