Cognitive sequences in obsessive-compulsive disorder are supported by frontal cortex ramping activity and mediated by symptom severity.

Completing sequences is part of everyday life. Many such sequences can be considered abstract - that is, defined by a rule that governs the order but not the identity of individual steps (e.g., getting dressed for work). Over-engagement in ritualistic and repetitive behaviors seen in obsessive-compulsive disorder (OCD) suggests that abstract sequences may be disrupted in this disorder. Previous work has shown the necessity of the rostrolateral prefrontal cortex (RLPFC) for abstract sequence processing and that neural activity increases (ramps) in this region across sequences (Desrochers et al., 2015, 2019). Neurobiological models of the cortico-striatal-thalamo-cortical (CSTC) loops describe prefrontal circuitry connected to RLPFC and that is believed to be dysfunctional in OCD. As a potential extension of these models, we hypothesized that neural dynamics of RLPFC could be disrupted in OCD during abstract sequence engagement. We found that neural dynamics in RLPFC did not differ between OCD and healthy controls (HCs), but that increased ramping in pregenual anterior cingulate cortex (rACC), and superior frontal sulcus (SFS) dissociates these two groups in an abstract sequence paradigm. Further, we found that anxiety and depressive symptoms mediated the relationship between observed neural activity and behavioral differences observed in the task. This study highlights the importance of investigating ramping as a relevant neural dynamic during sequences and suggests expansion of current neurobiological models to include regions that support sequential behavior in OCD. Further, our results may point to novel regions to consider for neuromodulatory treatments of OCD in the future.