AnesthesiaNCT06179719
EEG-fMRI Experiments During Anesthesia Induction With Propofol
A study testing Propofol and visual flickering stimulation at the alpha frequency in people with Anesthesia, run by Technical University of Munich at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Anesthesia
- What is being tested?
- Propofol and visual flickering stimulation at the alpha frequency
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesGermany
- Study dates
- 10 Sep 2023to 10 Sep 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.)
Show all 19Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Germany2 sites, 2 recruiting
- Recruiting
Technische Universität München
München, München (Stadt), 80686
Juliana Zimmermann, MD. Ph.D., +49 89 4140 8681, juliana.zimmermann@tum.de
Gerhard Schneider, Prof. Dr. med.
- Recruiting
Klinikum rechts der Isar - Klinik für Anästhesiologie und Intensivmedizin
Munich, Bavaria, 81675
Central contact Anesthesiology and Intensive Care Medicine, +49 89 4140 4291, AINS@mri.tum.de
About this study
Official title: Simultaneous EEG-fMRI Study in Healthy Humans During Induction of Propofol Anesthesia to Investigate the Dynamics of Thalamocortical Functional Connectivity in the Alpha Frequency
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.
Read the detailed description
This study aims to investigate healthy cortical and subcortical neural processes during induction of general anesthesia with propofol, which is clinically relevant for postoperative delirium, a common cognitive disorder, after surgical intervention in the elderly.
Intrinsic neural oscillations within the alpha frequency band (~8-13Hz) can be measured with the EEG, showing the highest power (i.e., amplitude) in occipital electrodes during eyes-closed wakefulness resting state. Under general anesthesia, especially with propofol, the power of these oscillations decreases in the occipital cortex but increases in the frontal cortex. Although neither the exact mechanisms underlying the generation of alpha oscillations nor their dynamics under anesthesia are entirely understood, it has been suggested that the thalamus might be a key player modulating the shift of alpha-band power throughout the brain.
Post-operative delirium (POD) is a complication after a surgical intervention characterized by an acute impairment of consciousness, attention, and arousal with a fluctuating evolution. This is prevalent mainly in elderly patients, especially in those with pre-existing neurocognitive disorders, neurodegenerative disease, and those undergoing complex or emergency procedures. Despite the functional and economic burden this disorder places on the patient and the health system, e.g., it increases hospital stay and risk of mortality, treatment options and risk management strategies are still limited. Several of our previous studies and those from other groups have highlighted the link between alpha oscillations and clinical outcomes related to POD. For instance, low frontal alpha power - both during maintenance and emergence from general anesthesia - is associated with a higher risk of POD. Low frontal alpha power is also associated with pre-operative neurocognitive impairment, a well-described risk factor for POD. The biochemical nature of this association is still unknown; the role of the cholinergic system as a mediator has been suggested.
Therefore, a better understanding of the mechanisms underlying the generation of alpha oscillations and their dynamics under general anesthesia could open new doors to diagnostic and treatment options for POD.
Based on our past EEG-fMRI experiments in healthy subjects applying visual stimulation at the alpha frequency, the investigators have shown that (i) visual stimulation using a rhythmic flickering light at a specific frequency evokes a reliable response in the occipital brain, which can be measured with EEG and functional resonance magnetic imaging (fMRI), (ii) the response to this stimulation can be evaluated via evoked potential/power/coherence analyses (EEG) or functional connectivity analyses (fMRI), and (iii) visual flicker stimulation at/near to a subject's intrinsic alpha frequency, known as the 'individual alpha frequency' (IAF), generates a response within brain areas beyond the occipital cortex, such as frontal and parietal regions and most importantly, the thalamus, suggesting an interaction with - and a method to assess - intrinsic alpha oscillations.
The investigators propose a simultaneous EEG-fMRI study in which young, healthy participants, anesthetized with propofol, are presented with a visual flicker stimulation paradigm at/around the participant's IAF. Our experimental design includes recordings before the participant is anesthetized (wakefulness pre-anesthesia) and during three different anesthesia concentrations (low, mid, and deep). Functional magnetic resonance spectroscopy will be acquired during resting state throughout all states. A wakefulness post-anesthesia recording in resting state without stimulation is also planned. This approach has several advantages. For instance, the simultaneous acquisition makes it possible to correlate the dynamics of alpha oscillations measured by EEG while having access to a whole-brain resolution via fMRI, including subcortical areas like the thalamus. This is relevant to understanding the interaction between cortical and subcortical neural processes generating alpha oscillations.
