Simultaneous EEG-fMRI Study in Healthy Humans During Induction of Propofol Anesthesia to Investigate the Dynamics of Thalamocortical Functional Connectivity in the Alpha Frequency
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Healthy controls
干预措施: Propofol (Drug)
Healthy controls
干预措施: visual flickering stimulation at the alpha frequency (Behavioral)
结局指标
主要结局
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.
时间窗: 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.
Choline concentrations in the occipital cortex will change with propofol sedation
时间窗: 12 months
The investigators expect choline concentration in the occipital cortex to change with increasing concentrations of propofol sedation.
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.
时间窗: 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.
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
时间窗: 12 months
The investigators hypothesize that the slope of the aperiodic 1/f distribution will change with increasing levels of propofol sedation across subjects.
The change of thalamocortical connectivity mediates the intrinsic alpha frequency-elicited synchronicity changes across modalities (EEG and fMRI)
时间窗: 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.
Intrinsic alpha frequency-elicited synchronicity across modalities (EEG and fMRI) is associated with changes in choline concentrations
时间窗: 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.
次要结局
- Propofol sedation changes the correlation between the global grey matter fMRI blood oxygen level dependent (BOLD) and CSF flow signals.(12 months)