Saturday, May 17, 2025
5/17/2025
HRV-guided tDCS: Integrating a biomarker for clinical utility - PROJECT SUMMARY / ABSTRACT Transcranial direct current stimulation (tDCS) is a method of noninvasive brain stimulation that is effective for neuropsychiatric symptom targeting when administered in repeated daily sessions. While promising, the mixed results from current RCTs on efficacy may be attributed to inadequate session numbers and marked individual differences in treatment response. We propose to integrate biomarker guidance into tDCS technology to individualize and optimize dosing for improving its clinical utility: (1) tDCS is a well-tolerated and exhaustively characterized neuromodulation technique, effective in targeting neuropsychiatric symptoms, including depression (Level of Evidence: definitely effective); (2) tDCS offers the advantage of home-based administration, remotely controlled through a digital telehealth platform. However, without biomarker guidance, pivotal efficacy trials may be premature. Our Approach is focused on translating these findings into a device. In Aim 1, we will verify the scientific feasibility of tDCS device integration with the nonspecific biomarker of heart rate variability (HRV). By measuring a biomarker that corresponds with the treatment target, its change in response to initial tDCS can indicate if and when an individual will respond. HRV is an emergent and easily obtained biomarker of both tDCS target engagement and neuropsychiatric distress and responsiveness to tDCS. CCNY discovered tDCS impedance-based HR-sensing, which could be integrated seamlessly into this telehealth tDCS system. We will recruit n=100 adults with mild to moderate depression randomized 2:1 to receive 10 sessions of active or sham tDCS. We will verify impedance-based HR data capture (i-HR) in comparison to the standard chest strap ECG, and measure HRV in response to tDCS and in correspondence with the expected change in depression symptoms across the 10 sessions. (1A) tDCS i-HR tracks standard HR, (1B1) is a biomarker of tDCS target engagement, and (1B2) tracks change in depression (MADRS) during the intervention. In Aim 2, data collected in Aim 1 will be used for the technical development of the integrated tDCS-HR device. Aim 2 develops (1) robust signal processing (leveraging machine learning and FEM current-flow models) for i-HR and (2) an integrated FDA-QS-compliant tDCS plus a sensing system. Our team represents key areas of expertise: at-home tDCS, neuropsychiatric, biomedical engineering, and signal processing. With the strength of our remotely supervised tDCS method, this work will result in a biomarker- integrated tDCS telehealth platform, representing an innovative solution customizable to a wide range of hypothesis-driven (targeted engaged) therapy discoveries. At-home treatments reduce disparity in healthcare access, accelerate trial recruitment, and support scalability. Responsive to the NIH priority for the validation of biomarkers “fit for purpose”, this collaboration “between the life and physical sciences” applies a “multidisciplinary bioengineering approach” to “integrate, optimized, validate” and “accelerate the adoption” of “promising solutions to clinical problems”.
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