Brain Networks and Consciousness

University of Texas Southwestern Medical Center57 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Loss of Consciousness Parkinson Disease

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Propofol Dose Response Curve

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

Time frame: 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).

Time frame: 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.

Time frame: Baseline