Brain Networks and Consciousness

NCT04502550 | Terminated Results DMC

• 1 other identifier: STU-2021-0396
• Study Type: observational
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Essential Tremor; Anesthesia; Loss of Consciousness; Parkinson Disease

Keywords

general anesthesia; deep brain stimulation; basal ganglia; thalamus; sensorimotor cortex

Outcome Measures

Primary Outcomes (3)

• Propofol Dose Response Curve

  Average targeted serum dose of propofol at which 50% of patients had loss of behavioral responses

  Baseline visit

• Behavioral Assessment of Propofol Induced Loss / Recovery of Consciousness and Responsiveness

  Number of participants with loss of at least 50% of behavioral responses at a targeted serum concentration of 1.5 ug/mL using the following 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

• Electrocorticogram (ECoG) and Pallidal Local Field Potential (LFP) Recordings

  Oscillatory frequency at which maximal power changes occur with inducing loss of consciousness, as measured using ECoG and Globus Pallidus internus / Globus Pallidus externus (GPi/GPe) LFP recordings during DBS implantation surgery with target-controlled infusion of propofol. This is not an average frequency but a single peak value based on population spectra at which maximal changes are noted. The number reported is not an average of peaks across patients, but the peak identified after integrating data across the population studied. There is no corresponding measure of dispersion or prevision based on the way the value is identified. Rather, it is a single peak value.

  Baseline

Study Arms (7)

Parkinson's Disease patients with DBS, no stimulation

This cohort will serve as as the observed group, displaying basal ganglia pathology. A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. 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. Experiments will be completed with DBS off.

Drug: Propofol

Essential Tremor patients with DBS

This cohort will serve as a control group (no basal ganglia pathology). A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a TCI system to achieve plasma target propofol concentrations. 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. Experiments will be completed with DBS off.

Drug: Propofol

Parkinson's Disease patients with DBS, Gpi stimulation

This cohort will serve as as the observed group, displaying basal ganglia pathology. A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. 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. Participants will be stimulated at the Gpi via DBS leads during propofol induced loss of consciousness.

Drug: Propofol

Parkinson's Disease patients with DBS, Gpe stimulation

This cohort will serve as as the observed group, displaying basal ganglia pathology. A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. 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. Participants will be stimulated at the Gpe via DBS leads during propofol induced loss of consciousness.

Drug: Propofol

Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. 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. Participants will be stimulated at the Gpe via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.

Drug: Propofol

Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. 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. Participants will be stimulated at the Gpi via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.

Drug: Propofol

Parkinson's Disease patients undergoing DBS surgery, no stimulation

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. 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. Participants will not receive any stimulation via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.

Drug: Propofol

Interventions

Propofol DRUG

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.

Essential Tremor patients with DBS; Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation; Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation; Parkinson's Disease patients undergoing DBS surgery, no stimulation; Parkinson's Disease patients with DBS, Gpe stimulation; Parkinson's Disease patients with DBS, Gpi stimulation; Parkinson's Disease patients with DBS, no stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Study participants are Parkinson's disease and essential tremor patients undergoing revision/replacement of an implantable pulse generator for DBS, or initial DBS implantation.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: collaborator
• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Nader Pouratian

Dallas, Texas, 75235, United States

Location

MeSH Terms

Conditions

Unconsciousness; Parkinson Disease; Essential Tremor

Interventions

Propofol

Condition Hierarchy (Ancestors)

Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr Nader Pouratian
• Organization: UT Southwestern Medical Center

nader.pouratian@utsouthwestern.edu

2146489320

Study Officials

• Nader Pouratian, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: August 6, 2020
• Study Start: October 15, 2020
• Primary Completion: November 14, 2024
• Study Completion: December 31, 2025
• Last Updated: June 8, 2026
• Results First Posted: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)