![Page 1: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/1.jpg)
Homeostasis Revisited in the Genesis of Stress Reactivity
Pedram Ataee
Supervisors: Drs. G. Dumont, M. Ansermino, T. Boyce and H. NoubariDepartment of Electrical and Computer Engineering
University of British Columbia
June 9, 2013
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 1 / 31
![Page 2: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/2.jpg)
Overview
1 Introduction
2 Mathematical Modelling
3 Parameter Identification
4 Stability Analysis
5 Artificial Bionic Baroreflex
6 Summary and Conclusion
7 Future Work
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 2 / 31
![Page 3: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/3.jpg)
Introduction
Theorem
Early development of mental and physical health problems in adults isassociated with an exaggerated autonomic-cardiac reactivity duringindividual’s childhood [Boyce2001].
Problem Statement
The purpose of this study is to investigate a potential autocatalytic loop(also referred as a positive feedback) leading to an exaggeratedautonomic-cardiac reactivity.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 3 / 31
![Page 4: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/4.jpg)
Introduction
Our Approach
We have decided
to develop a mathematical model for the autonomic-cardiacregulation,
to estimate the time-varying subject-specific model parameters foreach individual,
to create a systematic framework to investigate a potential positivefeedback.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 4 / 31
![Page 5: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/5.jpg)
Introduction
Challenges
Mathematical Modelling: physiology-based scheme, accuratemodelling, and minimal complexity
Parameter Identification: sensitivity, repeatability, and physiologicalconsistency as well as time-varying and subject-specific modelparameters
Stability Analysis: delayed- and nonlinear differential equation modelas well as a numerical indicator of the stability margin
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 5 / 31
![Page 6: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/6.jpg)
Autonomic-Cardiac Regulation (Schematic Diagram)
Figure: Schematic diagram of the autonomic-cardiac regulation model.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 6 / 31
![Page 7: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/7.jpg)
Autonomic-Cardiac Regulation (Mathematical Model)
H(t) =βHTs
1 + γ Tp− VHTp + δH
(
H0 − H(t))
P(t) = −P(t)
R0a (1 + αTs)Ca
+H(t)∆V
Ca
.
Baroreflex
Ts = 1− σ(
P(t − τ))
and Tp = σ(
P(t))
are sympathetic modulatingfunction and parasympathetic modulating function respectively, generatedby the baroreflex control mechanism.
σ(P) = Tmin +Tmax − Tmin
1 + e−αsp(P−Psp)50 ≤ P ≤ 200.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 7 / 31
![Page 8: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/8.jpg)
Autonomic-Cardiac Regulation
H(t) =βHTs
1 + γ Tp
− VHTp + δH(
H0 − H(t))
P(t) = −P(t)
R0a (1 + αTs)Ca
+H(t)∆V
Ca
.
Table: Model parameters of autonomic-cardiac regulation.
Parameter Definition Nominal ValueCa arterial compliance 1.55 mlmmHg−1
R0a minimum arterial resistance 0.6 mmHgsml−1
∆V stroke volume 50 mlH0 intrinsic heart rate 100 min−1
τ sympathetic delay 3 sVH vagal tone 1.17 s−2
βH sympathetic control of HR 0.84 s−2
α sympathetic effect on Ra 1.3γ vagal damping of βH 0.2δH relaxation time 1.7 s−1
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 8 / 31
![Page 9: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/9.jpg)
Autonomic-Cardiorespiratory Regulation
Figure: Schematic diagram of interactions between cardiovascular, respiratory andnervous systems.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 9 / 31
![Page 10: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/10.jpg)
Autonomic-Cardiorespiratory Regulation
Table: Respiration system impacts on VL, HR, VR, and ∆V .
Spontaneous MechanicalInhale Exhale Inhale Exhale
VL (Instantaneous Lung Volume) ↑ ↓ ↑ ↓
HR (Heart Rate) ↑ ↓ ↑ ↓
VR (Venous Return) ↑ ↓ ↓ ↑
∆V (Stroke Volume) ↑ ↓ ↓ ↑
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 10 / 31
![Page 11: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/11.jpg)
Autonomic-Cardiorespiratoy Regulation
Blood Pressure (+Mechnical Coupling: Intrathoracic pressure)
P(t) = −P(t)
R0a (1 + αTs)Ca
+H(t)(∆V±k2VL)
Ca
.