Furthermore, it exploits the fact that our modality of stimulation at the IAF enhances intrinsic alpha processes, which can potentially become a treatment to reduce the risk of POD under anesthesia. Furthermore, by acquiring functional spectroscopy data, the investigators can detect biochemical changes in the brain during each state. Finally, our experimental design enables, first, a chronologic follow-up of alpha dynamics during the induction of propofol anesthesia, and second, by acquiring data after the intervention, investigators will have an immediate control to contrast before and after anesthesia.
For our participant's safety, propofol anesthesia will be titrated until deep concentrations without eliciting a burst suppression state, avoiding intubation and artificial respiration support.
This study represents an essential step towards understanding alpha oscillatory processes in the awake and anesthetized brain relevant to the future development of potential preventative/treatment options for POD.
- Conditions
- Anesthesia
- Being tested
- Propofol, visual flickering stimulation at the alpha frequency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
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).
visual flickering stimulation at the alpha frequencyBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Experimental | Not described Receives: Drug: Propofol; Behavioral: visual flickering stimulation at the alpha frequency |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
About a decade ago, a novel mechanism explaining how the brain clears out waste products was postulated (Iliff et al., 2012). This is known as the 'glymphatic hypothesis', and it consists of the transportation of waste products from the brain parenchyma to the periphery facilitated by a continuous circulation of cerebral spinal fluid (CSF flow) throughout the brain (Habilitz \& Nedergaad 2021). One driving mechanism of this continuous flow of CSF is global brain activity. The investigators aim to study the effect of propofol anesthesia on the correlation between the global grey matter BOLD and CSF flow signal derived from resting-state fMRI measurements. This idea comes from recent high-impact publications showing first, that during deep sleep, these two signals are highly coupled (Fultz et al., 2019), and second, that this coupling is reduced during neuropsychiatric diseases such as Alzheimer's disease (Han et al., 2021).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2023
- Study start10 Sep 2023
- Primary completion10 Sep 2024 (estimated)
- Study completion10 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06179719
- Sponsor's protocol ID
- PropofolStudyTUM2023
- Status last verified
- Sep 2023
- First submitted
- 23 Nov 2023
- Last updated
- 22 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 22896675Hablitz 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.
PubMed 34526407Fultz 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.
PubMed 31672896Han 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.
PubMed 34061820
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Simultaneous EEG-fMRI Study in Healthy Humans During Induction of Propofol Anesthesia to Investigate the Dynamics of Thalamocortical Functional Connectivity in the Alpha Frequency
- ClinicalTrials.gov ID
- NCT06179719
- Acronym / sponsor ID
- PropofolStudyTUM2023
- Conditions
- Anesthesia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Study start
- 10 Sep 2023 (actual)
- Primary completion
- 10 Sep 2024 (estimated)
- Study completion
- 10 Sep 2026 (estimated)
- First posted
- 22 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study aims to investigate healthy cortical and subcortical neural processes during induction of general anesthesia with propofol, which is clinically relevant for postoperative delirium, a common cognitive disorder, after surgical intervention in the elderly.
Intrinsic neural oscillations within the alpha frequency band (~8-13Hz) can be measured with the EEG, showing the highest power (i.e., amplitude) in occipital electrodes during eyes-closed wakefulness resting state. Under general anesthesia, especially with propofol, the power of these oscillations decreases in the occipital cortex but increases in the frontal cortex. Although neither the exact mechanisms underlying the generation of alpha oscillations nor their dynamics under anesthesia are entirely understood, it has been suggested that the thalamus might be a key player modulating the shift of alpha-band power throughout the brain.
Post-operative delirium (POD) is a complication after a surgical intervention characterized by an acute impairment of consciousness, attention, and arousal with a fluctuating evolution. This is prevalent mainly in elderly patients, especially in those with pre-existing neurocognitive disorders, neurodegenerative disease, and those undergoing complex or emergency procedures. Despite the functional and economic burden this disorder places on the patient and the health system, e.g., it increases hospital stay and risk of mortality, treatment options and risk management strategies are still limited. Several of our previous studies and those from other groups have highlighted the link between alpha oscillations and clinical outcomes related to POD. For instance, low frontal alpha power - both during maintenance and emergence from general anesthesia - is associated with a higher risk of POD. Low frontal alpha power is also associated with pre-operative neurocognitive impairment, a well-described risk factor for POD. The biochemical nature of this association is still unknown; the role of the cholinergic system as a mediator has been suggested.
Therefore, a better understanding of the mechanisms underlying the generation of alpha oscillations and their dynamics under general anesthesia could open new doors to diagnostic and treatment options for POD.
