EEG-fMRI Experiments During Anesthesia Induction With Propofol

NCT06179719 | Recruiting

• 1 other identifier: PropofolStudyTUM2023
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (6)

• 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.

  Before propofol sedation administration during resting eyes closed baseline recordings and during the different propofol sedation levels, the investigators expect to see changes in EEG-based oscillatory responses to visual flicker stimulation at the baseline intrinsic alpha frequency compared to control flanker frequencies. These changes imply an interaction between the intrinsic alpha oscillations and the flicker stimulation.

  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.

  During resting baseline conditions (i.e., before propofol sedation administration), the investigators expect a change of functional connectivity between occipitoparietal areas and the thalamus as well as in connectivity between occipitoparietal areas as well as the thalamus and frontal brain areas. With increasing propofol sedation, the investigators expect this selective change in connectivity to intrinsic alpha frequency flicker versus flanker frequencies to diminish.

  12 months

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

  Concurrent analysis of EEG and fMRI: During resting baseline conditions (i.e., before propofol sedation administration), the investigators expect the phase coupling based on imaginary coherence of alpha oscillations to covary with functional connectivity from fMRI for intrinsic alpha frequency flicker across stimulation repetitions. The investigators expect the supporting brain regions of covarying connectivity across modalities to be centered in the thalamus. With increasing propofol sedation (going from low, mid until high propofol level measured by MOAAS), the investigators expect this cross-modality covariation of connectivity measures for intrinsic alpha frequency flicker frequencies to change.

  12 months

• Choline concentrations in the occipital cortex will change with propofol sedation

  The investigators expect choline concentration in the occipital cortex to change with increasing concentrations of propofol sedation.

  12 months

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

  Integration of derived measures: The investigators expect both phase coupling of alpha oscillations from EEG as well as changes in thalamocortical functional connectivity in response to visual flicker stimulation at the intrinsic alpha frequency to correlate with changes in choline concentrations measured by Spectroscopy in the occipital cortex.

  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

  The investigators hypothesize that the slope of the aperiodic 1/f distribution will change with increasing levels of propofol sedation across subjects.

  12 months

Secondary Outcomes (1)

• Propofol sedation changes the correlation between the global grey matter fMRI blood oxygen level dependent (BOLD) and CSF flow signals.

  12 months

Study Arms (1)

Healthy controls

EXPERIMENTAL

Drug: Propofol; Behavioral: visual flickering stimulation at the alpha frequency

Interventions

Propofol DRUG

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).

Healthy controls

visual flickering stimulation at the alpha frequency BEHAVIORAL

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.

Healthy controls

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Technical University of Munich: lead

Study Sites (2)

Klinikum rechts der Isar - Klinik für Anästhesiologie und Intensivmedizin

Munich, Bavaria, 81675, Germany

RECRUITING

Technische Universität München

München, München (Stadt), 80686, Germany

RECRUITING

Related Publications (4)

• Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012 Aug 15;4(147):147ra111. doi: 10.1126/scitranslmed.3003748.

  PMID: 22896675 BACKGROUND

• Hablitz LM, Nedergaard M. The Glymphatic System: A Novel Component of Fundamental Neurobiology. J Neurosci. 2021 Sep 15;41(37):7698-7711. doi: 10.1523/JNEUROSCI.0619-21.2021.

  PMID: 34526407 BACKGROUND

• Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR, Lewis LD. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science. 2019 Nov 1;366(6465):628-631. doi: 10.1126/science.aax5440.

  PMID: 31672896 BACKGROUND

• Han F, Chen J, Belkin-Rosen A, Gu Y, Luo L, Buxton OM, Liu X; Alzheimer's Disease Neuroimaging Initiative. Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology. PLoS Biol. 2021 Jun 1;19(6):e3001233. doi: 10.1371/journal.pbio.3001233. eCollection 2021 Jun.

  PMID: 34061820 BACKGROUND

MeSH Terms

Interventions

Propofol

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2023
• First Posted: December 22, 2023
• Study Start: September 10, 2023
• Primary Completion: September 10, 2024
• Study Completion (Estimated): September 10, 2026
• Last Updated: December 22, 2023

Record last verified: 2023-09

Locations

DE (2)