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 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 TBI-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 inflicted by
impaired communication due to such deficits. The K99/R00 Career Development Award will allow me to
acquire data and advance training in cognitive neuropsychology, DTI analysis and predictive modeling in the
K99 phase. With this foundation, I will then establish my independent research in the R00 phase that will
subsequently lead to independent funding through the NIH R01 mechanism or its equivalent by the end of the
award period.
