Case Report: Anodal DLPFC-tDCS for refractory post-traumatic cognitive fatigue in the hypometabolic brain

Cognitive fatigue is among the most common and disabling long-term sequelae of mild traumatic brain injury (mTBI), with limited effective treatment options. We report a case of refractory post-mTBI cognitive fatigue treated with home-based anodal transcranial direct current stimulation (tDCS) guided by FDG-PET/MRI findings.

A patient sustained an mTBI in 2013 following a high-speed motorcycle accident, with possible loss of consciousness and approximately four hours of post-traumatic amnesia. Despite more than a decade of multidisciplinary rehabilitation, he remained unable to return to work due to severe cognitive fatigue (Fatigue Severity Scale [FSS-7] 5.4/7), post-traumatic headache, fatigue-exacerbated dysarthria, photophobia, phonophobia, and poor sleep (STOP-Bang score: 5, high risk for OSA). At the time of treatment, he was taking methylphenidate and galcanezumab. Pre-treatment FDG-PET/MRI demonstrated bilateral prefrontal hypometabolism (left greater than right) and parietal hypometabolism, with relative hypermetabolism in the left temporal lobe, anterior cingulate cortex, and brainstem. These findings informed selection of the left dorsolateral prefrontal cortex (DLPFC) as the stimulation target.

A 14-day home-based tDCS protocol was administered, with the first session completed in clinic. Stimulation was delivered at 2 mA for 20 min daily using an anode placed over F3 (left DLPFC) and cathode over F4 (right DLPFC), concurrent with structured cognitive exercises.

Following treatment, fatigue improved substantially (FSS-7: 5.4 to 3.7), exceeding the reported minimal clinically important difference. Modified Fatigue Impact Score (MFIS: 31 to 27), including the cognitive fatigue subscale (21 to 16). Cognitive performance also improved, with gains in processing speed (Symbol Digit Modalities Test: 46 to 58) and global cognition (Montreal Cognitive Assessment: 26 to 29). Measures of mood, anxiety, and quality of life remained stable. No serious adverse events were reported.

Home-based anodal tDCS targeting the left DLPFC was associated with clinically meaningful reductions in chronic post-mTBI cognitive fatigue and improvements in cognitive performance. This case highlights the potential utility of FDG-PET/MRI as a biomarker to guide personalized neuromodulation and supports further investigation of DLPFC-targeted tDCS for treatment-resistant post-traumatic fatigue.