UCLA

The integrity of human cognition relies on a delicate neural economy: the ability to efficiently gate sensory input and reserve attentional resources for the most salient environmental cues. In Autism Spectrum Disorder (ASD), this economy is calibrated distinctly, in most cases leading to Sensory Over-Responsivity (SOR) and atypical social engagement. This dissertation investigates the neural mechanisms underlying salience allocation in autism across three levels of analysis: task-based social-sensory integration, intrinsic network dynamics, and causal neuromodulation. Study 1 utilized functional MRI to examine how social relevance influences the processing of aversive sensory input. Results demonstrated that while typically developing youth show robust neural differentiation between social and nonsocial aversive stimuli, autistic youth exhibit reduced discrimination, responding primarily to the sensory intensity of the stimuli regardless of social context. Study 2 probed whether these patterns reflect stable neural traits or dynamic brain states using static functional connectivity and Co-Activation Pattern (CAP) analyses. Findings revealed that autistic youth possess heightened static coupling between the right anterior insula and sensory-thalamic regions, with spatiotemporal preferences for Salience Network (SN) coactivation with the executive control network. Findings from Study 2 suggest an intrinsic neural bias toward sensory processing and salience attribution processes at rest. Study 3 tested the modifiability of these circuits using repetitive Transcranial Magnetic Stimulation (rTMS) to the dorsolateral prefrontal cortex. Targeted intermittent theta-burst stimulation (iTBS) successfully reduced sensory-evoked neural activation and strengthened prefrontal-sensory regulatory connectivity, with the most pronounced effects observed in individuals with high SOR severity. Collectively, these studies point toward a unifying mechanism: atypical salience allocation, characterized by an over-prioritization of sensory noise at the expense of social relevance. This predisposition is driven by disrupted interactions between the salience network, sensory cortices, and prefrontal regulatory systems. Crucially, the discovery that these circuits are malleable through neuromodulation suggests that the sensory regulation mechanisms necessary for navigating a complex social world can be non-invasively reinforced, offering a promising path for clinical intervention.