ArticleResearch square2025
Transcranial Direct Current Stimulation in Older Adolescent with Chronic Mild Traumatic Brain Injury: A Case Study of Clinical and Functional Connectivity.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
This is the first case study, to our knowledge, to document pre- and post-tDCS resting-state functional MRI changes between the dorsolateral prefrontal cortex (DLPFC) and brainstem in an adolescent with chronic post-concussive symptoms following multiple mild traumatic brain injuries (mTBIs). By demonstrating that cortico-brainstem connectivity can be modulated through noninvasive neuromodulation, the novel findings of this case study attempt to inform mTBI treatment in adolescents exhibiting residual post-mTBI symptoms. A 19-year-old female with a history of three mTBIs (most recent five years prior) and persistent post-mTBI depression, anxiety, and post-concussive symptoms exhibited severe baseline hypoconnectivity between DLPFC and subcortical-brainstem nuclei, including the pontine reticular formation, raphe nuclei, and substantia nigra. Baseline behavioral testing revealed severe depressive and anxiety symptoms and elevated concussion symptom burden. The patient received transcranial direct current stimulation (tDCS; 1.5mA, 20 min, twice weekly for five weeks) with an anode over the left DLPFC and cathode over the contralateral supraorbital area. Post-intervention imaging revealed widespread polarity reversals and increased connectivity between DLPFC and brainstem arousal nuclei (e.g., periaqueductal gray, pontine reticular formation), alongside continued hypoconnectivity in serotonergic and dopaminergic nuclei. Clinically, depressive symptoms improved modestly, while anxiety and concussion symptom burden increased. This case demonstrates that adolescent mTBI can produce long-lasting disruption in prefrontal-brainstem networks and that tDCS may rapidly modulate these circuits in both restorative and deregulatory directions. Notably, neuromodulation may amplify arousal systems before stabilizing cortical control, underscoring the need for individualized montage design, close clinical monitoring, and longitudinal follow-up in post-mTBI rehabilitation.
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