An Online Metric Of Sleep/Wake Using the Unitary Measure, Z-ratio.

1. ZOMNOGRAPHY An Online Metric Of Sleep/Wake Using the Unitary Measure, Z-ratio. Claude Albertario, RPSGTMineola, NY USA

2. Polysomnography EEG Patterns ? ? Adapted From: Current Concepts: The Sleep Disorders. Peter Hauri, The Upjohn Company, 1977 WINTHROP UNIVERSITY HOSPITAL

3. “Call to Arms” From: Dement, William C., Commentary, Sleep: An Active Process, Ed.Wilse Webb, Scott, Foresman & Co. 1973, pg. 49. WINTHROP UNIVERSITY HOSPITAL

4. “Call to Arms” cont’d • “More studies are needed that evaluate "sub-cortical" arousals, EEG arousals, and daytime function simultaneously.” As stated in:The effect of sleep fragmentation on daytime function, Stepanski EJ. Sleep. 1984;7(1):18-26 WINTHROP UNIVERSITY HOSPITAL

5. Polysomnography EEG Patterns BETA>12 cps ALPHA8-12 cps MIXED { THETA3-7 cps Adapted From: Current Concepts: The Sleep Disorders. Peter Hauri, The Upjohn Company, 1977 DELTA.5 –2 cps WINTHROP UNIVERSITY HOSPITAL

6. Standard R&K Scoring • “Stage 1 is defined by a relatively low voltage, mixed frequency EEG with a prominence of activity in the 2-7 cps range.” • “The faster frequencies are mostly of lower voltage than the 2-7 cps activity.” Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects., Rechtschaffen A, Kales A, eds., Los Angeles: UCLA Brain Information Services/Brain Research Institute; 1968. WINTHROP UNIVERSITY HOSPITAL

7. Standard R&K Scoring cont'd • The information used to determine sleep or wake is derived specifically from the EEG. • The EOG and EMG are used basically to “qualify” sleep stage, NOT determine sleep vs. wake per se. WINTHROP UNIVERSITY HOSPITAL

8. Lower Faster Frequency Voltage Slower Higher SLEEP/WAKE EEG Pattern Recognition Adapted From: Current Concepts: The Sleep Disorders. Peter Hauri, The Upjohn Company, 1977 WINTHROP UNIVERSITY HOSPITAL

9. Historical EEG “Relativity” Analyses • Inter-hemispheric EEG studies reflect the RMS power between hemispheres using a simple relational formula: Left Power – Right Power Left Power + Right Power(“Total Power”) WINTHROP UNIVERSITY HOSPITAL

10. A new Tool: The FFT • “Fast Fourier Transform: A class of algorithms used in digital signal processing that break down complex signals into elementary components.” http://computing-dictionary.thefreedictionary.com/FFT WINTHROP UNIVERSITY HOSPITAL

11. FFT Results of a simple 5 Hz signal WINTHROP UNIVERSITY HOSPITAL

12. FFT Results of a simple 10 Hz Signal WINTHROP UNIVERSITY HOSPITAL

13. FFT Results of a mixed 5Hz+10Hz Signal WINTHROP UNIVERSITY HOSPITAL

14. FFT Results of a Multi Hz signal WINTHROP UNIVERSITY HOSPITAL

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16. } FAST>7 cps“WAKE” SLOW<7 cps“SLEEP” BETA>12 cps ALPHA8-12 cps MIXED { THETA3-7 cps Adapted From: Current Concepts: The Sleep Disorders. Peter Hauri, The Upjohn Company, 1977 DELTA.5 –2 cps WINTHROP UNIVERSITY HOSPITAL

17. R&K derived 1 sec Z-ratio “Domains” • Frequencies SLOWER than 7 cps are considered SLEEP related in nature SLOW = SLEEP • Frequencies FASTER than 7 cps are considered WAKE related in nature FAST = WAKE WINTHROP UNIVERSITY HOSPITAL

