Rapid Entrainment and Signal-guided Neuromodulation for Behavioral Health

RESYNC-BH is a prospective, adaptive, transdiagnostic behavioral health study evaluating a personalized intervention platform (PRESET-Rx) and multimodal measures of treatment response. The study examines rapid within-session changes and longitudinal changes in neurophysiologic, autonomic, cognitive, inflammatory, and behavioral measures.

Participants receive a personalized combination of noninvasive neuromodulation and AIP-informed integrative psychotherapy based on baseline symptoms, physiologic measures, and clinical presentation. Study interventions may include noninvasive brain or peripheral nerve stimulation, regulated breathing, sensory stimulation using light, sound or vibration, and related noninvasive techniques. Treatment assignment and adaptation occur according to prespecified study criteria.

Multimodal assessments include EEG/qEEG, fNIRS, heart rate and heart rate variability, cognitive testing, standardized behavioral health measures, and inflammatory biomarkers. Selected sessions include simultaneous clinician-participant physiologic recording to evaluate therapeutic dyad dynamics. Optional data from compatible personal wearable devices may also be collected to characterize sleep, activity, and related physiologic patterns outside the clinic.

The acute treatment phase consists of approximately six structured sessions over 4-6 weeks, followed by longitudinal assessments of treatment response and durability.

Some participants may independently receive ketamine as part of routine clinical care. Ketamine is not a study intervention and is not assigned, initiated, scheduled, administered, or modified by the study. Ketamine exposure is recorded as a concomitant clinical treatment and may be considered in study analyses.

Inclusion criteria

• Age 18 to 70 years at the time of consent
• Able to understand the study and provide signed informed consent
• Willing and able to comply with study procedures and follow-up assessments for approximately 12 months
• Presence of clinically significant behavioral-health symptoms and/or functional impairment in at least one of the following domains, as determined by clinical interview and standardized measures:
• Depressive symptoms
• Anxiety symptoms
• Trauma- and stressor-related symptoms
• Substance-related symptoms not requiring immediate detoxification
• Attentional/impulsivity or executive-function symptoms
• A formal DSM-5 diagnosis is not required if symptoms and impairment are clinically meaningful and appropriate for outpatient behavioral-health intervention
• Medically stable, in the judgment of the investigator, for outpatient behavioral-health treatment and applicable noninvasive neuromodulation or multisensory entrainment
• If taking psychotropic or other relevant medications, on a stable dose for at least 4 weeks before baseline, with no planned changes during the acute intervention phase except as clinically necessary
• Sufficient proficiency in English or another IRB-approved language to understand study procedures and provide informed consent, with approved translated materials or interpreter support when available
• If of reproductive potential, agrees to applicable pregnancy-prevention requirements during the acute intervention phase
• Willing to follow study lifestyle and safety requirements, including restrictions on alcohol and substance use before study sessions and applicable post-session safety recommendations

Exclusion criteria

• History of seizure disorder or other condition that, in the investigator's judgment, would make exposure to stroboscopic or patterned light stimulation unsafe
• Severe photosensitivity or light sensitivity that could be worsened by exposure to flashing or patterned light
• Implanted electronic or other medical device that is incompatible with study neuromodulation procedures
• Unstable or clinically significant cardiovascular, neurologic, or other medical condition that could make study participation unsafe
• Unstable or high-risk psychiatric condition, including:

• Recent suicide attempt or current imminent suicide risk
• Active psychosis
• Uncontrolled mania or other acute psychiatric instability requiring a higher level of care
• Pregnant or breastfeeding at screening or during participation
• Acute intoxication or inability/unwillingness to comply with study safety restrictions regarding alcohol or non-prescribed/recreational substance use before study sessions
• Unstable or rapidly changing psychotropic medication regimen at baseline
• Concurrent participation in another interventional trial targeting behavioral health or neuromodulation that, in the investigator's judgment, would confound study outcomes or create a safety concern
• Any other medical, psychiatric, cognitive, or behavioral condition that, in the investigator's judgment, would prevent safe participation or meaningful completion of study procedures