Portable TMS-EEG device for bedside detection of covert consciousness

Project Summary Disorders of consciousness (DoC) due to severe brain injury affect more than one million people worldwide each year. Withdrawal of life-sustaining therapy (WLST) is the cause of ~80% of deaths in patients with DoC in intensive care unit (ICU) settings; yet WLST decisions are often made by families and caregivers without a clear understanding of their loved one’s state of consciousness or potential for recovery. Over the last twenty years, the physician-scientists who founded Intrinsic Powers, Inc. and the PI developed and validated a method combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) that has unprecedented sensitivity and specificity (>95%) to diagnose covert consciousness. However, this method requires lengthy data acquisition and processing with 60 EEG channels, which makes it impractical in ICU settings. In the present STTR, Intrinsic Powers and the PI and her team propose to fill this gap by developing Presence, a new portable TMS-EEG device combining a new complexity algorithm, Presence-IP1.0, computed in real-time with 21 electrodes and without the need for an MRI, combined with a portable data acquisition system integrated into a wheelable cart, that will maximize the clinical utility for the ICU. In this Phase 1 STTR, we propose to: 1) refine the product vision and value propositions for the use of Presence in the ICU; and 2) validate the accuracy of the new Presence-IP1.0 algorithm on a prospective dataset. Our product vision and value proposition (Aim 1) will be refined through systematic semi-structured interviews of end-users and stakeholders to define how Presence will help to guide clinical decision-making and to ascertain the optimal trade-off between accuracy and user-friendliness to maximize clinical utility (Aim 1). Our milestone for Aim 1 will be the collection of 100 semi-structured interviews. In parallel, we will validate the accuracy of Presence- IP1.0 to detect consciousness in a prospective sample of 30 subjects (half from ethnic minorities) acquired with TMS combined with 21 EEG channels during wakefulness and sleep (Aim 2). Our milestone for Aim 2 will be to show that Presence-IP1.0 can achieve clinically useful accuracy (as determined by user feedback from Aim 1) to differentiate conscious from unconscious states in the prospective dataset. Finally, for Aim 3, we will hold a PreSubmission meeting with the FDA. The work performed in this Phase I STTR will open the way to Phase II multi-centric ICU studies to validate the diagnostic and prognostic utility of Presence in the ICU. We expect Presence to become widely used, triggering a transformative shift in the care of DoC patients in the ICU by enabling physicians to detect consciousness and predict patients’ recovery even in difficult cases quickly and precisely. Such innovative technology will significantly decrease burn-out of families and caregivers and reduce costs of care thanks to a decreased length of ICU stays and a more efficient distribution of limited life-saving ICU resources.