The relationship between functional brain connectivity and neuroinflammatory processes—new insights into the pathomechanisms of ASD

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Increasing evidence suggests that neuroinflammatory processes are closely associated with the pathophysiology of ASD, linking immune dysregulation with altered brain development and function. This review synthesizes current findings on the relationships between neuroinflammatory mechanisms, biochemical and metabolic alterations, and functional brain connectivity, as revealed by neuroimaging-particularly functional magnetic resonance imaging (fMRI). Across clinical, postmortem, and imaging studies, individuals with ASD show consistent evidence of microglial and astroglial activation, altered cytokine profiles (including IL-1β, IL-6, and TNF-α), and markers of oxidative stress such as glutathione imbalance and lipid peroxidation. These immune and metabolic alterations are associated with changes in synaptic plasticity, neurotransmission, and large-scale neuronal network organization, including altered functional connectivity within the default mode, salience, and executive control networks. Complementary imaging modalities further support links between glial activity, excitatory-inhibitory imbalance, and aberrant connectivity patterns. Emerging evidence also highlights interactions between inflammation, lipid metabolism, neurotransmitter systems (notably serotonin and dopamine), and genetic and epigenetic factors that modulate immune responses in ASD. Integrating inflammatory and metabolic biomarkers with fMRI and spectroscopic measures provides a promising framework for characterizing biologically informed ASD subtypes and advancing precision diagnostic and therapeutic strategies. Overall, current evidence supports a multilevel neuroimmune framework in which chronic inflammation and oxidative stress are associated with atypical functional brain connectivity in ASD. Future longitudinal and multimodal studies are required to validate candidate biomarkers, clarify mechanistic pathways, and evaluate interventions targeting neuroinflammatory processes.