18. “prominence” • prominence: noun: relative importance • Z-Ratio depicts the prominence of the background EEG, as instructed in R&K, by numerically highlighting the relative contribution of the slow frequencies compared to the wake frequencies. WINTHROP UNIVERSITY HOSPITAL

19. R&K Meets FFT • Z-Ratio depicts the relative contribution of frequency domains derived from the Fast Fourier Transform. “SLEEP” (<7cps) – “WAKE” (>7cps) “SLEEP” (<7cps) + “WAKE” (>7cps) (“TOTAL POWER”) WINTHROP UNIVERSITY HOSPITAL

20. Z-ratio Examples When the background EEG has more power in the FASTER frequencies (>7 cps) the Z-ratio will be NEGATIVE (SLOW – FAST)(SLOW + FAST) (0-1) 1 = = -1 WINTHROP UNIVERSITY HOSPITAL

21. Z-ratio Examples cont’d When the background EEG has more power in the SLOWER frequencies (<7 cps) the Z-ratio will be POSITIVE (SLOW – FAST)(SLOW + FAST) (1-0) 1 = = +1 WINTHROP UNIVERSITY HOSPITAL

22. Review of Z-ratio publications • Quantification of Sleep/Wake in 2 seconds of EEG, Albertario, C. and Maberino, M., Journal of Polysomnographic Technologists, Dec. 1991 • First described the algorithm and depicted the onset of sleep using 2 second epochs of Z-ratio. WINTHROP UNIVERSITY HOSPITAL

23. Review of Z-ratio publications cont’d • Computerized Quantification of Sleep and Wakefulness in the EEG, Albertario, C., Hertz, G. and Feinsilver, S., Sleep Research, 1991. • Across 10 normal subjects: • The Mean Z-Ratio for each stage was significantly different from every other stage at the p<.01 level or better, except for REM and Stage 2 which were not significantly different. • “No patient demonstrated a mean Z-ratio that was negative during sleep.” WINTHROP UNIVERSITY HOSPITAL

24. Review of Z-ratio publications cont’d • Comparisons of Z Ratio and Standard scoring techniques for sleep/wake determination on the MSLT, Albertario, Zendell, Hertz, Maberino, and Feinsilver, Sleep Research, 1992 • By using a Z-page threshold between -.10 and -.15 , Central and Occipital Z-Ratio agreement with expert scorers was 89% and 93% respectively. WINTHROP UNIVERSITY HOSPITAL

25. Review of Z-ratio publications cont’d • Comparison of a Frequency-based Analysis of Electroencephalograms (Z-Ratio) and Visual Scoring on the Multiple Sleep Latency Test, Albertario, et al. Sleep, 1995 • 80% kappa for Sleep/Wake determination comparing Z-ratio to expert scorers. WINTHROP UNIVERSITY HOSPITAL

26. Review of Z-ratio publications cont’d • Visual Scoring Versus Quantitative EEG Analysis: An Ambulatory Home PSG Study, Von Gizycki et al., Sleep Vol. 22 Supplement #1, 1999 • Found no significant differences between Z-ratio and visually scored methods of sleep/wake • Agreement as to sleep or wake, was 87% between expert scorers and Z-ratio “Together, these observations suggest that the Z-ratio method could be used to perform quantitative analysis of EEG data during day and night.” WINTHROP UNIVERSITY HOSPITAL

27. Applying Z-ratio on Previous data • Discrimination Among States of Consciousness Using EEG Spectra, Lubin, A, Johnson, LC, Austin, MT, Psychophysiology, 1969, 6, 122-132 as reprinted in Sleep: An Active Process, Wilse Webb, Scott, Foresman & Co. 1973, pg. 103 “Spectral Analysis of the parietal EEG lead does not provide enough information to differentiate among stages W, 1, 2, 3, 4 and REM” WINTHROP UNIVERSITY HOSPITAL

