An Exploratory Study on the Effectiveness and Safety of Temporal Interference Stimulation in Treating Patients With Severe Consciousness Disorders

Based on the central loop hypothesis, deep brain stimulation (DBS) represents a commonly utilized neuro-modulation stimulation technology for disorders of consciousness (DOC). It was initially employed in Europe in 1968 for treating DOC. Some patients can regain functional communication capabilities and even resume family life. Nevertheless, as a neurosurgical intervention, DBS implantation entails significant surgical risks and potential complications (such as cerebral edema in the surgical area, secondary cerebral hemorrhage, secondary epilepsy, postoperative brain abscess, pulse generator shutdown or circuit malfunction, displacement of stimulation electrodes or extension leads, rejection reactions), and incurs substantial costs, imposing a heavy burden on patients' families and the national medical insurance fund. Traditional non-invasive brain stimulation methods, such as transcranial alternating or direct current stimulation, although not requiring surgery, have limited focusing capacity and the ability to stimulate deep brain structures. Hence, researchers have been in pursuit of approaches to precisely and effectively stimulate deep brain regions without the need for surgery.

In 2017, the concept of temporal interference (TI) stimulation, a novel non-invasive method for regulating deep brain regions was put forward . The fundamental principle of TI stimulation is that two interfering high-frequency signals will generate a low-frequency amplitude-modulated electric field, which can drive the discharge of deep brain neurons. Furthermore, by fixing the sum of the input currents of two pairs of electrodes and altering the current input ratio of the two pairs of electrodes, the movement of the mouse's forepaws, whiskers, and ears without modifying the spatial position of the electrodes could be achieved. Therefore, TI stimulation enables the flexible movement of the stimulation target area within the brain without electrode displacement. Despite the fact that research on TI technology is still in its nascent stage, this method has demonstrated substantial potential in neuroscience and clinical therapy.

Given the early stage of TI stimulation and the limited clinical evidence in patients with DOC, and because, to date, no TI device has received marketing approval from the U.S. Food and Drug Administration (FDA) or the National Medical Products Administration (NMPA), this is a small-sample exploratory randomized controlled trial (RCT) conducted under the regulatory oversight of the NMPA, in accordance with its investigational medical device filing and/or approval requirements, and approved by the ethics committee. This study aims to preliminarily assess the safety, tolerability, and feasibility of TI stimulation in patients with severe DOC and to explore operational parameters including electrode montage, current intensity, frequency configuration, and stimulation duration. The secondary exploratory objective is to obtain preliminary behavioral therapeutic signals. In addition, this study collects EEG, functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and functional near-infrared spectroscopy (fNIRS) data before and after treatment, and integrates these four modalities to explore the potential neural mechanisms underlying recovery associated with TI stimulation in DOC, thereby providing hypothesis-generating evidence for future large-sample confirmatory RCTs.