Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study

Abstract

BackgroundRecent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied.MethodWe conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention.ResultrTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study.ConclusionsThis study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT05187000.

Research Progress of Different Modes of Transcranial Magnetic Stimulation in Patients with Consciousness Disturbance

“…According to information aggregation theory, the posterior parietal cortex (PPC) has been shown to be the largest cortical region associated with consciousness [18]. Xu et al [19] performed 10 Hz rTMS on the left PPC of 24 VS patients and found that it could significantly improve the functional recovery of unresponsive DoC patients. The precuneus is part of the posterior parietal cortex and is located in the BA7 region [20,21].…”

Behavioral Effects of Repetitive Transcranial Magnetic Stimulation in Disorders of Consciousness: A Systematic Review and Meta-Analysis

“…Three levels of bias risk (high, low, and unclear) were applied to grade the included studies. The articles included three high-quality studies with a low-level bias risk [27][28][29], two studies with a high level of bias risk [30,31], and three with a moderate risk of bias [24][25][26]. The risk of bias is shown in Figure 2.…”

“…Some studies reported that rTMS over the M1 could affect other brain regions and remedy patients with DoC [23][24][25][26]. A recent study showed that rTMS can be used over the posterior parietal cortex (PPC) to treat patients with DoC; however, the effectiveness requires further studies [27].…”

A protocol for a multicenter randomized and personalized controlled trial using rTMS in patients with disorders of consciousness

“…Thus, it is now established that TMS holds an important role in promoting and monitoring functional recovery in severe brain injury (10). In the field of DoC, some studies have investigated rTMS-induced changes on behavior (11) and electrophysiology (12) or both in patients with severe brain damage (12)(13)(14)(15)(16)(17). However, these protocols usually differ in several experimental parameters (e.g., stimulation site, stimulation intensity, number of sessions delivered), making it difficult to draw any conclusion on an effective stimulation protocol at this stage.…”

“…Eventually, two recent open label studies exploring the effect of rTMS over the left parietal cortex found improved behavioral total scores in MCS patients (24) and even in some UWS/VS patients (15). Hence, from these studies, it becomes evident that rTMS is feasible in DoC patients, and that some protocols involving specific target parameters may elicit clinical as well as physiological changes (25), especially in the prefrontal and anterior parietal regions (i.e., DLPFC and angular gyrus, AG).…”