Neuromodulation for psychological sequelae of traumatic brain injury

Traumatic brain injury (TBI) frequently precipitates chronic psychological disorder, particularly anxiety, depression, post-traumatic stress disorder (PTSD), and increased suicide risk, that worsen with injury severity yet remain understudied relative to sensorimotor and cognitive deficits. As TBI severity increases, conventional interventions (pharmacotherapy, cognitive-behavioral therapy, exercise) lose efficacy, revealing an urgent need for novel treatments targeting affective and stress-related disorders. Neuromodulatory approaches such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), photobiomodulation (PBM), vagus nerve stimulation (VNS) and trigeminal nerve stimulation (TNS), offer a mechanism-based strategy to recalibrate dysfunctional neural circuits across the full spectrum of TBI severity. In this review, we present the first comprehensive review of 45 preclinical and clinical studies examining all six modalities in TBI. We delineate intervention-specific mechanisms encompassing enhancement of synaptic plasticity, restoration of large-scale network connectivity, normalization of neurotransmitter homeostasis, augmentation of cerebral perfusion, and attenuation of neuroinflammatory cascades, correlating these neurobiological changes with quantifiable improvements in affective symptoms and stress adaptation. Through rigorous mechanistic-to-clinical mapping, this analysis establishes an evidence-based framework for developing precision neuromodulation protocols and mechanism-targeted pharmacological interventions targeting TBI-associated psychological disorders.