Heart Rate (+Neuromeachnical Coupling: Lung Stretch Reflex)
H(t) =βHTs
1 + γ Tp
− (VH−k1VL)Tp + δH(
H0 − H(t))
Respiration Rate (Chemoreflex)
R(t) = k3
[
(
1 + σco2)
R0 − R(t)]
+ u(t)
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 11 / 31
![Page 12: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/12.jpg)
Autonomic-Cardiorespiratory Regulation
Figure: Neuromechanical couplingeffects of respiration on HR and BP.
Figure: Mechanical coupling effects ofrespiration on HR and BP.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 12 / 31
![Page 13: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/13.jpg)
Parameter Identification (Sensitivity Analysis)
Traditional Analysis
SX (t, µj) =
∣
∣
∣
∣
X (t, µj)− X (t, µj ,0)
µj − µj ,0
∣
∣
∣
∣
×µj
X (t, µj)X = H,P
Aggregation
S(t, µj) =SH(t, µj) + SP(t, µj)
2,
Sj(t) =
√
√
√
√
√
32µj,0∑
µj=12µj,0
S2 (t, µj),
Overall Sensitivity
Sj =
√
√
√
√
tfinal∑
tinitial
S2j (t).
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 13 / 31
![Page 14: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/14.jpg)
Sensitivity Analysis
Figure: The overall sensitivity (mean and standard deviation) of autonomic-cardiacmodel parameters over 100 sensitivity analysis runs with nominal values selected from+/-20% the associated nominal values introduced in 1.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 14 / 31
![Page 15: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/15.jpg)
Sensitivity Analysis
Table: Sensitivity-based parameter classification.
High-sensitivity Low-sensitivity Invariant
Psp γ H0
∆V Ca R0a
VH τ
βH αsp
α δH
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 15 / 31
![Page 16: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/16.jpg)
Parameter Identification
J =EP + EH
2; EX =
n∑
t=0
∣
∣
∣
∣
Xs(t,M)− Xm(t)
Xm(t)
∣
∣
∣
∣
,
Experimental results from a MIMIC data (Case No.: 476).
Figure: Measured vs. model-estimatedsignals: BP, HR, and CO.
Figure: Identification results: αTs , βHTs ,and VHTp .
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 16 / 31
![Page 17: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/17.jpg)
Parameter Identification (Tilt test)
Figure: Subject I
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 17 / 31
![Page 18: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/18.jpg)
Stability Analysis
Delay-Free Realization
X (t) = P(t − τ) + P(t)L⇒ X (s) =
2P(s)
1 + τ2 s
⇒ X (t) =2
τ
[
2P(t)− X (t)]
Equilibrium States
W(t) =
H(t)
P(t)
X (t)
=
f1(
H(t),P(t),X (t))
f2(
H(t),P(t),X (t))
f3(
H(t),P(t),X (t))
, W(t) = 03×1
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 18 / 31
![Page 19: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/19.jpg)
Stability Anlaysis
Lyapunov Analysis
JJJ(Wf ) =∂(f1, f2, f3)
∂(H,P ,X )
∣
∣
∣
∣
Wf
=
∂f1
∂H
∂f1
∂P
∂f1
∂X
∂f2
∂H
∂f2
∂P
∂f2
∂X
∂f3
∂H
∂f3
∂P
∂f3
∂X
W=Wf
Stability Measure (Lyapunov)
Sm = maxi=1,2,3
[
real(λi )]
Stability Measure (Empirical)
Sp =
30∑
t=1
∣
∣
∣P(t)− P(t)
∣
∣
∣
P(t)
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 19 / 31
![Page 20: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/20.jpg)
Stability Analysis
(a) A normal condition with stress (b) A normal condition without stress
Figure: Two metrics for stability margin Sm and Sp over changes of a model parameter from50% to 200% of its nominal value for a healthy physiological condition with (i.e., a 50% lowerVH , and 100% higher βH and α comparing to their nominal values) and without (i.e., VH , βH
and α were fixed at their nominal values) stress. Sm : blue solid line, Sp: green dashed line.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 20 / 31
![Page 21: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/21.jpg)
Stability Anlaysis
Figure: Stability indices Sm over 2-D parameter spaces from 50% to 150% of theirnominal values for a normal physiological condition. The quantitative stability marginmetric Sm at each point of the 2-D parameter space is mapped into a pixel-intensitylevel. A higher pixel-intensity level is related to lower stability margin, and vice versa.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 21 / 31
![Page 22: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/22.jpg)
Autonomic-Cardiac Regulation
Figure: Schematic model of autonomic-cardiac regulation.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 22 / 31
![Page 23: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/23.jpg)
Artificial Bionic Baroreflex
Figure: Schematic model of an artificial bionic baroreflex.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 23 / 31
![Page 24: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/24.jpg)
Artificial Bionic Baroreflex
Figure: Schematic model of the proposed artificial bionic baroreflex.
