Stern, E. R. | Search bioRxiv

bioRxiv2025

Inhibitory control and error processing in Obsessive-Compulsive Disorder: A mega-analysis of task-based fMRI data by the ENIGMA-OCD consortium

ObjectiveObsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to the maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult and pediatric data from the ENIGMA-OCD consortium and the ABCD study. MethodsIndividual participant data was uniformly processed using HALFpipe to extract statistical maps for response inhibition and error processing contrasts. Bayesian multilevel models were used to assess regional and whole-brain effects of OCD, with additional analyses examining the association between the OCD clinical profile and task-related activation. ResultsAcross inhibitory control tasks, both individuals with OCD and control participants showed robust activation in regions implicated in response inhibition and error processing. During response inhibition, compared to controls, adults with OCD showed stronger somatomotor cortex activation, while children with OCD showed stronger occipital cortex activation. Children with likely OCD from the ABCD cohort showed reduced activity in the frontoparietal network in the anterior insula/frontal operculum region. During error processing, relative to controls, adults with OCD showed weaker activation in fronto-striatal regions, while children with OCD showed stronger activation in frontoparietal and attention networks. Greater OCD symptom severity was associated with weaker task-related activation in adults and stronger activation in children during response inhibition. ConclusionCase-control differences in brain activation during inhibitory control varied by age group and task contrast. Symptom severity emerged as the main clinical correlate of activation during inhibition, suggesting that inhibitory control deficits in OCD may be both state-dependent and developmentally specific.

neuroscience↗

bioRxiv2024

Early Life Behavior Phenotypes and Cortisol Responses to Common Lab Stressors in a Cichlid Fish

The stress response is highly conserved across species, and increased glucocorticoid release (cortisol in fishes) is a key element. In the highly social cichlid fish, Burtons Mouthbrooder (Astatotilapia burtoni), stress axis activity is associated with juvenile social behavior and status, and it mediates early-life social effects, yet little is known about early-life stress physiology. We measured water-borne cortisol, a non-invasive method, in juveniles less than 1-week old. We first tested whether juveniles habituate to the beaker confinement necessary for sample collection. Repeated exposure to a beaker did not affect cortisol compared to handled and unhandled controls. In a separate cohort, we next measured behavior in an open field exploration and social cue investigation, followed by a test of whether common lab stressors elevated cortisol. Controls were undisturbed in a collection beaker (90 min). For the stressor treatments, we collected three sequential samples (30 min each) to try and quantify stress response peak and recovery; however, we found no effect of time. Stressors included handling, brief net confinement, and brief gentle movement. These stressors led to a significant increase in cortisol, with the highest levels resulting from confinement. The behavior tests revealed a bold-shy axis across both tests, describing the behavior of most individuals. A distinct group of socially-motivated juveniles showed a dramatic switch, staying in the territory during the open field but leaving to investigate the social cue. We found no associations between behavior and cortisol response. This work provides insight into early-life behavior and stress axis development and function. HighlightsO_LIAstatotilapia burtoni under 1-week old did not habituate to beaker confinement C_LIO_LIYoung juveniles displayed bold/shy or socially-motivated behavior phenotypes C_LIO_LICortisol increased in response to lab stressors: handling, confinement, and movement C_LIO_LIIndividual variation in cortisol establishes an expected hormone range for this age C_LIO_LIJuvenile cortisol did not correlate with behavior or differ by behavior phenotype C_LI

physiology↗