Brain at risk - Towards a better understanding of age-related effects of anesthesia by simultaneous EEG, REG, and MRI markers in long-tailed macaques.

• Applicant: Dr.-Ing. Pablo Martinez-Vazquez, Ph.D.
• Subject Area: Anaesthesiology ; Cognitive, Systems and Behavioural Neurobiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 532728552

Despite the widespread clinical use of general anesthetics from their evident benefit for the patients undergoing surgery, their use has been recognized as a hazardous endeavor with potential adverse effects since the beginning of its modern history. The elderly are among the most susceptible and vulnerable population groups to suffer memory disturbance and other types of postoperative cognitive impairments. The incomplete understanding and detection of anesthetics' adverse mechanisms on brain stress prone to postoperative cognitive deficiencies are major problems. In daily clinical practice, current monitoring systems, based mainly on Electroencephalogram (EEG), only describe the patient´s depth of hypnosis. EEG monitors design followed the depth of anesthesia-concentration (DOA-Ce) approach, which links the estimation of the patient´s depth of hypnosis with the drug concentrations. The DOA-Ce methodology allows tailoring drug administration, reducing intraoperative awareness episodes and excessive concentrations. However, despite the high benefits of this approach, the current understanding and detection of brain stress events and the prevention of postoperative declines is still an unsolved problem. Therefore, it is crucial to find new non-invasive markers related to stress mechanisms, to help practitioners to take proper actions to mitigate potential adverse effects on cognitive function. In that respect, Magnetic Resonance Imaging (MRI) is an excellent companion for searching novel EEG patterns that identify adverse situations. The Rheoencephalography (REG), a continuous non-invasive cerebral-related blood flow properties, also appears as an excellent complement to EEG for brain monitoring during general anesthesia. Our aim is to study, with the help of the long-tail macaque (Macaca fascicularis) model, different oscillatory and temporal EEG and REG properties in relation to MRI under the triad age-concentration-anesthetic type toward deciphering features prone to describe brain stress situations. Starting from constructing a novel tailored setup to register MRI simultaneously with EEG and REG, we propose an extensive controlled experiment with several target randomized concentrations and effects to drive the brain at different anesthesia conditions using two anesthetics, sevoflurane and propofol. From MRI information as our primary reference, we will perform a detailed description of the brain activity from the perspective of the REG and local and global EEG causal cortico-cortical oscillations at different drug rates as well as characterizing locally and globally the EEG burst suppression morphologies at iso-effect conditions elicited under target controlled burst suppression levels. All descriptions will be integrated under different models. We hope to provide new non-invasive insights into the brain state regarding aging, concentration, and anesthetic, allowing future monitoring technologies to reduce adverse postoperative effects.

• DFG Programme: Research Grants
• Co-Investigators: Professorin Dr. Susann Boretius; Dr. Amir Moussavi