These hypotheses could be tested in a number of ways. Re-analysis of existing datasets from treatment trials in OCD (pooled across individual studies, if necessary) that have included neuroimaging and/or neurocognitive measures could be conducted to examine whether the different neurocognitive dysfunctions and neurocircuit alterations discussed here predict better or worse response to our suggested neurocircuit-specific treatment options (e.g. do patients with fronto-limbic and ventral affective circuit dysfunctions respond better to SSRIs than those without?). For new studies, an important step will be to confirm the presence of the clinical profiles we propose. This could be achieved by content analyses of interviews in which patients describe their symptoms to confirm that dysregulated fear-like emotions, difficulties coping with uncertainty, sensory phenomena, a transition from obsession-driven compulsions to ritualistic habit-like behaviors, reward alterations and executive dysfunctions are valid themes under which patients can be grouped. Next, patients could be stratified based on their clinical profiles (e.g. sensory phenomena, dysregulated fear, excessive habit-formation), performance on neurocognitive tasks and underlying neural activity patterns in different neurocircuits and randomized to different treatment methods (e.g. dlPFC or pre-SMA tDCS/rTMS, amygdala fMRI-based neurofeedback, habit-reversal training) to assess whether treatments tailored to specific neurocircuits are more effective.
