Brain Networks and Consciousness

Parkinson Disease Clinical Trial

Official title:

Subcortical-cortical Network Dynamics of Anesthesia and Consciousness

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04502550
• Other study ID #: STU-2021-0396
• Status: Recruiting
• Start date: October 15, 2020
• Est. completion date: August 15, 2025

Study information

• Verified date: January 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Nader Pouratian, MD, PhD
• Phone: (214)645-5465
• Email: nader.pouratian[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

General anesthesia (GA) is a medically induced state of unresponsiveness and unconsciousness, which millions of people experience every year. Despite its ubiquity, a clear and consistent picture of the brain circuits mediating consciousness and responsiveness has not emerged. Studies to date are limited by lack of direct recordings in human brain during medically induced anesthesia. Our overall hypothesis is that the current model of consciousness, originally proposed to model disorders and recovery of consciousness after brain injury, can be generalized to understand mechanisms of consciousness more broadly. This will be studied through three specific aims. The first is to evaluate the difference in anesthesia sensitivity in patients with and without underlying basal ganglia pathology. Second is to correlate changes in brain circuitry with induction and emergence from anesthesia. The third aim is to evaluate the effects of targeted deep brain stimulation on anesthesia induced loss and recovery of consciousness. This study focuses on experimentally studying these related brain circuits by taking advantage of pathological differences in movement disorder patient populations undergoing deep brain stimulation (DBS) surgery. DBS is a neurosurgical procedure that is used as treatment for movement disorders, such as Parkinson's disease and essential tremor, and provides a mechanism to acquire brain activity recordings in subcortical structures. This study will provide important insight by using human data to shed light on the generalizability of the current model of consciousness. The subject's surgery for DBS will be prolonged by up to 40 minutes in order to record the participant's brain activity and their responses to verbal and auditory stimuli.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: August 15, 2025
• Est. primary completion date: February 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willingness and ability to cooperate during conscious operative procedure for up to 40 minutes

• Clinical diagnosis of Parkinson's disease or essential tremor

• Preoperative MRI without evidence of cortical or subdural adhesions or vascular abnormalities

Exclusion Criteria:

• Patients with recent use (within one week) of anticoagulant or antiplatelet agent use

• Neurocognitive testing indicating amnestic cognitive deficits

• History of intolerance of propofol or medical indications to use an anesthetic other than propofol

Related Conditions & MeSH terms

• Anesthesia
• Essential Tremor
• Loss of Consciousness
• Parkinson Disease
• Unconsciousness

Intervention

Drug:
• Propofol
Target effect-site concentration of propofol will be started at 1.4 µg/mL and will be increased by 0.3 µg/mL with reassessment until endpoints are achieved.

Locations

Country	Name	City	State
United States	Nader Pouratian	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Propofol dose response curve	Serum concentration of propofol throughout targeted infusion will be correlated with the patient's response to behavioral assessments in order to predict the time course of plasma and effect site concentration of propofol, establishing differential anesthetic sensitivity profiles.	baseline
Primary	Behavioral assessment of propofol induced loss / recovery of consciousness and responsiveness	For each experiment, three behavioral responses will be evaluated: (1) loss/recovery of spontaneous movement (i.e., loss and recovery of responsiveness) (2) loss/recovery of movement in response to stimuli (separately to clicks [non-salient] and verbal stimuli [salient]), and (3) loss/recovery of movement to command (verbal command with patient name with instruction to open their eyes, as proxy of loss/recovery of consciousness).	baseline
Primary	Electrocorticogram (ECoG) and pallidal Local Field Potential (LFP) recordings	Cortical ECoG and Globus Pallidus internus / Globus Pallidus externus (GPi/GPe) LFP recordings will occur during DBS implantation surgery during both induction and emergence with target-controlled infusion of propofol changes in network parameters. Neurophysiological signals will be correlated the evolution of behavioral measures of loss of consciousness and responsiveness during propofol infusion.	baseline