Mitochondrial Dysfunction, Neural Network Dysregulation, and Precision QEEG
Guided Photobiomodulation in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a heterogeneous
neurodevelopmental condition characterized by impairments in social
communication, repetitive behaviors, sensory abnormalities, and atypical
cognitive functioning. Increasing evidence suggests that ASD involves complex
interactions among metabolic, neurophysiological, immunological, and
electrophysiological processes, with mitochondrial dysfunction emerging as a
potentially important contributor to altered cellular energy metabolism, oxidative
stress, neuroinflammation, atypical neural synchronization, disrupted functional
connectivity, and large-scale neural network dysregulation.
This chapter examines the relationships among mitochondrial
dysfunction, neural network dysregulation, and electrophysiological
abnormalities in ASD through the complementary frameworks of quantitative
electroencephalography (QEEG) and transcranial photobiomodulation (tPBM).
QEEG is reviewed as a non-invasive tool for evaluating cortical functioning,
oscillatory regulation, functional connectivity, and large-scale brain network
organization, while tPBM is explored as a neuromodulation modality that may
influence mitochondrial function, cellular bioenergetics, neuroplasticity, neural
synchronization, large-scale network organization, and cortical regulation
through stimulation of cytochrome c oxidase within the mitochondrial electron
transport chain.
By integrating findings from mitochondrial biology, neurophysiology,
network neuroscience, and neuromodulation research, this chapter highlights the
potential value of QEEG-guided tPBM as a biomarker-informed precision
neuromodulation approach for evaluation, individualized intervention planning,
and monitoring of neurophysiological change in ASD. Illustrative adolescent and
adult single case studies demonstrate how QEEG biomarkers may be used to
identify neurophysiological abnormalities in spectral power, coherence, phase-lag
dynamics, hemispheric asymmetry, and functional connectivity while monitoring
electrophysiological changes following intervention. Although preliminary
findings are encouraging, further controlled research is needed to establish
optimal stimulation parameters, clarify underlying biological mechanisms, and
determine long-term neurophysiological and clinical outcomes.