From Immune Signaling to Social Cognition: Neuroimmune Contributions to Cognitive Dysfunction in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is characterized by persistent impairments in social communication together with restricted and repetitive patterns of behavior. Although ASD has traditionally been viewed primarily as a disorder of neural circuitry, increasing evidence indicates that interactions between the immune and nervous systems contribute substantially to brain development and cognitive function. This review develops a neuroimmune–cognitive–account of ASD by examining how immune signaling may influence neural organization and, in turn, cognitive function. Evidence from neuroimmunology, systems neuroscience, and experimental studies of neuromodulation is synthesized to examine relationships among immune signaling, neural network organization, and cognition. Disturbances in these processes have been associated with alterations in excitation–inhibition –balance and atypical large-scale connectivity, especially within networks supporting social cognition. We also examine the role of neuromodulatory systems, with particular emphasis on oxytocin and vasopressin, as intermediaries between biological regulation and cognitive processing. Experimental findings indicate that oxytocin can transiently modulate activity within social brain networks and increase the salience of socially relevant stimuli, although effects across clinical studies remain modest and inconsistent. The reviewed evidence suggests that disturbances in neuroimmune regulation may contribute to altered communication among distributed neural systems, providing one possible account of cognitive dysfunction in ASD. Social deficits, repetitive behaviors, and sensory differences reflect disturbances in the coordination of distributed neural systems rather than isolated impairments within single regions or pathways. This view has important implications for intervention, suggesting that approaches directed at individual molecular or neural targets alone are unlikely to produce broad or lasting effects. More effective strategies may require interventions that address interactions among immune function, neural dynamics, and cognitive processes. The resulting neuroimmune–cognitive account generates testable hypotheses concerning how immune processes may influence neural organization and cognition in ASD while providing a conceptual basis for future experimental and clinical research.