CSI is the integral of the difference between 2.50 (ORP in full wakefulness) and instantaneous ORP across the total recording time (Figure below). In practice, it is calculated from: [(2.50-ORPTRT) * TRT], where ORPTRT is the average ORP in all epochs, and total recording time (TRT) is in minutes (1). It differs from total sleep time as it includes sleep depth, and differs from sleep efficiency since dips in ORP during the microsleep periods that occur during stage Wake are included in the calculation. It is intended to provide a quantitative metric of the overall “wakefulness reduction” achieved during each study.
Figure: Hypnograms and epoch-by-epoch ORP from three subjects with normal conventional hypnograms. The horizontal dashed line is at ORP of 2.50, which represents full wakefulness. Cumulative Sleep Index (CSI) is the integral of the difference between 2.50 (full wakefulness) and instantaneous ORP (graph values) across total recording time, representing the total units of wake suppression during the study.
Note: The marked difference in the ORP time course and how this is reflected in their CSI values. (Reference 2).
The main utility of CSI is that it provides the “amount” of sleep (time*depth) achieved by the patient during a sleep study. When this value is related to the value needed by the patient to achieve the full restorative function of sleep (CSI needed), it can provide valuable information on the mechanism of excessive daytime somnolence. CSI needed in the individual patient with excessive sleepiness can be obtained by asking the patient to have unrestricted sleep with spontaneous awakening in the morning for several days (e.g., while on holiday) until EDS improves, at which point the sleep study is repeated. CSI measured then may be considered the “needed CSI”. Relating the CSI measured during the patient’s regular sleep to the needed value will indicate the extent of sleep insufficiency that needs to be corrected through improving sleep depth or increasing sleep time (see figure below).
Values of CSI in “confirmed” normal sleepers are not available, and such studies require the participating subjects to be free of sleep disorders, be free of EDS on a regular nocturnal sleep of <9 hours, and not on sleeping meds or stimulants. As an alternative, we determined CSI in selected participants of the Sleep Heart Health Study (SHHS) who were likely to be normal sleepers based on the information provided in the National Sleep Research Resource (NSRR, https://sleepdata.org/). Panel A (Figure below) shows CSI vs. age in 1516 participants with no OSA or insomnia and with TRT > 7 hours, to exclude short studies due to technical issues. In this group, the average CSI at age 40 was 737, and the average decreased by 4 units per year. There was a wide range (±2 SD) at any age (±190 units), showing that sleep need, as defined by CSI, is highly variable among individuals.
Of the above group, participants with total sleep time > 7 hours were excluded in the event they were sleep deprived during the single sleep study or had idiopathic hypersomnia. The selection was further narrowed by excluding those who slept more on weekends than during the week (suggesting insufficient sleep during the week), using sleeping pills regularly or benzodiazepines or antidepressants within two weeks of the sleep study, or experiencing excessive somnolence more than 4 times per month, leaving 620 participants. These were presumed to be normal sleepers. Panel B shows the relation between CSI and age in these “Normal” sleepers. The relation between average CSI and age was essentially the same as in panel A, but the range at any age (±2 SD) narrowed but remained large (± 150 units). These observations suggest that the amount of needed sleep (duration * sleep depth) is individual-specific and age-dependent.
The above findings suggest an approach for identifying the mechanism of symptoms of insufficient sleep (EDS), non-restorative sleep, and for identifying “short sleepers”. Using the equation of CSI (CSI= (2.50 - ORPTRT)*TRT), the TRT required to reach any specified CSI at any specified ORPTRT can be calculated. The isopleths in panels C and D describe the time required to achieve specified CSI values in 5, 7, 9, 11, 13, and 15 hours. Thus, at an average ORPTRT of 1.0, a subject needs 5 hours of bedtime to accumulate 470 CSI units, 7 hours of bedtime to accumulate 640 units, and 15 hours of bedtime to accumulate 1350 units.
Panel C shows the results of all SHHS participants with no OSA or insomnia, including those whose TRT time was < 7 hours (n= 2454) when plotted against the background of the isopleths. This figure illustrates the wide range of ORPTRT (0.50-2.00) and the wide range of CSI (200-1000) in community dwellers. In most participants, the relation between the two variables was such that the needed sleep was accommodated in between 7 and 9 hours.
However, TRT was < 7 hours in 940 participants (38%). The trapezoid in panel C encloses potential short sleepers (CSI >350, similar to the lowest CSI in normal sleepers, panel D), if it can be confirmed that the CSI achieved is the needed CSI.
Of these, we excluded those with any indication of EDS (see above re: normal sleepers), leaving 463 within the trapezoid. In this group, TRT ranged 293 to 418 minutes (376±39) with 30 having TRT less than 5 hours, CSI ranged 404 to 701 (545±88), well within the range in normal sleepers (Panel D), and their sleep depth (ORPTRT) ranged 0.69 to 1.40 (1.04±0.21), which is lower than the range of the normal sleepers (0.77 to 1.58; (1.15±0.25).
