Anesthesia, Essential Tremor, Loss of Consciousness, Parkinson Disease
Conditions
Keywords
general anesthesia, deep brain stimulation, basal ganglia, thalamus, sensorimotor cortex
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.
Interventions
DRUGPropofol
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.
Sponsors
University of Texas Southwestern Medical Center
University of California, Los Angeles
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Propofol Dose Response Curve | Baseline visit | Average targeted serum dose of propofol at which 50% of patients had loss of behavioral responses |
| Behavioral Assessment of Propofol Induced Loss / Recovery of Consciousness and Responsiveness | baseline | 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). |
| Electrocorticogram (ECoG) and Pallidal Local Field Potential (LFP) Recordings | Baseline | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNader Pouratian, MD, PhD
University of Texas Southwestern Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 22 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 12 |
| other Total, other adverse events | 0 / 23 | 0 / 22 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 12 |
| serious Total, serious adverse events | 0 / 23 | 0 / 22 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 12 |
Outcome results
None listed