Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS

Abstract

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision’s connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers. Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups. Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. Superficial amygdala hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms. Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was found to be an early finding in patients with 22q11.2DS, which contributes to impaired tolerance to stress.

Neural Basis of Internal Attention in Adults with Pure and Comorbid ADHD

“…To assess multivariate relationships between behavior and brain activations during internal and external attention, we ran a partial least squares correlation (PLS-C) analysis (Krishnan et al, 2011) in the ADHD all group. PLS-C is a well-established methodology used to assess brain-behavior relationships in various clinical populations (Delavari et al, 2022; Ziegler et al, 2013; Zöller et al, 2017) and we employed it using myPLS, a publicly available, Matlab-based toolbox (https://github.com/MIPLabCH/myPLS). To summarize the methodology used in PLS-C, we first computed correlations between matrix Y , which consisted of participants’ behavioral scores (ASRSi, ASRShi, and ALS), and matrix X , which consisted of voxel data per subject during the four task conditions (IntPos, IntNeg, ExtPos, ExtNeg).…”