Impact of autism genetic risk on brain connectivity: a mechanism for the female protective effect.

The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains. To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8-17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder. The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls. These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.

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.

A Tablet-Based Assessment of Rhythmic Ability.

The exponential rise in use of mobile consumer electronics has presented a great potential for research to be conducted remotely, with participants numbering several orders of magnitude greater than a typical research paradigm. Here, we attempt to demonstrate the validity and reliability of using a consumer game-engine to create software presented on a mobile tablet to assess sensorimotor synchronization, a proxy of rhythmic ability. Our goal was to ascertain whether previously observed research results can be replicated, rather than assess whether a mobile tablet achieves comparable performance to a desktop computer. To achieve this, younger (aged 18-35 years) and older (aged 60-80 years) adult musicians and non-musicians were recruited to play a custom-designed sensorimotor synchronization assessment on a mobile tablet in a controlled laboratory environment. To assess reliability, participants performed the assessment twice, separated by a week, and an intra-class correlation coefficient (ICC) was calculated. Results supported the validity of this approach to assessing rhythmic abilities by replicating previously observed results. Specifically, musicians performed better than non-musicians, and younger adults performed better than older adults. Participants also performed best when the tempo was in the range of previously-identified preferred tempos, when the stimuli included both audio and visual information, and when synchronizing on-beat compared to off-beat or continuation (self-paced) synchronization. Additionally, high ICC values (>0.75) suggested excellent test-retest reliability. Together, these results support the notion that consumer electronics running software built with a game engine may serve as a valuable resource for remote, mobile-based data collection of rhythmic abilities.