No 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 subdivisions 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. SFA 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 presented as an early finding in patients with 22q11.2DS, contributing to impaired tolerance to stress.

The question of whether attention-related disorders such as attention-deficit/hyperactivity disorder (ADHD) are best understood as clinical categories or as extreme ends of a spectrum is an ongoing debate. Assessing individuals with varying degrees of attention problems and utilizing novel methodologies to assess relationships between attention and brain activity may provide key information to support the spectrum hypothesis. We scanned 91 neurotypical adolescents during rest using functional magnetic resonance imaging. We conducted static and dynamic functional network connectivity (FNC) analysis and correlated findings to behavioral metrics of ADHD, attention problems, and impulsivity. We found that dynamic FNC analysis detects significant differences in large-scale neural connectivity as a function of individual differences in attention and impulsivity that are obscured in static analysis. We show ADHD manifestations and attention problems are associated with diminished Salience Network-centered FNC and that ADHD manifestations and impulsivity are associated with prolonged periods of dynamically hyperconnected states. Importantly, our meta-state analysis results reveal a relationship between ADHD manifestations and exhibiting variable and volatile dynamic behavior such as changing meta-states more often and traveling over a greater dynamic range. These findings in non-clinical adolescents provide support for the continuum model of attention disorders.

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.

Objective: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. Methods: We used a word processing paradigm to assess neural activations in adults with ADHD ( N = 46) compared to controls ( N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD ( N = 18). Results: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. Conclusion: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.