Transcranial Direct Current Stimulation for the Treatment of Deficits After Traumatic Brain Injury

Patients with mild-moderate traumatic brain injury (TBI) sustained between 3 months and 5 years ago with prolonged postconcussive symptoms will be recruited. On Day 1 of the study they will undergo neuropsychological (NP) testing. They will then undergo 10 days of Left dorsolateral prefrontal (DLPFC) anodal transcranial direct current stimulation (TDCS) (active or sham) combined with cognitive training. On day 10 NP testing will be obtained again. On Day 30, NP testing will be repeated a 3rd time. At 6 months and 1 year, quality of life, depression, and post concussive symptoms will be assessed.

Our long-term goal is to develop safe and effective treatments for symptoms of mild to moderate TBI (mmTBI) that restore patients to higher levels of functioning, decrease disability, and promote brain healing. The objective of this application is to investigate the use of transcranial direct current stimulation (tDCS) to treat symptoms of executive dysfunction and depression in patients with mmTBI. Our central hypotheses are (1) tDCS paired with relevant cognitive training facilitates improves executive function on National Institutes of Health (NIH)-approved neuropsychological measures, (2) tDCS reduces depression scores on NIH Common Data Elements for TBI, (3) that these improvements in emotion and cognition will be detectable up to one year after stimulation, and (4) certain clinical variables will reliably predict response to tDCS. These objectives were formulated based on our clinical experience with Dr. Ronald Yeo (project mentor) characterizing symptomatic patients with mmTBI in the post-acute setting and groundbreaking research led by Dr. Vincent Clark (project mentor) that has demonstrated robust increases in attention and learning with tDCS. Specific Aim 1: tDCS for executive dysfunction in mmTBI Experiments in this aim will test the hypothesis that in patients with mmTBI, left prefrontal anodal tDCS concurrent with cognitive training for ten consecutive weekdays will result in significantly more improvement in executive function compared to sham stimulation. Patients with cognitive complaints 3 months to 2 years after mmTBI will be recruited from local emergency departments and brain injury clinics. Aim 1.1: tDCS will be paired with computer-based cognitive training tasks of response inhibition, set shifting, and working memory, while executive function will be measured with the NIH Examiner battery before, immediately after, and one month after stimulation. Aim 1.2: Persistence of post-traumatic symptom reduction and quality of life improvement will be assessed with Common Data Elements instruments via telephone interview at 6 months and one year. Aim 1.3: Clinical predictors of tDCS response including injury severity, premorbid intelligence, and post-traumatic symptom burden will be determined with linear mixed-models analysis. Specific Aim 2: tDCS for depressive symptoms in mmTBI Experiments in this aim will test the hypothesis that left prefrontal anodal tDCS in patients with mmTBI will significantly reduce depressive symptoms compared to sham stimulation. Aim 2.1: Patients will be assessed for symptoms of depression via self-report instruments and clinician-administered scales from NIH Common Data Elements before, immediately after, and one month after the stimulation protocol. Aim 2.2: Persistence of antidepressant benefit will be assessed via telephone interview at 6 months and one year. Aim 2.3: clinical predictors of tDCS response such as injury severity, premorbid intelligence, and symptom burden will be determined.

traumatic brain injury, post concussive symptoms, depression, executive dysfunction, brain stimulation

In this arm, patients with mmTBI will undergo 10 sessions of active tDCS x 30 minutes combined with simultaneous cognitive training on consecutive weekdays.

In this arm, patients with mmTBI will undergo 10 sessions of placebo tDCS x 30 minutes combined with simultaneous cognitive training on consecutive weekdays.

Anodal tDCS lowers neuronal membrane potentials, leading to increased probability of depolarization from incoming stimuli.

The NIH Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) assesses executive function in four different domains, creating a composite score from all domains, ranging from -3.0 to 2.0 with higher scores indicating better outcome.

Inclusion Criteria: aged 18-55 TBI with + loss of consciousness (LOC) less than 24 hours injured between 3 months and 5 years ago Glasgow Coma Score (GCS) between 9 and 15 upon emergency department (ED) admission less than 1 week of post-traumatic amnesia (PTA) 1 out of 4 cognitive symptoms on the Neurobehavioral Symptom Inventory (NSI) Exclusion Criteria: history of neurological disease or seizures history of psychosis history of recent substance dependence (past 2 years) any skull defect presence of any implanted electrical device recent medical instability (within 3 weeks) pregnancy appointment of a legal representative.

Individual patient data on task performance may be requested from the researchers after study completion.