Inferring neural dynamics during burst suppression using a neurophysiology-inspired switching state-space model

Burst suppression is an electroencephalography (EEG) pattern associated with profoundly inactivated brain states characterized by cerebral metabolic depression. Its distinctive feature is alternation between short temporal segments of near-isoelectric inactivity (suppressions) and relatively high-voltage activity (bursts). Prior modeling studies suggest that burst-suppression EEG is a manifestation of two alternating brain states associated with consumption (during a burst) and production (during a suppression) of adenosine triphosphate (ATP). This finding motivates us to infer latent states characterizing alternating brain states and underlying ATP kinetics from instantaneous power of multichannel EEG using a switching state-space model. Our model assumes Gaussian distributed data as a broadcast network manifestation of one of two global brain states. The two brain states are allowed to stochastically alternate with transition probabilities that depend on the instantaneous ATP level, which evolves according to first-order kinetics. The rate constants governing the ATP kinetics are allowed to vary as first-order autoregressive processes. Our latent state estimates are determined from data using a sequential Monte Carlo algorithm. Our neurophysiology-informed model not only provides unsupervised segmentation of multi-channel burst-suppression EEG but can also generate additional insights on the level of brain inactivation during anesthesia.Comment: To appear in the proceedings of the 2020 IEEE Asilomar Conference on Signals, Systems, and Computer

A simulation-based comparative analysis of PID and LQG control for closed-loop anesthesia delivery

Closed loop anesthesia delivery (CLAD) systems can help anesthesiologists efficiently achieve and maintain desired anesthetic depth over an extended period of time. A typical CLAD system would use an anesthetic marker, calculated from physiological signals, as real-time feedback to adjust anesthetic dosage towards achieving a desired set-point of the marker. Since control strategies for CLAD vary across the systems reported in recent literature, a comparative analysis of common control strategies can be useful. For a nonlinear plant model based on well-established models of compartmental pharmacokinetics and sigmoid-Emax pharmacodynamics, we numerically analyze the set-point tracking performance of three output-feedback linear control strategies: proportional-integral-derivative (PID) control, linear quadratic Gaussian (LQG) control, and an LQG with integral action (ILQG). Specifically, we numerically simulate multiple CLAD sessions for the scenario where the plant model parameters are unavailable for a patient and the controller is designed based on a nominal model and controller gains are held constant throughout a session. Based on the numerical analyses performed here, conditioned on our choice of model and controllers, we infer that in terms of accuracy and bias PID control performs better than ILQG which in turn performs better than LQG. In the case of noisy observations, ILQG can be tuned to provide a smoother infusion rate while achieving comparable steady-state response with respect to PID. The numerical analyses framework and findings, reported here, can help CLAD developers in their choice of control strategies. This paper may also serve as a tutorial paper for teaching control theory for CLAD.Comment: Accepted in the IFAC2020 Conferenc

A Smoother State Space Multitaper Spectrogram

A recent work (Kim et al. 2018) has reported a novel statistical modeling framework, the State-Space Multitaper (SSMT) method, to estimate time-varying spectral representation of non-stationary time series data. It combines the strengths of the multitaper spectral (MT) analysis paradigm with that of state-space (SS) models. In this current work, we explore a variant of the original SSMT framework by imposing a smoothness promoting SS model to generate smoother estimates of power spectral densities for non-stationary data. Specifically, we assume that the continuous processes giving rise to observations in the frequencies of interest follow multiple independent Integrated Wiener Processes (IWP). We use both synthetic data and electroencephalography (EEG) data collected from a human subject under anesthesia to compare the IWP-SSMT with the SSMT method and demonstrate the former's utility in yielding smoother descriptions of underlying processes. The original SSMT and IWP-SSMT can co-exist as a part of a model selection toolkit for nonstationary time series data

A hidden semi-Markov model for estimating burst suppression EEG

Burst suppression is an electroencephalogram (EEG) pattern associated with profoundly inactivated brain states characterized by cerebral metabolic depression. This pattern is distinguished by short-duration band-limited electrical activity (bursts) interspersed between relatively near-isoelectric periods (suppressions). Prior work in neurophysiology suggests that burst and suppression segments are respectively associated with consumption and regeneration of adenosine triphosphate resource in cortical networks. This indicates that once a suppression (or, burst) segment begins, the propensity to switch out of the state gradually increases with duration spent in the state. Prior EEG monitoring frameworks that track the brain state during burst suppression by tracking the estimated fraction of time spent in suppression, relative to bursts, do not incorporate this information. In this work, we incorporate this information within a hidden semi-Markov model (HSMM) wherein two states (burst & suppression) stochastically switch between each other using sojourn-time dependent transition probabilities. We demonstrate the HSMM's utility in analyzing clinical data by estimating the state probabilities, the optimal state sequence, and the brain's metabolic activation level characterized by parameters governing sojourn-time dependence in transition probabilities. The HSMM-based approach proposed here provides a novel statistical framework that advances the state-of-the-art in analyzing burst suppression EEG

