Treating Civilian Traumatic Brain Injury With High Definition Transcranial Direct Current Stimulation (ciTBI-HDtDCS)

Using two treatment arms, the study will examine improvement of verbal retrieval and other cognitive deficits associated with remote traumatic brain injury by comparing (1) 1 milliamp transcranial direct current stimulation (tDCS) active treatment applied to presupplementary motor area for 20 minutes over 10 sessions to (2) sham tDCS following the same schedule. Additionally, after completing the initial active or sham treatment and 2-month follow-up testing sessions, participants will be invited back for newly assigned treatment conditions, 20 minutes over 10 sessions and will be re-evaluated at 2-months follow-up testing sessions.

Civilians with histories of traumatic brain injuries and observed cognitive deficits will be randomly assigned to one of the two treatment arms (and re-assigned for the second round of intervention, as described above). Primary outcome verbal retrieval measures, secondary neuropsychological and electroencephalography (EEG) measures, and prescreening assessments for study concussion history and contraindications for treatment will be collected prior to being assigned to a treatment arm (i.e., baseline). Magnetic resonance imaging of the brain will be obtained only at the baseline assessment.

Primary outcome verbal retrieval measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected after treatment session 10 and one time following treatment competition (i.e., 2-months). For participants who complete the second round of intervention, primary outcome verbal memory measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected again after treatment session 10 and one time following competition of the second treatment (i.e., 2-months).

This study was funded by NIH/NIDCD under grant number \[1K99DC020185\]. Federal funding concluded on 11/30/2024.

• Active Transcranial direct current stimulation (Device), also known as tDCS, 1 milliamp tDCS, High definition tDCS, High definition transcranial direct current stimulator, Neuroelectrics Starstim tES, SN E20200930-10: Transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. Stimulation will consist of 1 milliamp stimulation, with anodal stimulation delivered at electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, then remain at 1 milliamp of stimulation over 20 minutes, and finally ramping down at to 0 milliamps over 60 seconds.
• Sham Transcranial direct current stimulation (Device): Sham transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. The sham setup will consist of anodal electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, ramp down to 0 milliamps over 60 seconds and then be left off for 20 minutes.

Primary outcomes

• The Controlled Oral Word Association Test [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Control Word Association Test. Metric: Total Number of Correct Items Generated for three different letters. Total Range 0 (minimum) - 200 (maximum). Larger numbers indicate better performance.
• Category Fluency [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on Category Fluency. Metric: Total Number of Correct Items Generated for Animal. Total Range 0 (minimum) - 100 (maximum). Larger numbers indicate better performance.
• The Boston Naming Test [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on The Boston Naming Test - 30 items. Metric: Total Number of Correct Items Generated. Total Range 0 (minimum) - 30 (maximum). Larger numbers indicate better performance.
• Semantic Object Retrieval Test [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change in Semantic Object Retrieval Test. Metric: Total Number of Correct Retrievals. Total Range 0 (minimum) - 32 (maximum). Larger numbers indicate better performance.
• The Delis Kaplan Color Word Interference Test, Naming [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Delis Kaplan Color Word Interference Test. Metric: Time - seconds to Name Items. Total Range 0 (minimum) - 150 (maximum). Longer time indicates worse performance.
• The Delis Kaplan Color Word Interference Test, Reading [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Delis Kaplan Color Word Interference Test. Metric: Time - seconds to Name Items. Total Range 0 (minimum) - 150 (maximum). Longer time indicates worse performance.
• The Delis Kaplan Color Word Interference Test, Inhibition [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Delis Kaplan Color Word Interference Test. Metric: Time - seconds to Name Items. Total Range 0 (minimum) - 150 (maximum). Longer time indicates worse performance.
• The Delis Kaplan Color Word Interference Test, Inhibition and Switching [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Delis Kaplan Color Word Interference Test. Metric: Time - seconds to Name Items. Total Range 0 (minimum) - 240 (maximum). Longer time indicates worse performance.
• Rey Auditory Verbal Learning Test and Alternative Lists, Total Learning [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change in Rey Auditory Verbal Learning Test. Metric: Number of Total learning items and Correct Recalls. Total Range 0 (minimum) - 75 (maximum). Larger numbers indicate better performance.
• Rey Auditory Verbal Learning Test and Alternative Lists, Delayed Recall [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change in Rey Auditory Verbal Learning Test. Metric: Total Number of Delayed Recall items and Correct Recalls. Total Range 0 (minimum) - 15 (maximum). Larger numbers indicate better performance.

Secondary outcomes

• The Trail Making Test - Part A [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Trail Making Test (Parts A\&B). Metric: Time to Solution. Total Range 0 (minimum) - 300 (maximum). Longer time indicates worse performance.
• The Trail Making Test - Part B [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Trail Making Test (Parts A\&B). Metric: Time to Solution. Total Range 0 (minimum) - 300 (maximum). Longer time indicates worse performance.
• Digit Span Forward [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change in Digit Span Forward. Metric: Memory Span, a composite score of how many numbers are repeated correctly in a forward order. Z = 0 is the normed average, with positive Z values better and negative Z values worse than the normed average.
• Digit Span Backward [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change in Digit Span Backward. Metric: Memory Span, a composite score of how many numbers are repeated correctly in a backward order. Z = 0 is the normed average, with positive Z values better and negative Z values worse than the normed average.
• Rey-Osterrieth Complex Figure Test - Delayed Recall [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change in Rey-Osterrieth Complex Figure Test scores. Metric: Score. Total Range 0 (minimum) - 36 (maximum). This is a summed score of the number and accuracy of complex figure features captured. Larger numbers indicate better performance.
• The Digit Symbol Substitution Test [Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.]: Evaluation of treatment differences (active versus sham) in change on the Digit Symbol Substitution Test. Metric: Number of Items. Total Range 0 (minimum) - 135 (maximum). Larger numbers indicate better performance.

