Clinical trial

Simultaneous EEG-fMRI Study in Healthy Humans During Induction of Propofol Anesthesia to Investigate the Dynamics of Thalamocortical Functional Connectivity in the Alpha Frequency

Name

PropofolStudyTUM2023

Description

This observational study aims to investigate healthy cortical and subcortical neural processes involved in generating intrinsic alpha oscillations during induction of general anesthesia with propofol. To do this, the investigators have designed a simultaneous electroencephalogram (EEG)- MRI (functional MRI and Spectroscopy) experiment with a visual stimulation paradigm that addresses the subject's specific intrinsic alpha rhythm during anesthesia and wakefulness. The main question it aims to answer is: could the investigators address the alpha oscillation system of the healthy brain with external stimulation during anesthesia? This experiment could lead to a better understanding of the mechanisms underlying the generation of alpha oscillations. It could open new doors to diagnostic and treatment options for diseases where alpha oscillations, such as post-operative delirium, seem to be affected.

Trial arms

Trial start

2023-09-10

Estimated PCD

2024-09-10

Trial end

2026-09-10

Status

Recruiting

Treatment

Propofol

Anesthesia will be induced intravenously using the hypnotic drug propofol. The drug is used regularly in everyday clinical practice to carry out general anesthesia, and the intended concentrations are within the usual clinical dosage range. Propofol will be applied via target-controlled infusion (TCI) with a perfusor using TCI set to effect mode as described by Schnider (Schnider et al., 2016). Starting at low concentrations, the effect site concentration will be increased stepwise to achieve the target level of sedation as measured by the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale. We aim for three different levels of sedation: low (MOAA/S=5-4), mid (MOAA/S=3-2) and high (MOAA/S=1).

Arms:

Healthy controls

visual flickering stimulation at the alpha frequency

Participants will receive visual stimulation as a flickering light during the different sedation levels, including wakefulness pre- and post-anesthesia. Stimulation will be done with eyes closed in all conditions.

Arms:

Healthy controls

Size

Primary endpoint

Visual stimulation at the intrinsic alpha frequency will be related to a change in synchronization in the EEG compared to flankers across all conditions (i.e., wakefulness pre-anesthesia and propofol sedation at low, mid, and high concentrations.

12 months

Visual stimulation at the intrinsic alpha frequency will elicit a change in functional connectivity between the thalamus and the cortex during wakefulness as well as during the different propofol sedation levels as compared to flanker frequencies.

12 months

The change of thalamocortical connectivity mediates the intrinsic alpha frequency-elicited synchronicity changes across modalities (EEG and fMRI)

12 months

Choline concentrations in the occipital cortex will change with propofol sedation

12 months

Intrinsic alpha frequency-elicited synchronicity across modalities (EEG and fMRI) is associated with changes in choline concentrations

12 months

Simultaneous changes of the aperiodic component of EEG with the different levels of propofol sedation: aperiodic activity in EEG is a potential marker of arousal

12 months

Eligibility criteria

Inclusion Criteria: * Female and male healthy individuals (ASA I: assessed according to the American Society of Anesthesiologists Physical Status Classification System a non-acute or chronic disease), non-pregnant, non-smokers, non-drug-users, and presenting no or minimal alcohol use. * Age: 18 to 35 years * Capacity to give consent * Written consent after detailed information. Exclusion criteria: * Individuals who do not meet all inclusion criteria * Previous brain surgery * History of epileptic seizures * History of psychiatric or neurological disease * Physical status other than American Society of Anesthesiologists physical status I, e.g., presence of severe internal or systemic disease * Chronic intake of medication or drugs (Alcohol, Marihuana, Cocaine, Opioids, Benzodiazepine, etc.) * Impaired hearing or presence of deafness * Absence of fluency in the German language * Known disposition to malignant hyperthermia * Previous diagnosis of hepatic porphyria * Body mass index greater than 30 kg/m2 * Gastrointestinal disorders with a disposition for gastroesophageal regurgitation * Known or suspected difficult airway * Known hypersensitivity to propofol or any propofol injectable emulsion components (i.e., eggs, eggs products, soybeans, or soy products) * Atopy/severe allergies/asthma * Cardiological abnormalities: torsades de pointes, prolonged QT interval, QT changes present since birth. * Contraindications to MRI (e.g., pacemakers, artificial heart valves, cardioseal, aneurysm clips, implanted magnetic metal parts (screws, plates from surgery), cochlear implants, metal splitters/grenade splinters, acupuncture needle, insulin pump, piercings that cannot be removed, etc) * Pregnancy * Subjects with claustrophobia

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 35, 'type': 'ESTIMATED'}}

Updated at

2023-12-22

1 organization

Organization

Technical University of Munich