Active Projects

Electrophysiological Biomarkers to Optimize Deep Brain Stimulation for Depression 

PI: Helen Mayberg. NIH BRAIN 1UH3NS103550
The Icahn School of Medicine at Mount Sinai is running a single-center experimental trial of deep brain stimulation (DBS) to the subcallosal cingulate region (Area 25) for treatment-resistant depression. The goal of this study is to refine and optimize this treatment approach using a newly available neuromodulation system (the Medtronic Summit RC+S) that allows brain activity during ongoing therapeutic DBS to be recorded from the brain in real time. This study will further define brain readouts that track depression recovery, providing novel strategies to monitor and guide treatment and device-programming decisions in patients receiving DBS for treatment-resistant depression.
To enroll in the study, please contact Emma Meyer at 212-241-6539 or dac@mssm.edu.
For more information, visit Mount Sinai Clinical Trials or https://clinicaltrials.gov/ct2/show/NCT04106466

Divergent Attitudes About Brain Implants for Movement, Mentation, or Mood: Rational Concern or Thinking Error?

PI: Allison Waters. NIH BRAIN UH3 NS103550-S1
Misunderstanding of moral concerns about the application of DBS to psychiatric problems is a critical barrier to effective dissemination, construction of relevant policy, and development of rehabilitative services that surround the DBS experience. Our research seeks to understand the mechanisms (e.g., dualistic thinking errors) that give rise to discrepancies in comfort with DBS for motor, mood, or cognitive symptoms, as well as demographic moderators of concern among the public. Particularly as we build regulations around closed-loop systems, policies guiding DBS for movement disorders may not be sufficient to address public concerns about neurotechnology-mediated changes in mood and cognition.
For more information, visit Waters Lab

Individualized Brain Mapping with Deep Brain Stimulation Evoked Potentials

PI: Allison Waters
Some treatments with DBS target specific neuronal pathways (i.e., white matter fibers). Electric fields generated by the cortical response to brain stimulation can be used as a measure of “effective connectivity” in the brain. We are investigating how these stimulation-induced connectivity measures can be used to confirm DBS target engagement in white matter architecture and to instruct optimal DBS programming for individual patients.
For more information, visit Waters Lab

Human Electrophysiological Mechanisms of the Rapid Antidepressant Response to Ketamine

PIs: Allison Waters, James Murrough. FBI Research Scholars Program
Treatment-resistant depression (TRD) represents a severe and disabling condition characterized by significant functional impairment, non-response to conventional antidepressants, and a high risk for suicide. Complementary mechanisms of action are attributed to successful treatment of TRD with deep brain stimulation (DBS) or ketamine. The proposed research will test if an EEG-derived biomarker of the antidepressant response to DBS also predicts outcomes following ketamine infusion. Results will provide critical rationale for a novel treatment approach that enhances DBS efficacy with a combined ketamine-DBS approach.
For more information, visit Waters Lab

Assessment at the Transdiagnostic Quantitative Biometrics Laboratory (Q-LAB)

PI: Helen Mayberg. Hope for Depression Research Foundation
Clinical response to DBS treatment is currently measured using qualitative assessments, combining clinical exams and standardized rating scales. While generally effective, this existing strategy is inadequate to detect or track subtle DBS changes. We hypothesize that effective predictors of therapeutic benefit, functional recovery, and/or disease progression may be derived across diagnoses from a combination of neural measures and objective assessment of naturalistic behaviors. To test this hypothesis, we have established the Quantitative Biometrics Laboratory (Q-Lab) in C-ACT at Mount Sinai West: an expandable, modular experimental platform that collects and archives a comprehensive battery of mood, motor, cognitive, and neural assessments. To test our hypotheses, we will recruit individuals from three groups in this protocol: 1) patients who have undergone or will undergo DBS for their symptoms across diagnostic groups, 2) patients receiving treatment for the same diagnoses but who will not receive DBS, 3) healthy control subjects (no history of/current psychiatric or medical diagnoses). Within this environment, participants will perform a standard battery of directed and naturalistic behavior assessment (movement, speech) with associated audiovisual recording, as well as complete interviews and/or self-report questionnaires using validated clinical assessment instruments.
For info: maybergqlab@mssm.edu

A Multiscale Investigation of the Living Human Brain

PI: Alexander Charney, NIMH 1R01MH123765
The Living Brain Project (LBP) is a novel framework for human brain research pioneered by our team wherein a vast data landscape is surveyed in individuals undergoing deep brain stimulation (DBS). Prior to the LBP, it was not considered feasible to safely obtain brain specimens at the requisite scale and in the proper controlled settings for rigorous scientific inquiry into the neurobiological basis of neuropsychiatric traits in living people. Since 2013, we have performed more than 300 DBS surgeries where paired samples of the prefrontal cortex (PFC) and blood were obtained. Applying state-of-the-art high-throughput multiomic profiling to these specimens has created what we believe to be amongst the most comprehensive molecular maps of the living human brain. Integrating this high-dimensional dataset with the diverse data landscape generated on the same patients by other branches of C-ACT allows us to obtain a more holistic understanding of brain function in each individual. 

Computational and Electrochemical Substrates of Social Decision Making in Humans

PI: Xiaosi Gu.  NIMH R01MH124115
Dopamine and serotonin jointly influence a broad range of healthy cognition, and changes in their delivery or action are thought to underpin a variety of pathological conditions including major depressive disorder, drug addiction, attention-deficit-hyperactivity disorder, and Parkinson’s disease. During the window of opportunity afforded by deep brain stimulating electrode implantation, we will make the first recordings of joint dopamine and serotonin dynamics in the striatum of conscious humans during the execution of inter-personal social exchange games. This work will address for the first time how these important neuromodulators encode social processes important for healthy cognition and affected by disease and injury.

Connectomic Deep Brain Stimulation for Obsessive-Compulsive Disorder

PI: Ki Sueng Choi and Martijn Figee.  NIMH 1R01MH123542
Deep brain stimulation is an emerging treatment for individuals suffering from severe obsessive-compulsive disorder (OCD), which is a common and disabling neuropsychiatric condition. To prepare this treatment for broad dissemination, we must build the knowledge and tools to enhance the precision with which stimulation is applied to individual brains. This research constructs a connectomic atlas for deep brain stimulation in OCD using the association of brain pathways and optimal behavioral outcomes. 
For more information:
https://www.mountsinai.org/locations/center-neuromodulation/conditions
https://www.mountsinai.org/care/behavioral-health/services/ocd-tics/dbs