28. Negative Z-ratio Positive WINTHROP UNIVERSITY HOSPITAL

29. Used as an “Online” tool • … can be performed on each EEG channel independently, no ancillary parameters required • … is UNITARY in that the algorithm can be computed from ANY EEG analysis, as long as the source EEG analysis does not perform a priori frequency weighting • … does not “score sleep,” instead It provides a metric upon which to gauge sleep/wake • …is the only simple, transparent, intuitive reduction of EEG into a single per second quantified sleep/wake metric WINTHROP UNIVERSITY HOSPITAL

30. Present On-line Z-ratio from Medcare WINTHROP UNIVERSITY HOSPITAL

31. Z-ratio in Analysis WINTHROP UNIVERSITY HOSPITAL

32. Z-ratio Depicting Spindles (confound?) WINTHROP UNIVERSITY HOSPITAL

33. Possible analyses using Z-ratio • Viewing second by second EEG based numeric FFT values allows for new methods and constructs of depicting human sleep. WINTHROP UNIVERSITY HOSPITAL

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39. Percentiles plot of 1 sec Z-ratios WINTHROP UNIVERSITY HOSPITAL

40. Frequency Distribution WINTHROP UNIVERSITY HOSPITAL

41. Some Further analyses using Z-ratio • Multi-site Z-ratio mapping • Infradian, Circadian and Ultradian EEG rhythmicity similar to limb movements recorded by actigraphy over multiple 24hr periods blindly to subjective mental state and etiology. WINTHROP UNIVERSITY HOSPITAL

42. External EDF file WINTHROP UNIVERSITY HOSPITAL

43. Posing Questions • Is the following activity Cyclic Alternating Pattern, or Chervin’s “Respiratory cycle-related EEG changes (RCREC)“? • Method for detection of respiratory cycle-related EEG changes in sleep-disordered breathingChervin RD, Burns JW, Subotic NS, Roussi C, Thelen B, Ruzicka DLSleep. 2004 Feb 1;27(1):110-5 WINTHROP UNIVERSITY HOSPITAL

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45. During SWS WINTHROP UNIVERSITY HOSPITAL

46. Through Apneas WINTHROP UNIVERSITY HOSPITAL

47. Also through REM WINTHROP UNIVERSITY HOSPITAL

48. Rhythms, Respiration and EEG • Is it respiration influencing EEG or an underlying EEG rhythmicity influencing or controlling respiration and/or other bodily functions? • The influence of the respiratory cycle on the EEGBusek P, Kemlink D.Physiol Res. 2005;54(3):327-33 • Electroencephalographic Changes during Respiratory Cycles Predict Sleepiness in Sleep Apnea, Chervin et al. Am. J. Respir. Crit. Care Med..2005; 171: 652-658 • The cyclic alternating pattern as a physiologic component of normal NREM sleep.Terzano MG, Mancia D, Salati MR, Costani G, Decembrino A, Parrino L.,SLEEP 1985;8:137-45 • Obstructive sleep-disordered breathing with a dominant cyclic alternating pattern—a recognizable polysomnographic variant with practical clinical implications.Thomas RJ; Terzano MG; Parrino L; Weiss JW., SLEEP 2004;27(2):229-34. WINTHROP UNIVERSITY HOSPITAL

49. Further analyses using Z-ratio cont’d • Novel and transparent methods of depicting: • Arousal Time • Micro-Sleep during wake time • Cyclic Alternating Pattern? • Circadian sleep/wake EEG information • Epileptiform activity • Highlighting normal sleep EEG phenomenon • Tracé-Alternant • Spindling, K-complexes • Vertex sharp waves • Delta and Alpha bursts WINTHROP UNIVERSITY HOSPITAL

50. Pros of utilizing Z-ratio • Does not stage sleep • Can be performed on-line • Single intuitive value • Impervious to sensitivity/gain and voltage changes • Can be used across hardware platforms and/or analysis routines • Can be performed identically, repeatedly • Needs no calibration procedure WINTHROP UNIVERSITY HOSPITAL