Characterizing Alterations in Cortisol Secretion During Cardiac Surgery.

Cortisol is a neuroendocrine hormone of the hypothalamus-pituitary-adrenal (HPA) axis secreted from adrenal glands in response to stimulation by adrenocorticotropic hormone (ACTH) from the anterior pituitary and corticotropin releasing hormone (CRH) from the hypothalamus. Cortisol has multiple functionalities in maintaining bodily homeostasis - including anti-inflammatory influences - through its diurnal secretion pattern (which has been studied extensively); its secretion is also increased in response to major traumatic events such as surgery. Due to the adverse health consequences of an abnormal immune response, it is crucial to understand the effect of cortisol in modulating inflammation. To address this physiological issue, we characterize the secretion of cortisol using a high temporal resolution dataset of ten patients undergoing coronary arterial bypass grafting (CABG) surgery, in comparison with a control group not undergoing surgery. We find that cortisol exhibits different pulsatile dynamics in those undergoing cardiac surgery compared to the control subjects. We also summarize the causality of cortisol's relationship with different cytokines (which are one type of inflammatory markers) by performing Granger causality analysis.Clinical relevance- This work documents time-varying patterns of the HPA axis hormone cortisol in the inflammatory response to cardiac surgery and may eventually help improve patients' prognosis post-surgery (or in other conditions) by enabling early detection of an abnormal cortisol or inflammatory response and enabling patient specific remedial interventions.

Sparse Deconvolution and Causality Analysis of Inflammatory Markers During Cardiac Surgery.

Major bodily trauma such as cardiac surgery elicits (in response to tissue injury and other exogenous surgical factors) a whole-body inflammation response during which specialized signaling proteins called cytokines are synthesized and invoke multiple defense mechanisms. Many proinflammatory and anti-inflammatory cytokines such as interleukins (IL) and tumor necrosis factor (TNF) are produced to initiate bodily repair. Due to the adverse health consequences, including mortality, of a maladaptive cytokine response, understanding their complex dynamics using system-theoretic modeling and analysis may pave the way for controlling the inflammatory response which may eventually improve medical outcomes for patients. To this end, we use clinical data from ten patients undergoing coronary arterial bypass graft surgery to study the response of four cytokines (IL6, IL8, IL10, TNFα) and the neuroendocrine hormone cortisol. We perform deconvolution to obtain the secretory pulses underlying their pulsatile production and analyze causal interactions, mathematically uncovering some interactive relationships found in previous experimental studies.Clinical relevance- This work is a first step towards a mechanistic inference of the inflammatory response to surgery that could eventually help control the inflammatory response and could inform medical interventions to improve patient outcomes.

Olfactory-induced Positive Affect and Autonomic Response as a Function of Hedonic and Intensity Attributes of Fragrances.

Olfactory perception is intrinsically tied to emotional processing, in both behavior and neurophysiology. Despite advances in olfactory-affective neuroscience, it is unclear how separate attributes of odor stimuli contribute to olfactoryinduced emotions, especially within the positive segment of the hedonic dimension to avoid potential cross-valence confounds. In this study, we examined how pleasantness and intensity of fragrances relate to different grades of positive affect. Our results show that greater odor pleasantness and intensity are independently associated with stronger positive affect. Pleasantness has a greater influence than intensity in evoking a positive vs. neutral affect, whereas intensity is more impactful than pleasantness in evoking an extreme positive vs. positive response. Autonomic response, as assessed by the galvanic skin response (GSR) was found to decrease with increasing pleasantness but not intensity. This clarifies how olfactory and affective processing induce significant downstream effects in peripheral physiology and self-reported affective experience, pertinent to the thriving field of olfactory neuromarkerting.

Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach.

OBJECTIVE: Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are complicated medical disorders, with little known etiologies. The purpose of this research is to characterize FMS and CFS by studying the variations in cortisol secretion patterns, timings, amplitudes, the number of underlying pulses, as well as infusion and clearance rates of cortisol. METHODS: Using a physiological state-space model with plausible constraints, we estimate the hormonal secretory events and the physiological system parameters (i.e., infusion and clearance rates). RESULTS: Our results show that the clearance rate of cortisol is lower in FMS patients as compared to their matched healthy individuals based on a simplified cortisol secretion model. Moreover, the number, magnitude, and energy of hormonal secretory events are lower in FMS patients. During early morning hours, the magnitude and energy of the hormonal secretory events are higher in CFS patients. CONCLUSION: Due to lower cortisol clearance rate, there is a higher accumulation of cortisol in FMS patients as compared to their matched healthy subjects. As the FMS patient accumulates higher cortisol residues, internal inhibitory feedback regulates the hormonal secretory events. Therefore, the FMS patients show a lower number, magnitude, and energy of hormonal secretory events. Though CFS patients have the same number of secretory events, they secrete lower quantities during early morning hours. When we compare the results for CFS patients against FMS patients, we observe different cortisol alteration patterns. SIGNIFICANCE: Characterizing CFS and FMS based on the cortisol alteration will help us to develop novel methods for treating these disorders.

A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue.

Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome (CFS) are complex medical conditions with similar symptoms such as anxiety, fatigue, depression, headaches, muscle aches and joint pain. The etiology of both these syndromes is unknown. The objective of this study is to characterize FMS, both in the presence and in the absence of CFS, by analyzing variations in cortisol secretion patterns, timings, amplitudes, and the number of the underlying pulses as well as infusion and clearance rates. The comparison is performed against matched healthy control subjects. We estimate the hormonal secretory events by deconvolving cortisol data using a two-step coordinate descent approach. The first step implements a sparse recovery approach to infer the amplitudes and the timings of the cortisol secretion events from limited cortisol hormone data. The main advantage of this method is estimating the cortisol secretory events using a system theoretic approach. The second step is to estimate the physiological system parameters (i.e. infusion and clearance rates). This approach has been verified on healthy individuals previously. Our results show that the clearance rate of cortisol by the liver is relatively lower in patients as compared to the matched healthy individuals. This suggests that there is a relatively higher accumulation of serum cortisol in patients when compared to matched healthy subjects.

Broad range of neural dynamics from a time-varying FitzHugh-Nagumo model and its spiking threshold estimation.

We study the use of the FitzHugh-Nagumo (FHN) model for capturing neural spiking. The FHN model is a widely used approximation of the Hodgkin-Huxley model that has significant limitations. In particular, it cannot produce the key spiking behavior of bursting. We illustrate that by allowing time-varying parameters for the FHN model, these limitations can be overcome while retaining its low-order complexity. This extension has applications in modeling neural spiking behaviors in the thalamus and the respiratory center. We demonstrate the use of the FHN model from an estimation perspective by presenting a novel parameter estimation method that exploits its multiple time-scale properties, and compare the performance of this method with the extended Kalman filter in several illustrative examples. We demonstrate that the dynamics of the spiking threshold can be recovered even in the absence of complete specifications for the system.