Sex Differences in Functional Connectivity of the Salience, Default Mode, and Central Executive Networks in Youth with ASD.

Autism spectrum disorder (ASD) is associated with the altered functional connectivity of 3 neurocognitive networks that are hypothesized to be central to the symptomatology of ASD: the salience network (SN), default mode network (DMN), and central executive network (CEN). Due to the considerably higher prevalence of ASD in males, however, previous studies examining these networks in ASD have used primarily male samples. It is thus unknown how these networks may be differentially impacted among females with ASD compared to males with ASD, and how such differences may compare to those observed in neurotypical individuals. Here, we investigated the functional connectivity of the SN, DMN, and CEN in a large, well-matched sample of girls and boys with and without ASD (169 youth, ages 8-17). Girls with ASD displayed greater functional connectivity between the DMN and CEN than boys with ASD, whereas typically developing girls and boys differed in SN functional connectivity only. Together, these results demonstrate that youth with ASD exhibit altered sex differences in these networks relative to what is observed in typical development, and highlight the importance of considering sex-related biological factors and participant sex when characterizing the neural mechanisms underlying ASD.

Differential patterns of amygdala and ventral striatum activation predict gender-specific changes in sexual risk behavior.

Although the initiation of sexual behavior is common among adolescents and young adults, some individuals express this behavior in a manner that significantly increases their risk for negative outcomes including sexually transmitted infections. Based on accumulating evidence, we have hypothesized that increased sexual risk behavior reflects, in part, an imbalance between neural circuits mediating approach and avoidance in particular as manifest by relatively increased ventral striatum (VS) activity and relatively decreased amygdala activity. Here, we test our hypothesis using data from seventy 18- to 22-year-old university students participating in the Duke Neurogenetics Study. We found a significant three-way interaction between amygdala activation, VS activation, and gender predicting changes in the number of sexual partners over time. Although relatively increased VS activation predicted greater increases in sexual partners for both men and women, the effect in men was contingent on the presence of relatively decreased amygdala activation and the effect in women was contingent on the presence of relatively increased amygdala activation. These findings suggest unique gender differences in how complex interactions between neural circuit function contributing to approach and avoidance may be expressed as sexual risk behavior in young adults. As such, our findings have the potential to inform the development of novel, gender-specific strategies that may be more effective at curtailing sexual risk behavior.

Cardiac implantable device outcomes and lead survival in adult congenital heart disease.

BACKGROUND: Long-term outcomes of cardiac implantable electronic devices (CIEDs) are ill-defined in adult congenital heart disease (ACHD). OBJECTIVE: To assess outcomes of transvenous (TV) and epicardial (EPI) CIEDs in ACHD. METHODS: A retrospective review of CIEDs implanted in patients >18 yrs. followed at the Ahmanson/UCLA ACHD Center was performed. Patients were grouped by implant approach. Primary outcomes included time to CIED dysfunction, lead dysfunction and unplanned CIED reintervention. RESULTS: Over a 27-year period, 283 CIEDs (208 TV, 75 EPI) were implanted in 260 ACHD patients. Dysfunction developed in 77 CIEDs (50 TV, 27 EPI) for which 62 underwent unplanned reintervention (47 TV, 15 EPI). Time to CIED dysfunction and unplanned reintervention did not differ by implant approach; however lead dysfunction was greater for EPI vs TV (HR 2.0, 95% CI 1.2-3.2, p = 0.01). Independent predictors of lead failure included cyanosis (HR 2.6, 95% CI 1.1-6.3; p = 0.03), implant indication other than bradycardia (HR 3.3, 95% CI 1.6-6.5; p < 0.01), right-sided Maze operation (HR 2.5, 95% CI 1.3-5.0; p = 0.01), and unipolar lead design (HR 4.5, 95% CI 1.8-11.5; p < 0.01). Importantly, EPI vs TV approach was not associated with lead dysfunction after adjusting for baseline covariates (HR 0.6, 95% CI 0.6-4.3; p = 0.3). CONCLUSION: Overall CIED system dysfunction and reinterventions are similar, whereas lead dysfunction is greater among EPI than TV devices. Patient and procedural differences, rather than EPI vs TV implant approach alone, appear to drive CIED lead outcomes in the ACHD population.

Sensory over-responsivity and social cognition in ASD: Effects of aversive sensory stimuli and attentional modulation on neural responses to social cues.

Sensory over-responsivity (SOR) is a common condition in autism spectrum disorders (ASD) that is associated with greater social impairment. However, the mechanisms through which sensory stimuli may affect social functioning are not well understood. This study used fMRI to examine brain activity while interpreting communicative intent in 15 high-functioning youth with ASD and 16 age- and IQ-matched typically-developing (TD) controls. Participants completed the task with and without a tactile sensory distracter, and with and without instructions directing their attention to relevant social cues. When completing the task in the presence of the sensory distracter, TD youth showed increased activity in auditory language and frontal regions whereas ASD youth showed decreased activation in these areas. Instructions mitigated this effect such that ASD youth did not decrease activation during tactile stimulation; instead, the ASD group showed increased medial prefrontal activity. SOR severity modulated the effect of the tactile stimulus on social processing. Results demonstrate for the first time a neural mechanism through which sensory stimuli cause disruption of social cognition, and that attentional modulation can restore neural processing of social cues through prefrontal regulation. Findings have implications for novel, integrative interventions that incorporate attentional directives to target both sensory and social symptoms.