Influence of High-Frequency Repetitive Transcranial Magnetic Stimulation on Neurobehavioral and Electrophysiology in Patients with Disorders of Consciousness

Abstract

Objective. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DOC). However, its therapeutic effects in the literature are inconsistently documented. The primary aim of this study was to explore the alterations in neural connectivity and neurobehavioral reactivity during rTMS modulation in patients with DOC. In addition, safety was investigated as a secondary aim. Methods. The presence of bilateral N20 components in DOC patients was determined by somatosensory-evoked potential (SEP) before enrollment in the study. A total of 64 patients were enrolled and randomly placed into the active and sham groups. Ultimately, 50 patients completed the study. Twenty-five patients in the active group underwent real HF-rTMS, and 25 patients in the sham group underwent sham HF-rTMS, which was delivered over the left dorsolateral prefrontal cortex (DLPFC). The outcome measures of performed pre- and postintervention included the latencies of the N20 and N20-P25 amplitudes of SEP, brainstem auditory-evoked potential (BAEP) grade, JFK Coma Recovery Scale-Revised (CRS-R) score, and Glasgow Coma Scale (GCS) score; any adverse events were recorded at any time during the intervention. Result. Following six weeks of treatment, a significant increase was observed in the total CRS-R and GCS scores, and the N20-P25 amplitudes of patients in the two groups were compared with that obtained from preintervention (all p values < 0.05). The waves of BAEP in the two groups also showed a trend toward normalized activity compared with preintervention grades ( p values < 0.05). A significant decrease in the latencies of N20 ( p values < 0.001) was observed in the active group compared with measurements obtained from preintervention, whereas no significant decrease was observed in the sham group ( p values = 0.013). The improvement in total CRS-R scores ( p values = 0.002), total GCS scores ( p values = 0.023), and N20-P25 amplitudes ( p values = 0.011) as well as the decrease in latencies of N20 ( p values = 0.018) and change in BAEP grades ( p values = 0.013) were significantly different between the two groups. The parameters in neural connectivity (N20-P25 amplitudes, N20 latencies, and BAEP grades) were significantly correlated with the total CRS-R and GCS scores at postintervention, and the changes of CRS-R before and after interventions have a positive relationship with N20-P25 amplitudes. No adverse events related to the rTMS protocol were recorded. Conclusion. Neural connectivity levels are affected by HF-rTMS and are significantly related to clinical responses in DOC patients with the presence of bilateral N20. The elevation of neural connectivity levels may lay a foundation for successful HF-rTMS treatment for DOC patients.

Effectiveness on level of consciousness of non-invasive neuromodulation therapy in patients with disorders of consciousness: a systematic review and meta-analysis

“…Results from assessment of bias using revised Cochrane risk-of-bias tool for parallel and cross-over studies were presented in Figures 2 , 3 . Only three studies were assessed as “low risks” (Peri et al, 2001 ; Chen et al, 2022 ; Fan et al, 2022 ). In addition, the majority of included studies ( n = 7) were assessed as “some concerns” because of indistinct illustration of randomization process or other relatively rare reasons (Cooper et al, 1999 ; Huang et al, 2017 ; Thibaut et al, 2017 ; Zhang et al, 2017 ; He et al, 2018 ; Martens et al, 2018 ; Wu et al, 2019 ).…”

Effect of high‐frequency repetitive transcranial magnetic stimulation over M1 for consciousness recovery after traumatic brain injury

“…In our recent study, it was found that using high-frequency rTMS to stimulate the injured part of the patient's affected side has a positive effect on the recovery of consciousness after TBI (Shen et al, 2019). In patients with effective treatment, it was found that the "motor" score in the CRS-R scale improved significantly, and the patient's prognosis was also better.…”

An update on noninvasive neuromodulation in the treatment of patients with prolonged disorders of consciousness

“…Similar to the choice of target in the protocol of tDCS, bilateral DLPFC and left M1 were also the most common targets in the TMS protocol. Six papers [39][40][41]44,45,49 reported its use in DLPFC, one session in left DLPFC 41 showed positive results only in the MCS group, and the other five (four in left DLPFC, 40,44,45,49 one in right DLPFC 39 ) all showed positive results in the real rTMS group. Two randomized sham-control trials selected M1 as the target.…”

“…Most of the past studies have used the CRS‐R scale as well as electrophysiological methods such as EEG, TMS‐EEG, brainstem auditory‐evoked potential (BAEP), and somatosensory‐evoked potential (SEP) to assess the effectiveness and changes in brain activity evoked by TMS 39,41,44,45,47,49 . In the last 5 years, electrophysiological methods have remained the primary means of assessment.…”

“… 38 Most of them were about 10 or 20 Hz. In the past 5 years, there were four articles about 10 Hz 39 , 40 , 41 , 42 , 43 , 44 and five articles about 20 Hz. 45 , 46 , 47 , 48 , 49 …”