This proposal provides 5 years of support to train Dr. Forgacs to become an independent clinical investigator, with a research focus on characterizing specific circuit-level neurobiological mechanisms important to recovery of consciousness in patients with severe anoxic brain injury after cardiac arrest.
Neurophysiological studies of recovery of consciousness after cardiac arrest
Deep cerebellar electrical stimulation for post-stroke motor recovery
This project a pilot feasibility study of deep cerebellar brain stimulation in patients who have sustained enduring motor deficits after stroke. Physiological investigations of global and focal neurological disturbances of conscious awareness.
Dynamic multi-lead deep brain stimulation of the central thalamus to treat chronic cognitive deficits in severe-tomoderate traumatic brain injured patients
The goal of this experimental research project is to expand the scope of our existing IP to include specific, measured evidence of critical parameters, i.e. ‘biomarkers’, for ‘closed-loop’ control of fsCT-DBS protocols. Daedalus funding will provide WCM with the sole rights to these new inventions and strengthen our existing IP portfolio potentially broadening the future applications of our new fsCT-DBS system to emerging indications in the rapidly expanding neuromodulation market.
Multi-modal imaging of the mechanisms underlying impaired executive attention after traumatic brain injury
This is a multi-center collaborative grant (Weill Cornell, Mount Sinai) that aims to carry out a longitudinal study of the mechanisms underlying executive attention impairment after TBI. The study will employ EEG and DTI along with neuropsychological assessments in the subacute and chronic stages of recovery to establish biomarkers of impairment and create models of prognosis. The long-term goal of these studies is to enable stratification, improve diagnosis, inform therapeutic interventions and predict prognosis.
Central thalamic stimulation for traumatic brain injury
This is a multi-center, multi-PI collaborative grant (Weill Cornell, Stanford University, Harvard/Spaulding, Cleveland Clinic, University of Utah) that aims to carry out a first-in-man feasibility study of central thalamic deep brain stimulation for the treatment of chronic cognitive impairment after severe-to-moderate brain injuries. The long-term goal of these studies is to establish a new therapeutic avenue for severely brain-injured patients and to develop a new device platform based on pre-clinical studies carried out under 1R01 NS067249.
Central thalamic deep brain stimulation models
This project links three groups of investigators at Weill Cornell (Schiff, ND, Purpura, KP), Rockefeller University (Pfaff, D) and Medical College of Wisconsin (Buston, C) under a multiple PI mechanism (Schiff, ND as Administrative PI) to develop an integrative research program modeling central thalamic brain stimulation as a therapeutic technique. Weill Cornell studies will include the effects of electrical stimulation of the central thalamus on frontal lobe activity during performance of cognitive tasks in the awake primate study. Rockefeller University work focuses on rodent studies of central thalamic brain stimulation in animal models of brain injury and the University of Wisconsin provides bioengineering support in modeling of applied electric field in the primate and rat thalamus.
Mechanisms of recovery following severe brain injury
This project develops a multi-modal brain imaging assessment of minimally conscious state patients following severe brain injuries using FDG-PET, quantitative EEG and DTI and functional MRI. Several mechanistic hypotheses are tested related to the role of the corticothalamic system in recovery of consciousness following severe brain injuries.
Collaborative study of recovery of consciousness after severe brain injury: Phase II
This multi-center collaborative grant (Cambridge U, UK; U. Liege, Belgium; Hebrew University, Israel; Western U, Canada; U Paris, France; Weill Cornell, Columbia, Mount Sinai, Harvard/Spaulding, USA) aims to test a core battery of evaluations using fMRI and EEG technologies across patients with a broad ranges of functional outcomes and etiologies of brain damage to assess recovery of function. The goal of the studies is to establish validated diagnostic tools for use in assessment of severely brain-injured patients. https://www.jsmf.org/grants/2013018/
Physiological investigations of global and focal neurological disturbances of conscious awareness
This protocol supports scatter-bed admissions of neurological patients with moderate to catastrophic brain injury for combined clinical evaluation and functional brain imaging with fluoro-deoxyglucose-positron emission tomography (FDG-PET, magnetic resonance imaging (MRI), and electroencephalography (EEG).
Dopaminergic system in disorders of consciousness
This protocol is aimed at understanding the role the dopaminergic system plays in mechanisms of recovery of impaired consciousness, using [11C]raclopride-PET. The goal of this study is to determine if disorders of consciousness have an underlying dopaminergic deficit and if recovery from severe disorders of consciousness progressively involves a plastic reorganization of the dopaminergic system.
Neuroethics and Disorders of Consciousness I and II
This grant provides funding to assess the scope of misdiagnosis and neglect of patients with disorders of consciousness, consider why these patients are marginalized and outside the public eye, and develop educational materials to instruct physicians on diagnostic and prognostic skills.
Neuroethics And Disorders Of Consciousness: A Qualitative And Quantitative Assessment Of Clinical Practice And Healthcare System Epidemiology/Barriers To Care
This protocol aims to get a better understanding of the patient/family experience in cases involving disorders of consciousness. The goal of this study is to improve communication between physicians and families, gain clinical insight to develop better diagnostic and prognostic tools for assessing these patients, and to inform policy in this area.
Imaging of cortical network function in three models of small-scale stroke
In this functional neuroimaging study we will investigate the effects of small-scale stroke on neuronal network function in a rodent model. Small-scale stroke is believed to be a determining factor for neurological diseases such as dementia and Alzheimer’s disease.
The aim of this protocol is to determine the relative efficacy of two computer-based programs designed to enhance attention in a set of normal 18-25 year olds. Functional improvement will be assessed by neurocognitive performance on set of standardized tests, data that will be correlated with a set of MR-based brain imaging biomarkers reflective of structural brain connectivity.
Decisional Analysis of Informed Consent in Surrogate Decision Makers
This project is aimed at learning how surrogates of patients with disorders of consciousness understand the consent process when enrolling the patient in research and decide whether or not to participate. We are interested in understanding their decisional process and risk for holding a therapeutic misconception. The project utilizes the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) to assess the surrogate’s decision making process to consent the patient to research. This oral, structured interview will gauge the degree to which they understand and appreciate the significance of information disclosed during a consenting process for a hypothetical clinical research study.
Minds Apart: Severe Brain Injury and Health Policy
This Robert Wood Johnson Foundation Investigator Award in Health Policy Research will fund interdisciplinary research into how best to serve the needs of patients with severe brain injury and their families through better clinical services and the promotion of clinical research. The work is designed to improve clinician-family communication about brain injury, inform educational standards for professionals, and articulate a justification for research in patients who are unable to provide consent.
Sustaining and Building Research Infrastructure for the Study of Disorders of Consciousness at Weill Cornell Medical College and Rockefeller University
This protocol aims to create a dedicated unit at Rockefeller University Hospital that will provide an ideal setting in which to initiate new research in clinical science and translational neuroethics, focusing on the prognosis and treatment of seriously brain-injured patients.
Surrogates and the Injured Self: How Surrogates Make Decisions for Patients with Disorders of Consciousness: A Pilot Study
This project aims to understand what biases surrogate decision makers for patients with disorders of consciousness have and how these impact their choices for those patients. The primary goal of this study is to gain a better understanding of the experiences that surrogates of patients with DOC have and how these experiences shape their motivations to pursue therapeutic interventions or secure diagnostic clarity for the patient.