Characterizing central thalamic regulation of altered states of awareness in humans

The National Institute of Neurological Disorders and Stroke awarded Brown University $110,228 on December 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to characterize central thalamic regulation of altered states of awareness in humans.

The research probes frequency-specific changes in thalamocortical and corticocortical synchronization during behavioral tasks designed to assess selective attention and auditory response in relation to different dimensions of consciousness. The investigator will test how thalamic stimulation modulates circuit dynamics and resulting behavior, using two behavioral paradigms—an attentionally demanding selective-focus task and a simple auditory response task—in patients undergoing intracranial clinical monitoring in the epilepsy monitoring unit and operating room. The work aims to advance understanding of thalamic involvement in disorders of consciousness resulting from generalized seizures, traumatic brain injury, and related conditions, and to support development of neuromodulatory treatments for these patients.

Performance of research will occur in Providence, Rhode Island. The period of performance runs through August 31, 2030. The assistance type is Project Grant.

Abstract

Consciousness is a complex, often ambiguously define phenomenon that is thought to rely on coordinated activity between cortical and subcortical regions. DOC represent a heterogenous group of conditions, from loss of awareness during generalized seizures to coma resulting from traumatic brain injury. Prolonged DOC can significantly impact the lives of patients and their families and contribute to healthcare costs at an individual and systemic level. DOC patients also often present with disorders of attention, including problems sustaining attention and difficulty focusing on specific tasks. Providing care for these patients with prolonged DOC is challenging due to an incomplete understanding of the cortical and subcortical circuits involved in regulating awareness and attention, although thalamocortical (TC) circuit dynamics are thought to play an important role. Here, we use two behavioral paradigms-one attentionally demanding task that assesses the ability to selectively focus attention and one simple auditory response task-to probe frequency-specific changes in central TC and corticocortical (CC) synchronization that relate to different dimensions of consciousness, from overt awareness to more subtle attentional control. We will also test how thalamic stimulation can modulate the circuit dynamics and resulting behavior in these tasks. Patients undergoing intracranial clinical monitoring will perform these tasks in the epilepsy monitoring unit and operating room. We hypothesize that the central thalamus governs both awareness and attention via frequency-dependent modulation of TC and CC connectivity, enabling flexible, state-dependent regulation of information processing. Overall, this work may improve our understanding of thalamic involvement in DOC, and aid in the development of neuromodulatory treatments for these patients. I am currently an MD/PHD student in the third year of my dual-degree training at brown university. My long-term goal is to become an academic physician-scientist focused on understanding the circuit mechanisms that underlie loss and recovery of awareness. Through a 50/50 balance of research to clinical practice, i hope to translate findings from my laboratory to improve the care of patients with DOC. The proposed projects will allow me to accomplish these goals by developing expertise in acquiring and analyzing human neurophysiologic data, using computational modeling methods to understand circuit dynamics, and performing mechanistic testing of stimulation to move the field towards therapeutic neuromodulation for DOC. Furthermore, these projects will integrate neurophysiology training with my previous behavioral neuroscience experience. The sponsor team will share their expertise in human neurophysiology, in-human stimulation experiments, and clinical management of disorders of consciousness. Further training will be obtained from workshops and courses offered through the department of neuroscience, grand rounds in the department of neurosurgery and neurocritical care, and presenting at conferences. Overall, this proposal will provide both rigorous technical training and career development opportunities necessary for my professional growth.