A naturalistic multimodal platform for capturing brain-body interactions in people during physical effort-based decision making - PROJECT SUMMARY The challenge of understanding how neural activity results in human behavior and cognition in health and disease is a crucial one for neuroscience. Traditional research methods often employ abstract tasks focusing on discrete cognitive processes, which may not fully capture the complexity of real-world behaviors and their neural underpinnings. This limitation has hindered progress in understanding and treating psychiatric disorders. In particular, motivational deficits, characterized by a reduced propensity to expend effort for rewarding outcomes, are pervasive across various disorders like major depression as well as many others (e.g., Parkinson's disease, schizophrenia). This deficit in effort-based decision- making (EBDM) leads to reduced quality of life in patients who experience these symptoms. To address this gap, there is a need to employ naturalistic paradigms with concurrent measurements of different systems of the body to characterize behavior comprehensively. The proposed project aims to develop and pilot a platform for synchronized multimodal measurement, the HOlistic Realtime Measurement of Effort-based deciSion-making (HORMES) system. The HORMES system will be centered around a new naturalistic EBDM (nEBDM) task in an immersive virtual environment requiring effortful locomotion. The system will measure behavior across decision-making, embodied, affective, and clinical domains, synchronized with measurements of relevant neural circuits at appropriate spatial and temporal scales, and include new analysis methods based on latent variable models to characterize brain-body interactions. The project consists of two phases: the R61 phase activities will include the design and refinement of the HORMES system using data from healthy participants and patients with major depression, while the R33 phase will pilot the system in a clinical trial with treatment-resistant depression patients undergoing subcallosal cingulate cortex deep brain stimulation. This experimental neuromodulation therapy often leads to changes in psychomotor, interoceptive, and cognitive symptoms at different timescales, as well as provides access to intracortical electrophysiology with extreme spatial specificity in a brain network known to be critical in nEBDM. Taken together, this trial is an ideal context for a pilot evaluation of the HORMES system in a longitudinal study. Furthermore, the project integrates neuroethics research and involves the creation of a Council of Lived Experience Advocates (CLEA), comprising patients with intracranial implants across a variety of disorders. The CLEA will provide input on the HORMES project and offer guidance on the ethical implications and future applications of high-resolution biobehavioral data. Successful completion of the project is expected to advance our understanding of motivational deficits and inform novel treatment for symptoms, representing a significant step towards bridging the gap between basic neuroscience research and clinical practice in psychiatry.
