Task-based functional connectivity in striato-motor-cortical system in autism: Associations with sex and executive...

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Autism Spectrum Disorder Research

Background:

• Previous research identified reduced dorsal striatum (putamen) brain response in female autistic youth (Aut-F) viewing human motion.
• Larger rare copy number variants, including genes in early striatal development, were also noted in Aut-F.
• Striatal differences in Aut-F warrant further investigation into systems-level and behavioral implications.

Purpose of the Study:

• To analyze functional connectivity between the putamen and frontal targets in Aut-F compared to non-autistic females (NAut-F).
• To investigate sex differences in putamen-frontal connectivity.
• To determine which brain connectivity and phenotypic features predict executive function in youth.

Main Methods:

• Secondary data analysis of a sex-balanced cohort (ages 8-17).
• Psychophysiological interaction (PPI) analysis (N=184) to assess functional connectivity.
• Best subsets regression (N=200) to identify predictors of executive function.

Main Results:

• Aut-F (n=45) exhibited reduced functional connectivity between the left anterior putamen (Pa) and the dorsal premotor cortex/pre-supplementary motor area compared to NAut-F (n=45).
• This suggests diminished engagement of a key Pa-frontal pathway for attentional regulation in Aut-F.
• Left Pa-left dorsolateral prefrontal functional connectivity significantly predicted executive functioning variance across all participants, irrespective of neurotype.

Conclusions:

• Striatal differences in Aut-F may have adaptive consequences, partly due to altered connectivity with frontal regions crucial for attentional control.
• Findings highlight the role of Pa-frontal pathways in executive function and their potential differences in autistic females.
• This research contributes to understanding the neurobiological underpinnings of executive function differences in autism.