Midbrain hypoactivation and mesocortical hypoconnectivity in inhibitory control learning in autism

Area of Science:

• Neuroscience
• Autism Spectrum Disorder Research
• Cognitive Neuroscience

Background:

• Repetitive behaviors are a core feature of autism spectrum disorder (ASD), often linked to impaired inhibitory control and error monitoring.
• The neural underpinnings of these deficits, particularly the role of subcortical structures, remain incompletely understood.
• A striatum-midbrain framework, incorporating dopaminergic signaling and actor-critic learning principles, offers a potential model for investigating response inhibition in ASD.

Purpose of the Study:

• To investigate the neural basis of response inhibition and its relation to repetitive behaviors in adults with ASD.
• To examine the functional roles of the striatum and midbrain in inhibitory control using a stop-signal task and functional MRI (fMRI).
• To explore differences in brain activation, functional connectivity, and learning dynamics between individuals with and without ASD.

Main Methods:

• Functional MRI (fMRI) was employed in 18 adults with ASD and 21 healthy controls performing a stop-signal task.
• Brain activation and functional connectivity were analyzed in the dorsal striatum and dopaminergic midbrain nuclei across task phases.
• Severity of repetitive behaviors was quantified using the Repetitive Behaviors Scale-Revised.

Main Results:

• Individuals with ASD exhibited significant midbrain hypoactivation during failed inhibition, correlating with the severity of repetitive behaviors.
• Reduced functional connectivity was observed in the ASD group between midbrain-striatum hubs and prefrontal cortex/insula during response preparation.
• Despite comparable final performance, autistic individuals showed slower learning and delayed striatal engagement when behavioral adjustments were needed.

Conclusions:

• Autism is characterized by midbrain hypoactivation and reduced long-range mesocortical hypoconnectivity, contributing to repetitive behaviors and impaired inhibitory control.
• These findings suggest midbrain-dependent reduced motivational arousal in ASD, hindering proactive learning strategies and behavioral regulation.
• The study highlights the critical role of dopaminergic midbrain structures in ASD, challenging solely cortical dysfunction views and suggesting targets for neurobiological interventions.