This document discusses using cardiopulmonary coupling measured through electrocardiogram (ECG) spectrograms to evaluate sleep quality and effectiveness. It notes current sleep evaluation focuses on electrocortical activity but ignores interactions between physiological systems like autonomic, respiratory, hemodynamic, and metabolic processes. ECG spectrograms allow mapping mathematical coupling between two signals like heart rate and respiration, providing a view of sleep as integrated physiological function rather than just brain states. Potential clinical applications discussed include screening for conditions affecting sleep, evaluating treatment efficacy, and detecting chemoreflex activation.

1. Sleep Quality Evaluation
with Cardiopulmonary
Coupling
ECG-spectrogram
Robert Joseph Thomas, M.D., M.M.Sc.
September 9 2013

2. Conflict of Interest Disclosures for Speakers
1. I do not have any potential conflicts of interest to disclose, OR
X 2. I wish to disclose the following potential conflicts of interest
Type of Potential Conflict Details of Potential Conflict
Grant/Research Support
Consultant
Speakers’ Bureaus
Financial support
Other
Intellectual property : ECG-spectrogram (Licensed, M1 device,
MyCardio, LLC) and positive airway pressure gas modulator
3. The material presented in this lecture has no relationship with any of these
potential conflicts, OR
x 4. This talk presents material that is related to one or more of these potential
conflicts, and the following objective references are provided as support for
this lecture:
1. Thomas RJ, Mietus JE, Peng CK, Goldberger AL. An electrocardiogram-based technique to assess
cardiopulmonary coupling during sleep. Sleep 2005;28:1151-61.
2: Thomas RJ, Daly RW, Weiss JW. Low-concentration carbon dioxide is an effective adjunct to positive airway
pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing. Sleep
2005;28:69-77.

3. Current state of affairs
 Electrocortical characterization of state in 30 second
epochs
 Supportive EOG, EMG
 Rest of brain and body ignored
 In reality – numerous physiological streams that are
relatively independent but interact, and are measureable
 Electrocortical - gene expression, proteomics, network effects
 Autonomic
 Hemodynamic
 Respiratory – airflow, neural drive, effective ventilation,
oxygenation
 Motor
 Metabolic – neuroendocrine

4. Single vs. coupled streams
 Individual physiological streams rich in biological
information
 EEG, ECG, respiration, oximetry, capnometry
 Common themes of biological activity show a
completely different picture of sleep – any
combination of 2 or more signals could be “coupled”
mathematically
 More based on analytic preferences
 Some coupling signals are intrinsically simpler
 Allows mapping of sleep, vs. scoring / counting
 Computes the “music” of sleep
 Plausible pairs include EEG + blood pressure, HRV +
respiration, motor activation + blood pressure, many others

5. Sleep effectiveness
 Sleep is able to perform its function
 Not stage specific
 Not likely graded, but smooth or bimodal
 Present all across the night
 Conserved across species
 Ineffective sleep
 Does not allow sleep function
 Concordant or discordant

6. Dimensions of sleep
effectiveness
 Electrocortical
 Autonomic
 Hemodynamic
 Motor
 Respiration – airflow, ventilation, oxygenation
 Metabolic – immune
 Gene expression
 Sleep-circadian interaction and integration

7. Peripheral Arterial Tonometry

8. Plethysmographic trace and PTT

9. Pulse Transit Time

10. Sleep Academic Award

11. CAP subtypes

12. CAP period

13. Non-CAP period

15. Sleep Academic Award

16. Sleep Academic Award

17. Cross-Spectral Power
Coherence
0
1
RR (f) EDR (f)
0 10 Hz0 10 Hz

18. Cross-Spectral Power
Coherence
0
1
RR (f) EDR (f)
0 10 Hz
Cardiopulmonary Coupling =
[Cross-Spectral Power]² X [Coherence]
0 10 Hz

19. Sleep spectrogram
8.5
2.1
512

20. Sleep spectrogram in health
High-
frequency
coupling
Low-
frequency
coupling

21. Slow wave power and ECG-
spectrogram

23. Integrated sleep effectiveness
 Non-CAP EEG
 Increased absolute (early night) and relative (any time of
night) slow wave power
 Continuous and dense NREM slow oscillation
 Blood pressure dipping
 Stable breathing (and oxygenation; ventilation may show
mild hypercapnia)
 Strong sinus arrhythmia
 High frequency cardiopulmonary coupling

24. Night-to-night stability

25. Sleep deprivation recovery
– increased HFC all across
the night
Rested -
human

26. Lorazepam
0.9 mg/Kg/
day

27. Development – CHIME data
“n”
1 = 53
2 = 151
3 = 121
4 = 62
5 = 34
6 = 22
Collaborative
Home
Infant
Monitoring
Evaluation

28. Development of sleep stability

29. Sleep fragmentation in Alzheimer’s
disease (transgenic mouse)

30. Sleep fragmentation in heart failure

31. Putting it all together…..

32. Putting it all together…..

34. Chemoreflex activated

35. Chemoreflex activated

36. Chemoreflex not activated

40. Limitations of ECG-spectrogram
 Atrial fibrillation or very frequent VPC’s
 Moving average, thus not sensitive to non-sustained
abnormality, such as brief clusters of central apneas
 Not specific to condition (but narrow band coupling likely
strong chemoreflex) – severe apnea could look like
severe pain or anxiety
 Clinical context is key

41. Plausible uses of the ECG-
spectrogram
 Screening for sleep quality
 Cancer
 Depression
 Epilepsy
 Combined with oximetry to screen for sleep apnea
 Insomnia treatment efficacy
 Modality agnostic
 PLMD/RLS treatment efficacy
 Efficacy of sleep apnea therapy
 Detection of strong and sustained respiratory
chemoreflex activation

46. Thank you
rthomas1@bidmc.harvard.edu