Using High Definition transcranial Direct Current Stimulation Guided by Electrophysiology and Diffusion Tensor Imaging to Treat Verbal Retrieval Deficits Secondary to Chronic Traumatic Brain Injury - PROJECT SUMMARY Language dysfunction is a common cognitive sequela of traumatic brain injury (TBI) in 31 % to 44% of TBI survivors. One of the most prevalent sequelae, word finding difficulty (verbal retrieval deficit), can persist more than 12 months after injury. Effective treatment and mechanism-based studies for such treatment, however, are still lacking. High-definition transcranial direct current stimulation (HD-tDCS) is a novel non-invasive electromodulation approach that has been shown to improve verbal retrieval deficits in TBI by targeting the pre-Supplementary Motor Area (pre-SMA). Disrupted synchronized activity involving the pre-SMA and impaired white matter connectivity linked to the pre-SMA can result in verbal retrieval deficits. Particularly, the left frontal aslant tract (FAT) and fronto-striatal tract (FST) support verbal retrieval function by connecting the pre-SMA to the left inferior frontal gyrus and basal ganglia, respectively. The 3 aims of this proposal are 1) to determine HD-tDCS modulatory effects on synchronized activity involving the pre-SMA using electroencephalography (EEG), 2) to use diffusion tensor imaging (DTI) to examine how baseline integrity of the left FAT and FST (as well as other white matter tracts central to speech and language function) affect pre-SMA HD-tDCS therapeutic effects, and 3) to establish predictive models of HD-tDCS induced changes by integrating baseline EEG and DTI measures. Both veterans and civilians with mild to moderate TBI will undergo ten 20-minunte sessions of active or sham HD-tDCS and will be evaluated immediately and at 8 weeks after treatment completion. The central hypothesis is that pre-SMA HD-tDCS will modulate pre-SMA associated synchronized activity to improve verbal retrieval, and that those effects will be predicated on the degree of disruption in baseline white matter integrity and synchronized activity. The expected results will offer a novel neurorehabilitation approach for verbal retrieval deficits across civilian and veteran TBI populations, along with clarification of underlying mechanisms, and provide a framework to guide future research and clinical application of electromodulation to treat TB I-related cognitive sequelae. This proposal is in line with the NIDCD's strategic plan under Voice, Speech, and Language Research including priority area 2 ( Identify the pathophysiologic and cognitive mechanisms underlying both common and rare voice, speech, and language impairments ) and priority area 3 ( Detection, Diagnosis and Hypothesis-Driven Interventions ). My proposed research will contribute to understanding verbal retrieval deficits in TBI and treating individuals affected by impaired communication due to such deficits. The R00 Award will support and establish my independent research career that will subsequently lead to independent funding through the NIH R01 mechanism or its equivalent by the end of the award period.