Sex: All, ages: 18 Years to 85 Years

Inclusion Criteria: Participants are to be between the ages of 18-85, are non-military personnel and not veterans, and have had a traumatic brain injury (more than a year ago prior to study participation) that has led to a complaint of word finding difficulty since the brain injury, confirmed to represent a verbal retrieval deficit based on neuropsychological testing criteria. Traumatic brain injury must be in the mild to moderate range based on evaluation, including the Ohio State TBI Identification Method (administered by our research group). You must be fluent in speaking and reading English.

Exclusion Criteria:

* an implanted/electronic device, such as a pacemaker, metallic cranial or intracranial implant (e.g., ventriculoperitoneal shunt), or a neurostimulator (e.g., vagus nerve stimulator, spinal stimulator, deep brain stimulator, etc.).
* skull defects
* a history of a psychological or neurological disorder, including, dementia of any type, epilepsy or other seizure disorders, post-traumatic stress disorder, brain tumor, present drug abuse, stroke, blood vessel abnormalities in the brain, Parkinson's disease, Huntington's disease, or multiple sclerosis.
* inability to give informed consent
* currently pregnant
* not a native English speaker

Participant flow

Outcome results

• The Controlled Oral Word Association Test (Primary), Mean, Total items: Active to Sham 30.67 +/- 7.23; Sham to Active 30.5 +/- 0.71
• Category Fluency (Primary), Mean, Total items: Active to Sham 18 +/- 1.73; Sham to Active 17 +/- 0
• The Boston Naming Test (Primary), Mean, Total items: Active to Sham 26.67 +/- 2.52; Sham to Active 28 +/- 0
• Semantic Object Retrieval Test (Primary), Mean, Total items: Active to Sham 30.33 +/- 1.53; Sham to Active 30.5 +/- 2.12
• The Delis Kaplan Color Word Interference Test, Naming (Primary), Mean, Time - seconds: Active to Sham 35.66666667 +/- 5.131601439; Sham to Active 41 +/- 7.071067812
• The Delis Kaplan Color Word Interference Test, Reading (Primary), Mean, Time - seconds: Active to Sham 26 +/- 6.244997998; Sham to Active 27.5 +/- 12.02081528
• The Trail Making Test - Part A (Secondary), Mean, Time - seconds: Active to Sham 37.66666667 +/- 14.36430762; Sham to Active 41.5 +/- 7.778174593
• The Trail Making Test - Part B (Secondary), Mean, Time - seconds: Active to Sham 68.66666667 +/- 21.57158625; Sham to Active 101 +/- 9.899494937
• Digit Span Forward (Secondary), Mean, Units on Z scale: Active to Sham 0.933333333 +/- 1.078579312; Sham to Active 0.4 +/- 0.707106781
• Digit Span Backward (Secondary), Mean, Units on Z scale: Active to Sham 0.2 +/- 1.252996409; Sham to Active 0.7 +/- 1.272792206
• The Delis Kaplan Color Word Interference Test, Inhibition (Primary), Mean, Time - seconds: Active to Sham 57 +/- 5; Sham to Active 71.5 +/- 9.192388155
• The Delis Kaplan Color Word Interference Test, Inhibition and Switching (Primary), Mean, Time - seconds: Active to Sham 71.33333333 +/- 19.85782801; Sham to Active 75 +/- 16.97056275
• Rey Auditory Verbal Learning Test and Alternative Lists, Total Learning (Primary), Mean, Total items: Active to Sham 40.66666667 +/- 15.14375559; Sham to Active 48.5 +/- 3.535533906
• Rey Auditory Verbal Learning Test and Alternative Lists, Delayed Recall (Primary), Mean, Total items: Active to Sham 7.333333333 +/- 5.033222957; Sham to Active 9.5 +/- 0.707106781
• Rey-Osterrieth Complex Figure Test - Delayed Recall (Secondary), Mean, Score on a scale: Active to Sham 15.16666667 +/- 0.577350269; Sham to Active 25.5 +/- 2.121320344
• The Digit Symbol Substitution Test (Secondary), Mean, Total items: Active to Sham 45 +/- 5.196152423; Sham to Active 45.5 +/- 14.8492424

Adverse events

Time frame: from enrollment until end of follow-up, up to 8 weeks

• Results publication: Adhikari. A., Devora, P., Vintila, T., Mathews, A., Nguyen, B., Motes, M., LoBue, C., Cullum, C.M., Hart, J., Chiang, H.-S., B - 36 Investigating High-Definition Transcranial Direct Current Stimulation for Remediating Word Finding Difficulty in Civilians with a History of Chronic Traumatic Brain Injury: a Pilot Study, Archives of Clinical Neuropsychology, Volume 39, Issue 7, October 2024, Page 1126

• Study Protocol and Statistical Analysis Plan (PDF, 2024-11-27)
• Informed Consent Form (PDF, 2024-11-27)

• John Hart, MD, Principal investigator, The University of Texas at Dallas

NIH grants: K99DC020185