Repetitive transcranial magnetic stimulation for improving cognition in veterans with TBI: Results from pilot clinical trial

Many returning OEF/OIF Veterans with concussion histories report cognitive problems that may last for months or even years. Co-morbid conditions such as post traumatic stress disorder (PTSD) and depression may prolong the symptoms of TBI resulting in lowered attention, processing speed, learning and memory. This study evaluated the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising therapeutic treatment for executive function (EF) deficits seen in mild to moderate Traumatic Brain Injury (TBI) Veterans. Thirty-Three Veterans with TBI (age 20-69 years; mild (n = 27) and moderate (n = 6) enrolled in either the treatment (n = 17) or the sham (n = 16) arm in a randomized clinical trial conducted at VA Palo Alto. The parameters currently FDA approved for Major Depressive Disorder (MDD) were utilized (Location: Left Dorsolateral Prefrontal cortex (DLPFC); Power: 120% of motor threshold; Pulse frequency: 10 Hz; Length of each pulse train: 5 seconds; Time between pulse trains: 10 seconds; Length of treatment: 20 mins; Total 4000 pulses/session, 5 days/week, 20 sessions). Preliminary analysis showed no difference between Sham and Active groups in one of the primary executive function change scores (Trails B; p > .1). Further analysis revealed an interaction with PTSD. Resting state fMRI analysis revealed a decrease in connectivity between stimulation site (LDLPFC) and cingulo-opercular network (CON) with a standardized beta effect size of -0.81 (p =.036) which was slightly associated with the digit coding task (p=0.046, beta=0.34). Biomarker data analysis further showed an increase in the ratio of BDNF/Pro-BDNF in Active vs. Sham groups from baseline to 10^th and 20^th treatment with the largest difference observed after 10^th treatment. These compelling results are preliminary and significant specifically in the neural and biochemistry mechanisms underlying the relationships between stimulation sites and networks heavily implicated in attention in this population.