Using a task that varied the monetary consequences of mistakes to examine how motivational factors modulate error-related neural processing, we have shown that OCD patients exhibit greater activity in VMPFC, due to a failure to deactivate this DMN region to the same extent as controls, both across all error types and specifically for errors associated with loss. Patients also showed more activation in aI/fO and altered functional connectivity between aI/fO and VMPFC, independent of event-related activation. By contrast, no differences were found between groups in pMFC regions associated with detection of cognitive conflict. We thus demonstrate alterations of function and connectivity in emotional/motivational brain systems in OCD, with evidence that these effects are not due to medication or history of depression. These data suggest that the enhanced error response in OCD may be due to an overvaluation of error significance potentially related to altered intrinsic connectivity between regions involved in valuation and emotion.
Previous research suggests that aI/fO, along with pMFC/dACC, is part of a network responding to salient external events (18
). Despite significant coactivation, these regions may have distinguishable functions (22
), with aI/fO being preferentially active in tasks involving autonomic-somatic responses and integration of bodily signals with “feeling states” (27
), such as risk (51
) and intolerance of uncertainty (52
). In the context of salience detection, then, aI/fO may respond to the perceived value of external events, in contrast to pMFC, which may be more engaged in processing cognitive information (21
) or the initiation of volitional behaviors when responding to salient events (23
). Right aI/fO in particular has been associated with sympathetic arousal (29
) and anticipation of aversive stimuli (26
). Our results suggest that OCD patients appraise the motivational salience of errors as greater than controls, with loss errors in particular eliciting activity in right aI/fO associated with arousal and negative emotion, consistent with our behavioral evidence indicating that OCD patients experienced errors as more frustrating than controls.
OCD patients also showed greater activity in VMPFC, a region of DMN that has been associated with a variety of motivational behaviors, including the experience of positive and negative emotions (45
), self-referential processing (56
), and risky decision-making (57
). Unlike pMFC and aI/fO, VMPFC tends to deactivate when attention is directed to external stimuli in cognitive tasks (31
), perhaps reflecting disengagement from or suppression of automatic internal emotional-evaluative processes (33
). Thus, OCD patients' reduced deactivation of VMPFC to errors may be due to an inability to properly disengage internal-evaluative processes when mistakes are detected.
This relative failure for OCD patients to deactivate VMPFC was seen not only across all errors, but also for errors involving a loss in excess of what was found for errors without consequences. Although the region of VMPFC found for loss > null errors was located posterior and ventral to the region emerging for all errors > corrects, areas within VMPFC are densely interconnected and strongly positively correlated (38
). Recently, however, it has been suggested that more posterior ventral regions of DMN are associated with projections of the self into the future (60
), suggesting that the posterior VMPFC activation found for loss errors in OCD may be related to greater concern for the future consequences of loss.
The notion of intrinsic functional connectivity has its roots in studies examining low frequency BOLD fluctuations during resting state (61
), yet has also been applied to connectivity analyses during task performance when variance associated with task events has been regressed out (47
). Using this latter method, we found that OCD was associated with greater positive coupling between VMPFC and right aI/fO than controls. Recent data suggests that aI/fO may be a central “hub” that initiates switching between central executive and default modes of processing (18
). If so, the significantly more positive relationship between aI/fO and VMPFC in OCD patients suggests that, in this disorder, activation of aI/fO is more likely to “switch on” internal-evaluative processes subserved by VMPFC, independent of task events. Although such interregional connectivity is independent of task events (or “spontaneous”) and linearly superimposed on event-related activations (48
), intrinsic coupling patterns may ultimately influence event-related responses, perhaps by maintaining the structural integrity and functional strength of network connections. Indeed, the fact that the amount of connectivity between VMPFC and right aI/fO in OCD patients was correlated with evoked responses in these areas during errors suggests that positive coupling within these regions is associated with an enhanced error-related response in OCD.
Although speculative, it is conceivable that altered activity in a system subserving salience detection and internal-emotional mentation could contribute to the OCD phenotype in several ways. In the simple case of a patient experiencing harm obsessions with checking compulsions, hyperactivity in neural regions detecting salience could lead to a greater attribution of the importance of various stimuli and associated safety behaviors (e.g., locking the door), while a concomitant inability to dampen internal-emotional responding may trigger fearful obsessions about negative outcomes resulting from mistakes in safety behaviors (e.g., an intruder entering through an unlocked door). Although it is unclear why certain stimuli appear to be more consistently over-valued than others, it may be evolutionarily adaptive to focus on safety-related items (62
Reduced VMPFC deactivation may not be specific to OCD (see ref 63
for review), having also been noted in major depression (64
), autism spectrum disorder (65
), and schizophrenia (66
), suggesting that an inability to disengage from evaluative and self-referential functions may be a general process that contributes to the pathophysiology of many disorders. It is perhaps the interaction of a VMPFC-based vulnerability with other brain regions, as well as the context in which VMPFC impairment is found (e.g., reduced VMPFC deactivation to errors in OCD vs. emotional faces in depression), that determines the clinical manifestation of VMPFC dysfunction.
While both OCD and control subjects showed error-related activation of pMFC, there were no group differences in this region. Although OCD patients exhibit an increased ERN, which has a source in pMFC (67
), there have been inconsistent results regarding the location of medial frontal increases in OCD, with one fMRI study finding differences only in VMPFC (12
), another only in pMFC (7
), and others in both regions (9
). The cause for these differences is unclear, but variability in sample sizes, tasks employed, and patient characteristics may be contributing to inconsistencies.
Limitations of the current study should be the focus of future research. Performance feedback provided on each trial was used to increase motivation, but made it impossible to disentangle neural activity to responses versus feedback. Although current interpretations are not dependent on distinguishing these events, future work may wish to examine OCD error responses in the absence of feedback to determine the generality of these findings. In addition, examination of resting state functional connectivity in OCD would complement the current findings of altered intrinsic connectivity during task, and help us further understand connectivity disturbances in the disorder. Despite these limitations, our results highlight the role of motivational brain systems in OCD, pointing to an overvaluation of errors related to alteration in functional relationships between networks processing external salience and emotional-evaluative internal thought.