Mentalizing in Adolescents and Young Adults with Attention Deficit Hyperactivity Disorder: Associations with Age and Attention Problems.

INTRODUCTION: Growing, albeit heterogenous evidence questions whether attention deficit/hyperactivity disorder (ADHD) is associated with socio-cognitive impairments, especially beyond childhood. This study focuses on mentalizing - the socio-cognitive ability to attribute and reason in terms of mental states. We aimed to characterize mentalizing performance in terms of correct scores and types of errors in adolescents and young adults with ADHD. METHODS: Forty-nine adolescents and adults with ADHD and 49 healthy controls matched for age and gender completed a computerized naturalistic mentalizing task, the Movie for Assessment of Social Cognition (MASC). Repeated measures analyses of variance examined the effects of age group and ADHD diagnosis on MASC performance. Additionally, associations between mentalizing scores, the severity of attention problems, and the presence of comorbidity were explored in the ADHD group. RESULTS: Results showed an increased prevalence of hypomentalizing errors in adolescents with ADHD. Lower mentalizing scores in adolescents with ADHD were correlated with indices of inattentiveness, impulsivity, and vigilance problems. Hypomentalizing errors in adolescents showed to be particularly associated with inattentiveness, after controlling for age and comorbidity. In contrast, adults with ADHD performed similarly to controls and their scores on the mentalizing task were not correlated to attention problems. CONCLUSION: These findings highlight potential developmental differences in mentalizing abilities in ADHD youths and their association with attentional impairments.

Longitudinal Analysis of Brain Function-Structure Dependencies in 22q11.2DS and Psychotic Symptoms.

BACKGROUND: Understanding how brain function and structure relate to one another, compared to conventional unimodal analysis, opens a new biologically-relevant assessment of neural mechanisms. However, how function-structure dependencies evolve throughout typical and abnormal neurodevelopment remains elusive. The 22q11.2 deletion syndrome (22q11.2DS) offers an important opportunity to study the development of function-structure dependencies and their specific association to the pathophysiology of psychosis. METHODS: Previously, we used graph signal processing to combine brain activity and structural connectivity measures in adults, quantifying functional-structural dependency (FSD). Here, we combined FSD with longitudinal multivariate partial least squares correlation (PLS-C) to evaluate FSD alterations across groups and among patients with and without mild to moderate positive psychotic symptoms (PPS). We assessed 391 longitudinally repeated resting-state functional and diffusion-weighted magnetic resonance imaging from 194 healthy controls and 197 deletion carriers (age span 7-34, data collected over a span of 12 years) RESULTS: Relative to controls, patients with 22q11.2DS showed a persistent developmental offset from childhood, with regions of hyper- and hypo-coupling across the brain. Additionally, a second deviating developmental pattern showed an exacerbation during adolescence, presenting hypo-coupling in frontal and cingulate cortex and hyper-coupling in temporal regions for patients with 22q11.2DS. Interestingly, the observed aggravation during adolescence was strongly driven by the PPS+ group. CONCLUSIONS: These results confirm a central role of altered FSD-maturation in the emergence of psychotic symptoms in 22q11.2DS during adolescence. The FSD deviations precede the onset of psychotic episodes and thus offer a potential early indication for behavioral interventions in individuals at risk.

The continuum of attention dysfunction: Evidence from dynamic functional network connectivity analysis in neurotypical adolescents.

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.

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

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.

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

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.

Impact of couple conflict and mediation on how romantic partners are seen: An fMRI study.

Previous studies on romantic love have reported increased neural activity in the brain's reward circuitry such as the striatum. To date, the extent to which this activity is modulated by couple conflict in general and mediated couple conflict in particular, is unknown. The present study seeks to fill this gap by randomly assigning 36 romantic heterosexual couples to a mediated or non-mediated conflict discussion. Before and after the conflict discussion, self-reports and functional neuroimaging data in response to a picture of the romantic partner versus an unknown person were acquired. Self-reports indicate that mediation increases conflict resolution, satisfaction about the contents and process of the discussion and decreases levels of remaining disagreement. Pre-conflict neuroimaging results replicate previous studies on romantic love, showing activations in the striatum, insula, anterior and posterior cingulate gyrus, orbitofrontal cortex, hippocampus, temporal and occipital poles and amygdala when viewing the romantic partner versus an unknown person. The general effect of conflict on neural activations in response to the romantic partner across both conditions consisted of deactivations in the striatum, insula, thalamus, precuneus and ventral tegmental area. Small volume correction analyses revealed that participants in the mediated condition trended towards having greater activation in the nucleus accumbens than participants in the non-mediated condition when looking at the romantic partner versus the unknown after the conflict discussion. Parametric modulation analyses also revealed greater activity in the nucleus accumbens when viewing the romantic partner versus the unknown for participants who felt more satisfied after the conflict resolution. Our results illustrate that mediation improves conflict resolution and is associated with increased activity in the nucleus accumbens, a key region in the brain's reward circuitry.