Disease And Medication Effects On Emotional Processing In OCD: A Meta- And Mega-analysis Of Task-based FMRI Data Of The ENIGMA-OCD Consortium - Info and Reading Options

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Background Obsessive-compulsive disorder (OCD) patients have specific cognitive, emotional and behavioral dysfunctions that are both a consequence and a cause of altered brain structure and function. The ENIGMA consortium was founded to advance our understanding of the neurobiology of brain disorders (Thompson et al., 2020), including OCD, by using worldwide data. This is the largest OCD brain imaging consortium established to date, who’s combined sample includes thousands of OCD patients, both adult and pediatric, and healthy controls. Using structural MRI, diffusion MRI, and resting state functional MRI analyses, the ENIGMA-OCD consortium has already found that some OCD-related brain alterations may arise during neurodevelopment, while others are associated with duration of illness or medication use (van den Heuvel et al., 2022). Now the time has come to embark on a new phase of the ENIGMA-OCD consortium with a focus on OCD-related alterations in brain function during specific emotional and cognitive states. One functional domain known to be disrupted in OCD is emotional processing, subserved by the fronto-limbic circuit that encompasses the amygdala and ventromedial prefrontal cortex (consisting of ventral orbitofrontal cortex, subgenual anterior cingulate cortex, and the ventral part of the medial frontal gyrus) (Shephard et al., 2021). Across the ENIGMA-OCD consortium, various emotional tasks have been used to investigate the function of the fronto-limbic circuit in OCD during MRI, including the emotional Stroop task, the symptom provocation task, and the emotional faces task. Each of these tasks probes the domain in a different way, but it ultimately boils down to one basic contrast: emotional vs. neutral processing that we can use to study the functional differences between patients and controls across different tasks. Two meta-analyses have already compared OCD patients and healthy controls on emotional processing (Rotge et al., 2008; Thorsen et al., 2018), but these relied on coordinate-based meta-analytic methods using information from published results, that necessarily discard a large amount of information. Our approach pools individual participant fMRI data collected consortium-wide (both published and unpublished data) into an image-based mega-analysis, the first of its kind in OCD. The meta-analysis of Thorsen et al. (2018), based on 25 published studies, found that during emotional processing, OCD patients showed increased activation in the amygdala, OFC extending into the subgenual anterior cingulate and ventromedial prefrontal cortex, putamen, and middle temporal and inferior occipital regions, relative to healthy controls. Several patient factors were found to influence these results. Medication usage in the samples investigated was shown to correlate with activation in the right amygdala and left inferior occipital gyrus, indicating less hyperactivation of these areas in medicated as compared to unmedicated patients. Symptom severity was shown to correlate with activation in the subgenual and rostral ACC, and medial PFC. An effect of duration of illness was found, as samples with longer mean duration exhibited increased activation in the right putamen and decreased activation in the left temporal pole and orbitofrontal cortex. The smaller meta-analysis of Rotge et al. (2008), based on 8 published studies, found comparable differences between OCD patients and healthy controls in the OFC, ACC, temporal gyrus and anterior parts of the PFC, but also found increased activation in the medial PFC, globus pallidus, hippocampus, thalamus. These discordant results may be the product of reduced power and greater noise in the smaller meta-analysis. We use a newly-developed fMRI processing pipeline, ENIGMA HALFpipe, to harmonize preprocessing, first-level, and group-level analyses across sites (Waller et al., 2022). With the unprecedented power we now have to study disorder-related changes in neurobiology, we hope to validate previous findings in OCD, and to test how well they generalize to diverse populations worldwide.

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