Based on our past EEG-fMRI experiments in healthy subjects applying visual stimulation at the alpha frequency, the investigators have shown that (i) visual stimulation using a rhythmic flickering light at a specific frequency evokes a reliable response in the occipital brain, which can be measured with EEG and functional resonance magnetic imaging (fMRI), (ii) the response to this stimulation can be evaluated via evoked potential/power/coherence analyses (EEG) or functional connectivity analyses (fMRI), and (iii) visual flicker stimulation at/near to a subject's intrinsic alpha frequency, known as the 'individual alpha frequency' (IAF), generates a response within brain areas beyond the occipital cortex, such as frontal and parietal regions and most importantly, the thalamus, suggesting an interaction with - and a method to assess - intrinsic alpha oscillations.
The investigators propose a simultaneous EEG-fMRI study in which young, healthy participants, anesthetized with propofol, are presented with a visual flicker stimulation paradigm at/around the participant's IAF. Our experimental design includes recordings before the participant is anesthetized (wakefulness pre-anesthesia) and during three different anesthesia concentrations (low, mid, and deep). Functional magnetic resonance spectroscopy will be acquired during resting state throughout all states. A wakefulness post-anesthesia recording in resting state without stimulation is also planned. This approach has several advantages. For instance, the simultaneous acquisition makes it possible to correlate the dynamics of alpha oscillations measured by EEG while having access to a whole-brain resolution via fMRI, including subcortical areas like the thalamus. This is relevant to understanding the interaction between cortical and subcortical neural processes generating alpha oscillations.
Furthermore, it exploits the fact that our modality of stimulation at the IAF enhances intrinsic alpha processes, which can potentially become a treatment to reduce the risk of POD under anesthesia. Furthermore, by acquiring functional spectroscopy data, the investigators can detect biochemical changes in the brain during each state. Finally, our experimental design enables, first, a chronologic follow-up of alpha dynamics during the induction of propofol anesthesia, and second, by acquiring data after the intervention, investigators will have an immediate control to contrast before and after anesthesia.
For our participant's safety, propofol anesthesia will be titrated until deep concentrations without eliciting a burst suppression state, avoiding intubation and artificial respiration support.
This study represents an essential step towards understanding alpha oscillatory processes in the awake and anesthetized brain relevant to the future development of potential preventative/treatment options for POD.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | Experimental | Drug: Propofol, Behavioral: visual flickering stimulation at the alpha frequency |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropofolAnesthesia 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). | Drug | Healthy controls |
| visual flickering stimulation at the alpha frequencyParticipants 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. | Behavioural | Healthy controls |
Primary outcome
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.
Time frame: 12 months
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.
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.
Time frame: 12 months
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.
The change of thalamocortical connectivity mediates the intrinsic alpha frequency-elicited synchronicity changes across modalities (EEG and fMRI)
Time frame: 12 months
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.
Choline concentrations in the occipital cortex will change with propofol sedation
Time frame: 12 months
The investigators expect choline concentration in the occipital cortex to change with increasing concentrations of propofol sedation.
Intrinsic alpha frequency-elicited synchronicity across modalities (EEG and fMRI) is associated with changes in choline concentrations
Time frame: 12 months
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.
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
Time frame: 12 months
The investigators hypothesize that the slope of the aperiodic 1/f distribution will change with increasing levels of propofol sedation across subjects.
1 secondary outcome
Propofol sedation changes the correlation between the global grey matter fMRI blood oxygen level dependent (BOLD) and CSF flow signals.
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2023.
- Background: PubMed 22896675Iliff 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.
- Background: PubMed 34526407Hablitz 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.
- Background: PubMed 31672896Fultz 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.
- Background: PubMed 34061820Han 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.
Related trials for Anesthesia
RecruitingObservational study
Anesthetic Technique and Quality of Recovery After Cesarean Delivery
Ceserean Section, Obstetric Quality of Recovery
Not yet recruiting
Dural Puncture Epidural With 27G vs 26G Needles Versus Standard Epidural for Elective Cesarean Delivery
Cesarean Section, Anesthesia, Obstetrical
Not yet recruiting
Monitored Anesthesia Care and Soft Tissue Infiltration With Local Anesthesia Feasibility Trial
Hip Fracture Surgeries, Intertrochanteric Fracture
Active, not recruiting
Comparison of Prophylactic Continuous Infusion of Norepinephrine, Ephedrine, and Their Combination for Prevention of Hypotension During Spinal Anaesthesia for Caesarean Delivery
Maternal Hypotension After Spinal Anesthesia
RecruitingPhase 4
The Electroencephalographic Mechanisms of Anesthesia and Human Consciousness
Consciousness, Level Altered
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klinikum rechts der Isar - Klinik für Anästhesiologie und Intensivmedizin
Munich, Germany
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Propofol and visual flickering stimulation at the alpha frequency in people with Anesthesia, run by Technical University of Munich at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06179719, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2023.