Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit

There are currently no therapies proven to promote early recovery of consciousness in patients with severe brain injuries in the intensive care unit (ICU). Early recovery of consciousness would benefit patients and families by reducing the likelihood of premature withdrawal of life-sustaining therapy and may decrease ICU complications related to immobility, facilitate self-expression, enable autonomous decision-making, and increase access to rehabilitative care. Here, we present the connectome-based clinical trial platform (CCTP), a new mechanistic paradigm for developing and testing targeted therapies that promote early recovery of consciousness in the ICU. The scientific premise of the CCTP is that personalized brain connectome maps can be used to select patients for targeted therapies that promote recovery of consciousness. Structural and functional MRI connectome maps will identify circuits that may be amenable to neuromodulation. Patients will be selected for clinical trials in the CCTP paradigm based on connectomes that are likely to respond to targeted therapies. To demonstrate the utility of this precision approach, we describe STIMPACT ( S timulant T herapy Targeted to Individualized Connectivity M aps to P romote Re ACT ivation of Consciousness), a CCTP-based clinical trial in which intravenous methylphenidate will be used to promote early recovery of consciousness in the ICU (ClinicalTrials.gov NCT03814356 ). We propose that the CCTP has the potential to transform the therapeutic landscape in the ICU and improve outcomes for patients with severe brain injuries.