Turkish Tale

Oral narrative of a Turkish folktale collected by Professor Ahmet Edip Uysal, Dr. Waren Walker and Barbara Walker (Mrs. Warren Walker). Each narrative was translated into English by native Turkish speakers (mostly students), paid for by the Walkers, who then edited the translations

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). Pharmacoki-netic/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.National Institutes of Health (U.S.) (Grant R01-GM104948)National Institutes of Health (U.S.) (Grant P01-GM118629

Constructing a control-ready model of EEG signal during general anesthesia in humans

Significant effort toward the automation of general anesthesia has been made in the past decade. One open challenge is in the development of control-ready patient models for closed-loop anesthesia delivery. Standard depth-of-anesthesia tracking does not readily capture inter-individual differences in response to anesthetics, especially those due to age, and does not aim to predict a relationship between a control input (infused anesthetic dose) and system state (commonly, a function of electroencephalography (EEG) signal). In this work, we developed a control-ready patient model for closed-loop propofol-induced anesthesia using data recorded during a clinical study of EEG during general anesthesia in ten healthy volunteers. We used principal component analysis to identify the low-dimensional state-space in which EEG signal evolves during anesthesia delivery. We parameterized the response of the EEG signal to changes in propofol target-site concentration using logistic models. We note that inter-individual differences in anesthetic sensitivity may be captured by varying a constant cofactor of the predicted effect-site concentration. We linked the EEG dose-response with the control input using a pharmacokinetic model. Finally, we present a simple nonlinear model predictive control in silico demonstration of how such a closed-loop system would work

Perioperative Electroencephalogram Spectral Dynamics Related to Postoperative Delirium in Older Patients

BACKGROUND: Intraoperative electroencephalography (EEG) signatures related to the development of postoperative delirium (POD) in older patients are frequently studied. However, a broad analysis of the EEG dynamics including preoperative, postinduction, intraoperative and postoperative scenarios and its correlation to POD development is still lacking. We explored the relationship between perioperative EEG spectra-derived parameters and POD development, aiming to ascertain the diagnostic utility of these parameters to detect patients developing POD. METHODS: Patients aged ≥65 years undergoing elective surgeries that were expected to last more than 60 minutes were included in this prospective, observational single center study (Biomarker Development for Postoperative Cognitive Impairment [BioCog] study). Frontal EEGs were recorded, starting before induction of anesthesia and lasting until recovery of consciousness. EEG data were analyzed based on raw EEG files and downloaded excel data files. We performed multitaper spectral analyses of relevant EEG epochs and further used multitaper spectral estimate to calculate a corresponding spectral parameter. POD assessments were performed twice daily up to the seventh postoperative day. Our primary aim was to analyze the relation between the perioperative spectral edge frequency (SEF) and the development of POD. RESULTS: Of the 237 included patients, 41 (17%) patients developed POD. The preoperative EEG in POD patients was associated with lower values in both SEF (POD 13.1 ± 4.6 Hz versus no postoperative delirium [NoPOD] 17.4 ± 6.9 Hz; P = .002) and corresponding γ-band power (POD -24.33 ± 2.8 dB versus NoPOD -17.9 ± 4.81 dB), as well as reduced postinduction absolute α-band power (POD -7.37 ± 4.52 dB versus NoPOD -5 ± 5.03 dB). The ratio of SEF from the preoperative to postinduction state (SEF ratio) was ~1 in POD patients, whereas NoPOD patients showed a SEF ratio >1, thus indicating a slowing of EEG with loss of unconscious. Preoperative SEF, preoperative γ-band power, and SEF ratio were independently associated with POD (P = .025; odds ratio [OR] = 0.892, 95% confidence interval [CI], 0.808-0.986; P = .029; OR = 0.568, 95% CI, 0.342-0.944; and P = .009; OR = 0.108, 95% CI, 0.021-0.568, respectively). CONCLUSIONS: Lower preoperative SEF, absence of slowing in EEG while transitioning from preoperative state to unconscious state, and lower EEG power in relevant frequency bands in both these states are related to POD development. These findings may suggest an underlying pathophysiology and might be used as EEG-based marker for early identification of patients at risk to develop POD