Modulation of cortical functional connectivity and spectrum with transcranial focused ultrasound in chronic disorders of consciousness: A case report

SHU CHENG^1,2Xuan Xu²Lei Lei^3,4Fanyuan Meng²Xiaojing Long⁵Qihui Liang⁶Kaixuan Luo²Xiangjun Feng⁷Moxian Chen^2*Juan Li Ao^2,8*

• ¹Department of Rehabilitation Medicine, China Resources Wuhan Iron and Steel General Hospital, Wuhan University of Science and Technology, Wu Han, China
• ²School of Rehabilitation, Kunming Medical University, Kunming, China
• ³Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation (InnoHK), Chinese Academy of Sciences, Hong Kong Special Administrative Region of China., Hong Kong, China
• ⁴Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
• ⁵Chinese Academy of Sciences Shenzhen Institute of Advanced Technology, Shenzhen, China
• ⁶Yunnan Rehabilitation Center for The Disabled, Kunming, China
• ⁷First Affiliated Hospital of Kunming Medical University, Kunming, China
• ⁸Shanghai Yangzhi Rehabilitation Hospital, Shanghai, China

Objectives: Chronic disorders of consciousness (DOC) represent a profound clinical challenge with few effective therapeutic options. Transcranial focused ultrasound (tFUS) is an emerging non-invasive neuromodulation technique capable of targeting deep brain structures implicated in consciousness, such as the thalamus. In this work, we present a longitudinal, multi-modal investigation into the clinical and neural outcomes following thalamic tFUS in a patient with chronic DOC. Methods: A patient in a chronic minimally conscious state underwent a course of tFUS treatment targeting the right central thalamus. The intervention was applied for 20 minutes, three times per week, over a period of four weeks (12 sessions in total). We conducted comprehensive longitudinal assessments using clinical scales (Coma Recovery Scale-Revised and Glasgow Coma Scale). Besides, resting-state functional near-infrared spectroscopy (fNIRS) to measure cortical functional connectivity, and electroencephalogram (EEG) to analyze neurophysiological dynamics. Results: The patient demonstrated a progressive and clinically significant behavioral recovery, ultimately emerging from the minimally conscious state. This recovery was accompanied by observable neural reorganization. fNIRS revealed a systematic enhancement of functional connectivity, especially within the prefrontal cortex and between prefrontal-sensorimotor networks. Concurrently, EEG analysis showed a marked, progressive suppression of pathological slow-wave (Delta and Theta) power in frontal regions. The intervention was well-tolerated with no adverse events or structural brain changes observed. Conclusions: This case provides cohesive, multi-modal evidence suggesting that targeted thalamic tFUS may be associated with a restorative process, concurrent with the normalization of dysfunctional cortical rhythms and the reintegration of large-scale brain networks that parallel the recovery of consciousness. Our findings offer preliminary insights supporting the continued investigation of tFUS as a potential therapeutic strategy for patients with severe brain injury.