Louise-Bender Pape et al. report an electrographic seizure with no clinical accompaniment in a patient in a vegetative state following 21 sessions of rTMS. The patient was a 32-year-old male who had suffered a TBI 9 years prior and had a GCS score of 6 at injury. Head CT prior to treatment revealed "multicystic encephalomalacia of almost the entire right cerebral hemisphere and most of the basal ganglia as well as hypoattenuation in the anterior frontal lobe and dilatation of third and lateral ventricles." Stimulation was applied using a paired-pulse technique with two 100 mus pulses applied at an interval of 100 ms, followed by 5 s of rest. Daily sessions of 300 pulses at 110% MT were administered over the left DLPFC. Neural activity was monitored using daily EEG recordings pre- and post-rTMS. Prior to the seizure, EEGs showed no evidence of epileptiform discharges or periodic complexes, but the authors note the presence of some neurophysiological disturbances indicated by slow wave abnormalities in the right central-parietal, right temporal, and left temporal areas. The electrographic activity originated in the right central-parietal region and extended to the mid-central and right temporal areas. The event lasted longer than 90 s, but stopped without medication. Subsequent EEGs were no different from recordings taken prior to the seizure. The patient was placed on 1000 mg levetiracetam and monitored carefully for a week. rTMS treatments were then resumed at 2% lower stimulation intensity and with 100 fewer pulses per session for an additional 19 sessions. No further adverse events were reported. The authors note that this rTMS-triggered seizure is unusual as it originated contralateral to site of stimulation.
In a double-blind cross-over study (N = 9), Kang et al. reported immediate but not lasting improvement in the attention of patients with TBI following a single tDCS session. MRI and anatomical CT scans demonstrated no significant brain atrophy or implants prior to intervention. Patients with a history of seizure or co-morbid medical/neurological conditions were excluded, and medication was kept constant throughout treatment. A single session of tDCS was administered with the anode over the left DLPFC (2 mA/25 cm2 x 20 min; sham 1 min on/19 min off) and the cathode over the contralateral supraorbital region. Attention was measured using a mini-mental status exam (MMSE) and computerized contrast reaction time task (CCRTT). The treatment group demonstrated improved attention from baseline compared to sham at 1-h follow-up but no significant differences were observed at 3 and 24 h post-treatment.
In a randomized double-blind controlled pilot study, Lesniak et al. found that repeated applications of tDCS in addition to daily rehabilitative cognitive training did not enhance attention or memory in patients with severe TBI. The study consisted of patients (N = 23) aged 18-45 who had experienced a TBI a minimum of 4 months prior to the study accompanied by loss of consciousness and/or post-traumatic amnesia, and no prior history of neurological/psychiatric conditions, post-injury seizures, or skull fractures/implants in the area of stimulation. Sham and treatment groups were randomized and matched by age, time since TBI, and severity of symptoms. Fifteen sessions of tDCS with the anode over the left DLPFC (1 mA/35 cm2 x 10 min, decreased intensity at start and finish; sham 25 s on/9.75 min off) and the cathode over the right supraorbital area were administered. Treatment was reported to be well tolerated with minor side effects. Fifteen computerized cognitive training sessions to improve memory were administered following tDCS intervention. Large effect sizes for treatment and sham group were reported but no statistically significant difference between the two groups was found.
Ulam et al. used a randomized, double-blind design to test the effect of repeated sessions of anodal tDCS on EEG oscillations and neuropsychological tests (attention, working memory, inhibitory control, cognitive flexibility, immediate and delayed memory for verbal and visual-spatial material, and emotion recognition) in patients with TBI. 23 patients (13 active tDCS and 13 sham) received anodal tDCS to the left PFC (1 mA/25 cm2 x 20 min) with the cathode over the right supraorbital area. EEG immediately after one session of tDCS demonstrated increased cortical excitability at the location of the anode. This increased excitability continued to be present 1 day following the 10th session, but was no longer restricted to the anodal location. There was no significant difference between the active and sham groups in their performance change on the neuropsychological tests, though both groups showed an overall improvement. However, there was a significant correlation between change in cortical excitability and neuropsychological improvement in the active group but not the sham group. Additionally, individuals in the active group who showed a greater slowing in EEG prior to tDCS intervention improved on a greater number of neuropsychological tests than did the rest of the active tDCS group.
Middleton et al. report the use of tDCS in conjunction with upper extremity physical therapy for patients with motor impairments resulting for stroke and/or TBI (N = 5, one with TBI, one with TBI + stroke). Bihemispheric tDCS was delivered with the anode over the ipsilesional motor cortex (1.5 mA/25 cm2 x 15 min) and cathode over the contralesional motor cortex, three times a week for 24 sessions, during strengthening and functional activities. Both TBI patients showed improvement on the Fugl-Meyer Assessment of Sensorimotor Impairment UE section (UE-FM), which assesses reflexes, range of motion, pain, light touch sensation, proprioception, movements in and out of synergy, grasp, and coordination. This improvement persisted at a 6-month follow-up. Performance changes in robotic reach and object-hit tasks were less consistent. No adverse effects of tDCS were reported. This small proof-of-concept study showed that tDCS was well tolerated by patients and can be incorporated into physical training without being a hindrance.