Influence of midazolam premedication on intraoperative EEG signatures in elderly patients.

OBJECTIVE: To investigate the influence of midazolam premedication on the EEG-spectrum before and during general anesthesia in elderly patients. METHODS: Patients aged ≥65 years, undergoing elective surgery were included in this prospective observational study. A continuous pre- and intraoperative frontal EEG was recorded in patients who received premedication with midazolam (Mid, n = 15) and patients who did not (noMid, n = 30). Absolute power within the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-25 Hz) frequency-bands was analyzed in EEG-sections before (pre-induction), and after induction of anesthesia with propofol (post-induction), as well as during general anesthesia with either propofol or volatile-anesthetics (intra-operative). RESULTS: Pre-induction, α-power of Mid patients was lower compared with noMid-patients (α-power: Mid: -10.75 dB vs. noMid: -9.20 dB; p = 0.036). After induction of anesthesia Mid-patients displayed a stronger increase of frontal α-power resulting in higher absolute α-power at post-induction state, (α-power: Mid -3.56 dB vs. noMid: -6.69 dB; p = 0.004), which remained higher intraoperatively (α-power: Mid: -2.12 dB vs. noMid: -6.10 dB; p = 0.024). CONCLUSION: Midazolam premedication alters the intraoperative EEG-spectrum in elderly patients. SIGNIFICANCE: This finding provides further evidence for the role of GABAergic activation in the induction of elevated, frontal α-power during general anesthesia. TRIAL REGISTRY NUMBER: NCT02265263. 23 September 2014. Principal investigator: Prof. Dr. med. Claudia Spies. (https://clinicaltrials.gov/ct2/show/NCT02265263).

Neural Dynamics of Autistic Repetitive Behaviors and Fragile X Syndrome: Basal Ganglia Movement Gating and mGluR-Modulated Adaptively Timed Learning.

This article develops the iSTART neural model that proposes how specific imbalances in cognitive, emotional, timing, and motor processes that involve brain regions like prefrontal cortex, temporal cortex, amygdala, hypothalamus, hippocampus, and cerebellum may interact together to cause behavioral symptoms of autism. These imbalances include underaroused emotional depression in the amygdala/hypothalamus, learning of hyperspecific recognition categories that help to cause narrowly focused attention in temporal and prefrontal cortices, and breakdowns of adaptively timed motivated attention and motor circuits in the hippocampus and cerebellum. The article expands the model's explanatory range by, first, explaining recent data about Fragile X syndrome (FXS), mGluR, and trace conditioning; and, second, by explaining distinct causes of stereotyped behaviors in individuals with autism. Some of these stereotyped behaviors, such as an insistence on sameness and circumscribed interests, may result from imbalances in the cognitive and emotional circuits that iSTART models. These behaviors may be ameliorated by operant conditioning methods. Other stereotyped behaviors, such as repetitive motor behaviors, may result from imbalances in how the direct and indirect pathways of the basal ganglia open or close movement gates, respectively. These repetitive behaviors may be ameliorated by drugs that augment D2 dopamine receptor responses or reduce D1 dopamine receptor responses. The article also notes the ubiquitous role of gating by basal ganglia loops in regulating all the functions that iSTART models.

Pharmacodynamic modeling of propofol-induced general anesthesia in young adults.

Target controlled infusion (TCI) of intraveneous anesthetics can assist clinical practitioners to provide improved care for General Anesthesia (GA). Pharmacokinetic/Pharmacodynamic (PK/PD) models help in relating the anesthetic drug infusion to observed brain activity inferred from electroencephalogram (EEG) signals. The parameters in popular population PK/PD models for propofol-induced GA (Marsh and Schnider models) are either verified based on proprietary functions of the EEG signal which are difficult to correlate with the neurophysiological models of anesthesia, or the marker itself needs to be estimated simultaneously with the PD model. Both these factors make these existing paradigms challenging to apply in real-time context where a patient-specific tuning of parameters is desired. In this work, we propose a simpler EEG marker from frequency domain description of EEG and develop two corresponding PK/PD modeling approaches which differ in whether they use existing population-level PK models (approach 1) or not (approach 2). We use a simple deterministic parameter estimation approach to identify the unknown PK/PD model parameters from an existing human EEG data-set. We infer that both approaches 1 and 2 yield similar and reasonably good fits to the marker data. This work can be useful in developing patient-specific TCI strategies to induce GA.