P0 Adjustment
P0(t +∆) = P0(t) + k · (BPm − BPsp)
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 24 / 31
![Page 25: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/25.jpg)
Subject-Specific Mathematical Model
Table: Individualized nominal values of high-sensitivty parameters in 3 subjectsversus corresponding population nominal values
SubjectPopulation
I (477) II (486) III (476)
VH 0.65 1.37 2.13 1.17
βH 1.5 0.87 0.68 0.84
α 0.7 1.36 1.55 1.3
∆V 46 40 36 50
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 25 / 31
![Page 26: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/26.jpg)
Artificial Bionic Baroreflex
Figure: BP measurement (BP setpoint) vs. the results of the artificial bionic baroreflex(simulated BP) for individual with subject number: 477.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 26 / 31
![Page 27: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/27.jpg)
Artificial Bionic Baroreflex
Figure: The calculated control signal P0 in 3 subjects.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 27 / 31
![Page 28: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/28.jpg)
Summary and Conclusion
A mathematical model of the atutonomic-cardiorespiratory regulation+ oscillatory pattern origins
A parameter dientification technique to monitor sympathetic andparasympathetic nerve activities
A systematic approach to stability analysis ot autonomic-cardiacregulation
A method for the design of an artificial bionic baroreflex using asubject-specific mathematical model
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 28 / 31
![Page 29: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/29.jpg)
Future Work
To investigate the atutonomic-cardiorespiratory regulation using theproposed mathematical model
To validate the consistencey of the proposed parameter identificationresults with other markers of sympathetic and parasympatheticmarkers including HRV-based markers
To investige the occurence of positive feedback in theautonomic-cardiac regulation using the poposed systematic approach
To study the proposed method for the design an artificial bionicbaroreflex in the clinical experiments.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 29 / 31
![Page 30: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/30.jpg)
Publication
Journal Articles
P. Ataee, J.O. Hahn, Dumont, G.A., and W.T. Boyce. Non-Invasive Subject-SpecificMonitoring of Autonomic-Cardiac Regulation. IEEE Transactions on BiomedicalEngineering, submitted, 2012.
P. Ataee, J.O. Hahn, Dumont, G.A., Noubari H.A., and W.T. Boyce. A Model-BasedApproach to Stability Analysis of Autonomic-Cardiac Regulation. Journal of ComputerMethods and Programs in Biomedicine, submitted, 2012.
Refereed Conference Papers
P. Ataee, J.O. Hahn, C. Brouse, G.A. Dumont, and W.T. Boyce. Identification ofcardiovascular baroreflex for probing homeostatic stability. Computing in Cardiology,(37):141-144, 2010.
P. Ataee, J.O. Hahn, G.A. Dumont, and W.T. Boyce. A Systemic Approach to LocalStability Analysis of Cardiovascular Baroreflex. 33rd Annual International Conference ofthe IEEE EMBS, pages 700-703, 2011.
P. Ataee, L. Belingard, G.A. Dumont, H.A. Noubari, and W.T. Boyce.Autonomic/Cardiorespiratory Regulation: A Physiology-Based Mathematical Model. 34thAnnual International Conference of the IEEE EMBS, pages 3805-3808, 2012.
P. Ataee, G.A. Dumont, H.A. Noubari, W.T. Boyce, J.M. Ansermino. A Novel Approachto the Design of an Artificial Bionic Baroreflex. 35th Annual International Conference ofthe IEEE EMBS, accepted, 2013.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 30 / 31
![Page 31: Homeostasis Revisited in the Genesis of Stress Reactivity](https://reader034.vdocuments.us/reader034/viewer/2022042907/58e7d4121a28ab3a578b4b4f/html5/thumbnails/31.jpg)
Acknowledgement
Thank you.
Pedram Ataee (UBC) Ataee’s PhD Exam June 9, 2013 31 / 31