Risk of low-frequency ultrasound stimulation: Response to Brain injury during focused ultrasound neuromodulation for substance use disorder

Low-intensity transcranial focused ultrasound (tFUS) stimulation is an emerging non-invasive neuromodulation technique with potential applications in the treatment of neurological and psychiatric disorders, including substance use disorders. However, recent reports of serious adverse events have raised important questions regarding the safety of low-frequency ultrasound protocols and the influence of acoustic exposure parameters on brain tissue. This letter addresses concerns arising from a previously reported case of brain injury during focused ultrasound neuromodulation for substance use disorder and emphasizes the importance of detailed characterization of sonication parameters when evaluating the safety of tFUS. Particular attention is given to acoustic intensity, mechanical index, ultrasound frequency, and other exposure characteristics that may influence the likelihood of unintended bioeffects, including inertial cavitation. The authors acknowledge the limitations associated with incomplete reporting of acoustic parameters in earlier studies and highlight the need for standardized and transparent reporting to facilitate meaningful comparisons across experimental protocols. Importantly, the reported adverse event should be interpreted within the context of the specific ultrasound system, stimulation parameters, and treatment conditions rather than being generalized to all forms of low-intensity ultrasound neuromodulation. The available evidence supports continued investigation of tFUS while emphasizing rigorous safety assessment, precise acoustic characterization, appropriate exposure limits, and systematic monitoring of adverse effects. Further experimental and clinical research is required to establish parameter-specific safety margins and to support the responsible translation of low-frequency focused ultrasound neuromodulation into clinical practice.