These findings suggest that short sleepers (needed TRT < 7 hours) are fairly common.
Figure:
A) CSI in 1516 participants of the SHHS who were free of OSA and insomnia and who slept 7 to 9 hours, arranged by age.
B) Same participants after excluding those with any indication of insufficient sleep.
C) Relation between ORPTOT and CSI in 2464 participants of the SHHS who were free of OSA or insomnia. Isopleths represent the number of hours of sleep needed to reach different CSI. Note that in most participants, the needed hours fell between 7 and 9 hours. However, many slept for < 7 hours. The orange trapezoid encloses those with CSI > 350, which is within the range encountered in normal sleepers. After excluding those with any indication of insufficient sleep from this group, 463 remained with CSI within the normal range, sleeping < 7 hours, and with no indication of insufficient sleep.
D) Same relation but excluding those with < 7 hours of sleep and those with any indication of insufficient sleep. Red square, average result from 16 bona fide short sleepers (see text). Red Stars: 4 examples of subjects with very long sleep duration having different levels of ORPTOT and CSI (within the range reported by Thomas et al (3)). Arrows represent the amount of improvement in ORPTOT so that the needed CSI can be achieved within 9 hours.
A recent study on 16 well-documented habitual short sleepers (TRT < 6.5 hours) who were healthy, non-obese young adults with no sleep complaints (PSQI=5.1±2.4) found that their ORPTRT was 0.79±0.23 (red square, panel D) (4). This supports the use of the relation between ORPTRT and CSI (low ORPTRT at normal or high CSI) to identify habitual short sleep duration. Short sleep duration is associated with several poor health outcomes, including mortality, diabetes, and cardiovascular disease (5,6). It is not clear whether this type of short sleep duration (i.e., associated with deep sleep) is protected from these poor outcomes. The study by Stegman et al (4) found that their participants had increased insulin resistance, a precursor to diabetes, despite normal CSI and better-than-average sleep depth. This suggests that the deeper sleep seen in such short sleepers is not protective against diabetes. Much work is needed to determine the susceptibility of habitual, asymptomatic, short sleepers to the various poor outcomes reported in short sleepers.
In another study, 36 patients with documented long sleep need (>10 hours) underwent unrestricted polysomnography. Total sleep time by visual scoring (TST) was 679 ± 96 minutes (range: 601 - 1145 minutes), confirming the excessive sleep need in all. Whole night CSI ranged from a very low 345 (cf. panel D) to a high of 1427, and there was no correlation with TST or TRT (3).
A substantial minority of patients (≈40%) had CSI values within the range seen in normal sleepers (300-900 units, panel D) (3), indicating that these patients do not have excessive sleep need. Patients representing this normal CSI range are represented by the lower stars in panel D.
In these patients, the problem is that their average sleep depth (ORPTOT) was such that their needed CSI could not be achieved within the typical 7-9 hours of nocturnal sleep. In the remaining patients, CSI was well above the range that could be achieved even with the lowest possible ORPTOT in 9 hours (upper two stars in panel D). The red arrows in panel D indicate the reduction in needed sleep time if sleep depth can be improved and show that in the lower two patients, a small improvement in ORPTOT, produced through physiological or pharmacological means, may restore needed sleep time to a normal level, while in those with excessive needed CSI, only some reduction in sleep time can be achieved (upper two stars).
In this respect, it should be noted that while many available sleep aids do improve sleep efficiency and reduce arousals, their reported effects on EEG’s spectral density are not consistent with lowering of ORP, which occurs when power in slow EEG frequencies increases and power in the higher frequencies decreases. Whether sedatives that do not lower ORP can benefit patients with idiopathic hypersomnia remains to be determined.
These two studies, along with the interpretation framework shown in the figure, suggest that the control of sleep depth (ORPTOT) and the control of sleep need (CSI) are not strongly linked. Sufficient sleep in 7-9 hours is only achieved when the two variables are appropriately matched; when ORPTOT is low relative to needed CSI, the subject becomes a habitual short sleeper. And when the opposite occurs, the subject becomes a habitual long sleeper or suffers from excessive somnolence. The framework of the figure may also help select patients who might be normalized with available therapies.
Finally, EDS need not be present only in subjects who need > 9 hours of sleep. Using the same logic, a subject who habitually sleeps a normal 7 or 8 hours may be chronically sleep deprived if attaining their needed CSI requires 9 hours at their ORPTOT. For this reason, patients who are sleepy at what appears to be enough, high-quality (low ORPTOT) sleep may benefit from extending sleep time or from measures to improve ORPTOT (increasing SE and/or appropriate sedatives).
Relevant References: