Humidity and sleep: A review on thermal aspect

Abstract

The peripheral humidity detector/detection is not clear though there are
comprehensive reports of subjective perception. High relative humidity at
ambient temperatures above thermo-neutral zone has deleterious effect on sleep.
Humidity affects heat transfer rate by affecting evaporation and thereby
disturbing the Tc and Ts dynamics. The effect is discernible across a host of
sleep, body temperature, and microclimate indices. A number of hypotheses have
been proposed to explain the sleep structure regulation of which circadian–
homeostatic interaction model is the most accepted one. Humid heat may affect
sleep through homeostatic pathway possibly interfering with adenosine accumulation
in basal forebrain and thereby affecting non-rapid eye movement (NREM)
sleep switch point. It may also have a circadian element by interfering with
thermo-regulatory feedback loop and/or by affecting Ts change input to sleep
regulation.

Full text

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Running head
Md. D Manzar, M Sethi, ME Hussain. Biological Rhythm Research
Article type
Review
Title
Humidity and sleep: A review on thermal aspect
Authors
Md. Dilshad Manzar
a1
[Md. D. Manzar], Mani Sethi
a2
[M. Sethi], M.Ejaz Hussain*
a
[M.
E. Hussain]
Affiliation
a
Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi,
India
Postal address
Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, Maulana
Mohammad Ali Jauhar Marg, New Delhi-110025, India
Telephone Number
+91-11-26981717 ext. 4523,
Email Addresses
1
md.dilshadmanzar@gmail.com,
2
manisethi83@gmail.com
*Correspondence author details
Email: ejaz58@yahoo.com, telephone: +91-11-26980544

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Abstract
The peripheral humidity detector/detection is not clear though there are comprehensive
reports of subjective perception. High relative humidity at ambient temperatures above
thermo-neutral zone has deleterious effect on sleep. Humidity affects heat transfer rate by
affecting evaporation and thereby disturbing the Tc and Ts dynamics. The effect is
discernible across a host of sleep, body temperature and microclimate indices. A number
of hypotheses have been proposed to explain the sleep structure regulation of which
circadian-homeostatic interaction model is the most accepted one. Humid heat may affect
sleep through homeostatic pathway possibly interfering with adenosine accumulation in
basal forebrain and thereby affecting NREM sleep switch point. It may also have a
circadian element by interfering with thermo-regulatory feedback loop and/or by
affecting Ts change input to sleep regulation.
Keywords: sleep; humidity; temperature; circadian and homeostatic

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1. Introduction
Humidity is one of the six important variables defining human thermal comfort and hence
sleep (Fanger 1970; Shapiro and Epstein 1984; IUPS Thermal physiological commission
2001). It becomes critical at high ambient temperature and humidity because evaporation
(the most pronounced heat loss mechanism in the condition) is compromised (Havenith
1999). However, the peripheral detection and neurophysiology of humidity effect is still
not characterized (Clark and Edholm 1985; Nielsen and Endrucisk 1990; Li 2005). The
review was summarized to systematize the thermal and neuro-physiological elements in
the available literature. This may help to give specific direction to the future research as
regards:
i. mechanistic characterization of sleep and humidity interaction
ii. development of sleep management strategies through feasible modulation of
human thermal comfort factors
High humid heat condition has deleterious effect on sleep parameters with
increasing effect on stage Wake, WASO (wake after sleep onset), sleep latency, stage 1
and decreasing effect on SWS (slow wave sleep), stage 3, REM, TST (total sleep time)
and SEI; sleep efficiency index (Okamoto-Mizuno et al. 1999, 2003; Okamoto-Mizuno,
Tsuzuki, Mizuno, Iwaki 2005; Okamoto-Mizuno, Tsuzuki, Mizuno 2005; Buguet 2007;
Tsuzuki et al. 2008; Okamoto-Mizuno and Tsuzuki 2010). Similarly, thermo-
physiological effect of humidity on sleep has been reported in terms of a number of body
temperature indices (Okamoto-Mizuno et al. 1999, 2003; Okamoto-Mizuno, Tsuzuki,
Mizuno, Iwaki 2005; Okamoto-Mizuno, Tsuzuki, Mizuno 2005; Buguet 2007; Tsuzuki et
al. 2008; Okamoto-Mizuno and Tsuzuki 2010). A number of hypotheses have been
proposed to explain the sleep structure regulation of which four have been discussed. The
homeostatic-circadian interaction model initially proposed by Borbely is the most
accepted on sleep structure regulation (Borbely 1980, 1982; Daan et al. 1984; Czeisler
and Khalsa 2000; Wurtz and Edgar 2000). Later, Palchykova et al. (2003), Rattenborg et
al. (2004), Saper et al. (2005, 2010) suggested an allostatic dimension in sleep structure
regulation.
There are missing links in the neuro-physiological and thermo-physiological
explanations of sleep structure regulation in general as well as in context of humid heat,
therefore they warrant further research. One explanation may be that humid heat because
of its more pronounced effect on homeostatic sleep parameters appears to effect sleep
through homeostatic pathway possibly interfering with adenosine accumulation in the
basal forebrain and thereby affecting NREM sleep switch point (Radulovacki et al. 1984;
Benington and Heller 1995; Strecker et al. 2000; Scammell et al. 2001; Porkka-

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Heiskanen et al. 2002; Aloe et al. 2005; Saper et al. 2001, 2005, 2010). However, this
may have a circadian element as well with humid heat disturbing the circadian
thermoregulatory feedback loop to the central nervous system (Van Someren 2000).
More recently, subtle Ts (Ts means skin temperature of peripheral body part/parts)
change has been suggested and shown to work as an independent input to the sleep
structure regulating centres with circadian and behavioural characteristics (Van Someren
2003, 2004, 2006; Raymann et al. 2005, 2008; Fronczek et al. 2006, 2008; Raymann and
Van Someren 2008). Humidity may have an effect on sleep by altering rate of Ts change
by affecting the moisture content at skin/environment interface and therefore the specific
coefficients of heat transfer.
2. Subjective perception of humidity
The human thermal sensation and comfort is defined by the interactions of six
fundamental factors. Ambient temperature, radiant temperature, humidity and air
movement are the four basic environmental variables; the metabolic rate and clothing
(insulation and moisture permeability characteristics) are the behavioral variables
affecting human response to thermal environment (Fanger 1970; Shapiro and Epstein
1984; IUPS Thermal physiological commission 2001). The body temperature equilibrium
requires a constant exchange of heat between the body and the environment which is
essential for maintaining Tc (37±1º C) and normal body physiology. Tc stands for core
body temperature and it can be measured from rectal and gut temperatures. Therefore, for
simplification of the fact presentation core body temperature reported from measurement
sources, gut or rectum will be addressed simply as Tc (Waterhouse et al. 2005). The
basic heat balance equation is:
∆S= (M-Wex) ± (R+C+K+L) -E ..................(1) (Havenith 1999; Kwok 2001)
Where: ∆S = change in body heat content; (M-Wex) =net metabolic heat production
from total metabolic heat production (Wex=mechanical work); (R+C+K+L) = radiative,
convective, conductive and heat exchange in breathing respectively; E=evaporative heat
loss. The mathematical expressions defining the rules governing their systematic are as
under:
K=f[Sh(Tm-T)] …………………..(2)
C=cS(Tm-T)………………………(3)
R=as(dTo4-eT4)…………………...(4)
E=f[S(hrPa-P)]……………………(5)
Where, ‘f’, ’h’ (eqn-2), ‘c’ (eqn-3), ‘a’, ‘s’, ‘d’ (eqn-4) and ‘f ‘(eqn-5) represent different
heat transfer constants. ‘S’ represent the body surface area/ exposed body surface area,

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‘Tm’ and ‘To’ is more representative of ambient temperature whereas T of the skin
temperature respectively.
The contribution of M, Wex and L to ∆S during sleep is not of prime importance
because of negligible contribution to intersystem/inter-individual differences. The most
pronounced effect is of K, C, R and E. At high ambient temperature K, C and R have
positive values and lead to body heat gain. Therefore the bulk of heat loss at high ambient
temperature is assigned to evaporative mechanism, however high ambient temperature at
high relative humidity (RH) disrupts even this evaporative heat loss (Havenith 1999).
(This is a simple presentation of the thermodynamics, interested reader is referred to
Havenith 1999, Kwok 2001 for detailed account). Under normal circumstances, Tc
decreases and Ts increases resulting in a characteristic distal proximal gradient (DPG)
creation between Tc and Ts, which leads to increase in heat loss at sleep/NREM sleep
onset (Van Someren 2000). However, this heat loss is disrupted at high humid heat
condition, because evaporation (the most prominent heat losing mechanism at high
ambient temperature) is negatively affected.
Nielsen and Endrusick (1990) observed that the sensation of humidity is co-
related with skin wetness. Li (2005) reported that the psychological perception of
dampness (clothing) is positively and non-linearly correlated with the relative humidity
(clothing microclimate humidity) at the skin surface. However, the neuro-physiological
mechanistic characterization of neither moisture nor humidity perception is clear,
therefore no general consensus of opinion about specific moisture detector in human
beings (Clark and Edholm 1985). Kenins and Spence (1992 cited Li 2005) reported that
there is little evidence to support the assumption of a specific humidity detector in
humans and opined that humidity might be perceived through some indirect mechanisms.
Moreover, a rigid extension of the receptor specificity theory to every mechanism
involved in stimulus/sensation detection conflicts with the complexity and multimodal
characteristics of many peripheral receptor responses to thermal, mechanical and
chemical stimuli (Belmonte and Viana 2008; Green and Akirav 2010; Wicher 2010).
Goldscheider & Hahn (1925 cited Hensel and Zotterman 1951), working with various
solutions, came to the conclusion that the mechanoreceptors actually respond to cooling
(in a smaller degree perhaps also to heating), though they couldn’t stimulate the receptors
of the largest pressure fibres by cooling (Hensel and Zotterman 1951; Green and Pope
2003; Green and Schoen 2005; Green and Akirav 2007). This cannot be explained as
arising due to secondary mechanical stimulation of the pressure receptors by local
vasoconstriction or to stimulation of the nerve trunk by cooling. Additionally,
heating/cooling the skin of the forearm and hand to mild temperatures (e.g., 28°C, 36°C)
causes some individuals to experience nociceptive sensations such as burning and
stinging (low threshold thermal nociception) with hot and cold condition (Green and
Pope 2003; Green and Schoen 2005; Green and Akirav 2007; Green et al. 2008; Green

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2009). The strongly evident humidity perception and the concomitant absence of specific
peripheral detectors necessitates evolution of hypothesis/model which explains the
subjective perception and give direction to research initiatives to discovery of its neuro-
physiological basis.
3. Humidity and sleep indices
Humid heat affects sleep and the effect has been reported in terms of a number of sleep
indices with all the studies (summarised in Table 1) having reported increase in stage
Wake/ wakefulness, whereas some have described in terms of increased longest wake
episode (Okamoto-Mizuno and Tsuzuki 2010), sleep interruptions (Buguet 2007) and
WASO (Okamoto-Mizuno et al. 2004; Tsuzuki et al. 2008). Stage 1 had also been
demonstrated to be increased by four groups (Tsuzuki et al. 2004; Okamoto-Mizuno,
Tsuzuki, Mizuno, Iwaki 2005; Buguet 2007; Tsuzuki et al. 2008). The majority of the
studies show decrease in SWS and/or Stage 3 and/or stage 4 (Okamoto-Mizuno et al.
1999, 2003; Okamoto-Mizuno, Tsuzuki, Mizuno, Iwaki 2005; Tsuzuki et al. 2004, 2008;
Buguet 2007). Similarly, humid heat has also been shown to decrease SEI (Okamoto-
Mizuno et al. 1999, 2004; Tsuzuki et al. 2004; Okamoto-Mizuno and Tsuzuki 2010), and
REM (Okamoto-Mizuno et al. 1999, 2003, 2004). Table 1 describes the summary of the
work by these groups in terms of subject (age, gender), study design, measurements
reported, intervention (type, temperature, RH) and outcome (sleep and body temperature
indices).
Okamoto-Mizuno et al. (1999) showed almost a regular gradation in effect on
sleep parameters with increase in temperature and humidity (Figure 1). Stage wake
increased and stage 3, SWS, REM and SEI decreased with increase in temperature and
humidity, though these effects were significant only at 35/75 ( numerical values
expressed on both sides of a slash here on implies X/Y; X º C and Y % RH) which shows
inefficient sleep under this condition. The study reported bulk of significant differences
in percentages of sleep indices in the 1st NREM/REM sleep cycle under different
conditions of temperature and humidity. Okamoto-Mizuno and Tsuzuki (2010) based on
actigraphic study demonstrated that wakefulness, longest wake episode and sleep
latency increases and total sleep time and sleep efficiency index decreases with seasonal
increase in bedroom temperature and relative humidity. Buguet (2007) studying sleep
under natural hot-humid and dry condition in African volunteers reported numerous sleep
interruptions and wakefulness amounting to 15.8% of sleep period time in hot-humid
condition. However, the results were not clearly discernible as stage 1 and REM was
comparatively more and SWS less under dry condition. This may have been because of
the lesser degree of control on other environmental factors, which may have confounded
the results.

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Okamoto-Mizuno, Tsuzuki, Mizuno, Iwaki (2005) working with partial humid
heat exposure during first 3.45 hour and second 3.45 hour of sleep duration elucidated the
circadian aspect of humidity mediated effect on sleep indices. Increase in stage Wake and
stage 1 while decrease in SWS is more pronounced with 1st half humid heat exposure
than in later half. Okamoto-Mizuno, Tsuzuki, Mizuno (2005) showed that sleep
disruptive effect is almost proportionate to duration of exposure (humid heat) though
there is comparatively lesser sleep disruption with humid heat exposure in later half of
sleep. Increased wakefulness in the 2nd segment was not related to a decrease in REM
suggesting that humid heat exposure may affect SWS more than REM. A degree of
caution is recommended in proportionate effect translation because future studies with a
graded temporal exposure of humid heat are warranted which may bring still clearer
picture. Tsuzuki et al. (2008) reported that stage Wake, stage 1, movement time (MT) and
wakefulness after sleep onset increased whereas stage 2, stage 4, TST decreased
significantly with humid heat. Airflow (1.7 m s−1) reduced wakefulness and increased
TST, stage 4 and SWS during sleep in a warm humid climate and helped manage sleep in
a warm humid climate. This may have been because of heat loss facilitation by
convective process. Okamoto-Mizuno et al. (2003) demonstrated that humans under
32/80 show marked difference in sleep characteristics in comparison to subjects at 25/50.
The frequency and total duration of stage Wake increased while REM and SWS
decreased under 32/80. The authors report a slight improvement in sleep with the usage
of head cooling; however the effect is not evident in respect of significant difference in
sleep indices rather is indirect extrapolation of observed decrease in the whole-body
sweat rate (whole body-sweat rate =whole body sweat loss or body mass loss divided by
time = Wbefore sleep-Wafter sleep / TST) during sleep under humid heat conditions.
Tsuzuki et al. (2004) reported significant increase in stage Wake, stage 1 and MT with
concomitant decrease in stage 2, stage 4 and SEI at 32/80 in comparison to 25/50.
Okamoto-Mizuno et al. (2004) working on healthy elderly population described a
significant increase in wakefulness and WASO while there was significant decrease in
REM and SEI at 32/50 as against 25/50. The results are in unison with results of other
studies but do point to the future research directions for optimization of humidity range at
different temperatures, this may have important inference for sleep management
strategies in respect to humid heat. Only one of the studies attempted to decipher humid
heat effect on sleep in perspective of rhythm markers (Tsuzuki et al. 2004), therefore its
imperative to look into the effects (humid heat) in terms of rhythm markers like
melatonin, leptin, cortisol and catecholamine (Manzar and Hussain 2010), this may help
give still more clear picture about the effect constitution as regards homeostatic and
circadian elements.
4. Humidity and body temperature indices
Humidity affects body temperature indices during sleep and the effect has been reported
in terms of a number of body temperature indices (Okamoto-Mizuno et al. 1999, 2003;

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Okamoto-Mizuno, Tsuzuki, Mizuno, Iwaki 2005; Okamoto-Mizuno, Tsuzuki, Mizuno
2005; Tsuzuki et al. 2004; Tsuzuki et al. 2008; Okamoto-Mizuno and Tsuzuki 2010). The
Tsk increased/decreased significantly within 15 min after ambient temperature and
humidity change, while increase/decrease in Tc was delayed by 30 min during sleep
(Okamoto-Mizuno, Tsuzuki, Mizuno, Iwaki 2005; Okamoto-Mizuno, Tsuzuki, Mizuno
2005). Tsk represents mean weighted skin temperature calculated by either Ramanathan
or Hardy and DuBois method (Tsk
1
/Tsk
2
in table) in the text for simplification of
presentation (Hardy and DuBois 1938, Ramanathan 1964), however the difference has
been mentioned in the footnote of Table 1.The effects are in parallel with those for wake
human subjects (Krauchi and Wirz-Justice 1994; Iwase et al. 2002), the time lag between
Tc and Ts change depends on the degree of thermal insulation, Tc change is subject to
longer time lags relative to Ts (Gilbert et al. 2000). Humid heat in first half of sleep is
associated with delayed Tc decline, and cooling effects while there is no such effect for
similar humid heat exposure in a later segment of sleep implying humid heat exposure in
the initial segment of sleep may affect thermoregulation more so than if occurring during
later segment of sleep. The clothing microclimate humidity and clothing microclimate
temperature increased with humid heat exposure (Okamoto-Mizuno, Tsuzuki, Mizuno,
Iwaki 2005). Okamoto-Mizuno et al .(1999) reported almost a regular incremental
gradation in Tc (mean, min & max) with gradual increase in temperature and humidity
and a significantly higher Tc at 35/75 and 35/50 compared with 29/50 and 29/75 during
sleep. Tsk (1–1.5ºC through out) and whole body sweat loss (two fold) was significantly
higher at 35/50 and 35/75 than at 29/50 and 29/75. Tc was higher at 35/75 than 35/50
implying that Tc during sleep is affected both by ambient temperature and relative
humidity and the modulatory effect of humidity on Tc being limited and/or more
pronounced at higher ambient temperature.
Okamoto-Mizuno, Tsuzuki, Mizuno (2005) showed that the effect of humid heat
on Tc, Tsk, mean values of clothing microclimate temperature, clothing microclimate
humidity and whole body sweat loss are almost proportionate to duration of exposure.
Tsuzuki et al. (2008) reported that Tc, Ts (Forehead, Chest, Arm, Thigh, & Foot),
clothing microclimate temperature and clothing microclimate humidity increased
significantly in warm humid climate (32/80) in comparison with thermo-neutral condition
(26/50). Ts (X and or Y) means local skin temperature of the body part X and or Y.
Airflow decreased Tc, Ts (arm, leg and foot) and the clothing microclimate humidity
significantly in humid heat but still had significant differences with respect to thermo-
neutral condition. The body-mass loss increased significantly with humidity and
temperature (32/80) and airflow significantly decreased body mass loss. Body mass loss
is the same parameter as whole body sweat loss used by Okamoto-Mizuno et al. (1999)
and calculated from the loss of weight before and after sleep i.e whole body sweat loss/
body mass loss=W before sleep-W after sleep. Okamoto-Mizuno et al. (2003) reported
that Tc, Tsk, and the local Ts (arm, thigh, forehead, chest, leg and foot) was significantly

9
higher at 32/80 and 32/80 HC (head cooling) than at 26/50. The Ts (neck) was
significantly lower at 32/80 HC than at 32/80 and 26/50. The whole-body sweat loss and
Ts (tympanum; after sleep) was significantly lower at 32/80 HC than that at 32/80 and
higher than at 26/50. The microclimate of the chest area, the relative and absolute
humidity at 32/80 was higher than at 32/80 HC and 26/50. Tsuzuki et al. (2004) also
described similar results with Ts (forehead, arm, thigh, calf and foot), Tc, clothing
microclimate temperature and humidity, Heart rate and over all sweat loss (over all sweat
loss =whole body sweat loss or body mass loss divided by body surface area =Wbefore
sleep-Wafter sleep / body surface area) higher at 32/80 than at 26/50. Okamoto-Mizuno
et al. (2004) reported that Tc decreased significantly at 26/50 in comparison to 32/50 with
sleep onset and progression. Tc gradually decreased by 0.3–0.4ºC at 26/50, while at
32/50, it initially increased then showed only a 0.1–0.2 ºC decrease. The Tsk and Ts
(arm, foot, forehead, hand and thigh) were significantly higher at 32/50 than at 26/50.
Okamoto-Mizuno and Tsuzuki (2010) working on healthy elderly population reported
that Ts (chest, thigh, foot and leg) followed the trend; winter>fall>summer, while Ts
(forehead) showed the reverse order. The temperature and RH characteristics of the
seasons during the study were as; winter (9.5±0.69 ºC & 59.9±1.60 % RH), fall
(15.4±0.25 ºC & 69.2±2.11 % RH) and summer (27.7±0.63 ºC & 74.0 ±1.89 % RH).
Though, the results seem to vary with the consensus line but there are important
differences on count of clo values (clothing insulation index; 1 clo=0.88m²·K/W),
coverings used, usage of air conditioning, light exposure etc. which may have
confounded the results.
5. Hypotheses on the effect of humidity and temperature on sleep
5a.Synchronic-Diachronic stress model
Buguet et al. (1998) proposed that environmental stimuli including humidity mediated
heat stress has two types of responses, synchronic and diachronic responses on sleep
structure depending on individual’s reactions to strain. The acute and chronic heat
stresses have different effects on sleep architecture involving different pathways. Acute
heat stress elicits somatic stress reaction leading to diachronic decrease in TST and SWS,
often accompanied by synchronic decrease in REM sleep as well (Buguet et al. 1998,
Buguet 2007). The diachronic effect is mediated by neurogenic adaptive pathways
involving limbic system processors while synchronic response is affected through
Hypothalamic-pituitary-adrenal axis activation involving stress hormone increase
(Herman and Cullinan 1997). The chronic heat stress/moderate heat stress or gradually
increasing seasonal heat acclimatization elicits neurogenic stress reaction leading to
diachronic SWS increase and/or REM increase through moderate Hypothalamic-
pituitary-adrenal axis activation as well (Buguet et al. 1998, Buguet 2007). The
hypothesis has limitations in explaining acute humid heat at night eliciting synchronic
SWS reductions (Okamoto-Mizuno et al. 1999, Buguet 2007). However, this is the only

10
hypothesis making a mention about a non-synchronic precipitation of effect (sleep
parameters) with the inducer.
5b. Central thermoregulatory-peripheral temperature mechanism interaction
The neuronal centres involved in sleep regulation have neurogenic projections/ inputs
from central thermoregulatory centres (hypothalamus) and peripheral temperature
receptors. Sakaguchi et al. (1979) hypothesized that this anatomical link has functional
implication in sleep structure regulation. It doesn’t take into account the
neuronal/neurohumoral aspect of circadian as well as homeostatic modulation, which are
established and important elements of sleep structure regulation (van Someren 2000,
2003, 2004, 2006; Dijk and Franken 2005; Saper et al. 2005, 2010) and therefore has
limitations in explaining important aspects of sleep structure regulation.
5c.Non-specific effect
Okamoto suggested involvement of non-specific effect to explain decreased REM and
SWS at 35/75 condition (Okamoto-Mizuno et al. 1999). However, humid heat exposure
was acute in their study and continuous heat exposure with contrivances to reduce stress
of acute high temperature doesn’t show SWS decrease (Libert et al. 1988). Moreover,
author themselves argue in another publication that as minor changes in ambient
temperature in thermal neutral zone may affect REM (Muzet et al. 1983) and there is
involvement of central thermoregulatory mechanisms in sleep structure regulation
(Sakaguchi et al. 1978) therefore, a non-specific effect may not be the only effect on the
sleep stage changes.
5d. Homeostatic- circadian drives interaction
Based on his seminal experiments, Borbély (1980, 1982) postulated a two-process model
of sleep regulation and later extended his concept to human sleep as well. Later, Daan S
et al. (1984) formulated a quantitative model which is the most comprehensive and
accepted model, the same had been extrapolated and extended upon by many workers.
(For further information the interested reader is referred to Borbély AA, Achermann P
1999. Sleep homeostasis and models of sleep regulation. J Biol Rhythms.14(6):557-568.)
The homeostatic sleep drive, which is predominant in the regulation of SWS, is greatest
at sleep onset and facilitates sleep during the first half of the night. Circadian drive,
which is predominant in REM regulation, becomes most marked in the latter phase of
sleep and maintains elevated sleep drive through the end of the sleep period (Czeisler and
Khalsa 2000). Humid heat affects SWS comparatively more than REM (Table 1) and
therefore seems to affect more of homeostatic drive than circadian drive. However, REM
is also under homeostatic regulation though this aspect is less dominant than circadian
(Wurtz and Edgar 2000). This diminished level of REM homeostasis may account for the
effect, though smaller on REM under humid heat condition (Table 1) outcome section.

11
McEwen (2000) defined that stressful situations, such as confronting a predator,
hostile conspecific, encountering a potential mate, seasonal changes, migration etc. as
allostatic load and Palchykova et al. (2003), Rattenborg et al. (2004), Saper et al. (2005,
2010) proposed that they may be involved in sleep structure regulation. Saper et al.
(2010) also summarized that allostatic regulation involves dual activation of the wake and
sleep circuitry, sleep state misperception and that excessive homeostatic sleep drive may
overcome allostatic driven wakefulness. A more detailed and comprehensive account of
allostatic sleep behavior is available in Saper et al. (2005, 2010). Saper et al. (2010) had
given account of the neuroanatomical, neurophysiological basis of allostatic regulation
but its interplay with thermoregulatory circuitry is almost not researched.
6. Neurophysiology of humidity effect on sleep
The neuro-humoral dimension of sleep state probability regulation is a comprehensively
established area (Stiller and Postolache 2005; Stenberg 2007; Steiger 2007; Kotronoulas
et al. 2009; Shechter and Boivin 2010). In the absence of efferent neuronal transmission,
neuro-humoral component can control circadian locomotor rhythms at least in part-the
evidence may give some elementary understanding of functional interplay between
neuronal and neuro-humoral component of the circadian system in sleep regulation as
well (Stiller and Postolache 2005). Future animal model based research with disrupted
efferent neuronal transmission and the subsequent role of neuronal component of
circadian system in sleep regulation is needed to objectively define the interplay. The
various hypothalamic-pituitary-end-organ/gland axes and their hormonal signals are
mainly relayed in a rhythmic secretory pattern (frequency modulation of signal), being
energetically more efficient than the alternatives (modulation of signal by amplitude or
by total area-under-curve). It would be interesting to explore this in case of adenosine in
basal forebrain (homeostatic regulation of sleep), because this has been suggested to be
central to mammalian sleep homeostasis (Gan and Quinton 2010). Shechter and Boivin
(2010), Saper et al. (2005, 2010) reviewed that the prominent sleep promoting neuro-
anatomical connectivity is SCN-ventral subparaventricular zone-dorsomedial nucleus of
the hypothalamus- ventrolateral preoptic (VLPO) nucleus, whereas SCN-dorsal
subparaventricular zone-dorsomedial nucleus of the hypothalamus-lateral hypothalamic
neurons is wake promoting (Shechter and Boivin 2010). The reader is referred for more
comprehensive account of the neuro-anatomy of sleep regulation to Stiller and Postolache
(2005), Aloe et al. (2005), Franks (2008), Saper et al. (2005, 2010) and Stenberg (2007).
Humid heat or the heat stress thereof has been reported to decrease NREM
(SWS), TST, SEI, and increase WASO and sleep latency (Table 1; outcome section). As
NREM sleep is under homeostatic regulation and REM predominantly has circadian
element. It therefore seems that humid heat affected more of homeostatic than circadian

12
mechanism of sleep structure regulation (Okamoto-Mizuno, Tsuzuki, Mizuno, Iwaki
2005). The marker and mechanism for this homeostatic component remain unclear (Saper
et al. 2005, 2010) and Krueger (2008) asserted that adenosine may not account for
homeostatic drive alone and therefore there is a continued hunt for additional sleep-
promoting factors. However, there is suggestive evidence implicating adenosine and
basal forebrain in homeostatic regulation (Porkka-Heiskanen et al. 2002; Aloe et al. 2005;
Saper et al. 2005, 2010). Adenosine is a product of neuronal energy metabolism at the
cellular level, accumulates in the synaptic cleft during wakefulness and has been
proposed as a homeostatic accumulator of the need to sleep (Radulovacki et al. 1984;
Benington and Heller 1995; Strecker et al. 2000; Porkka-Heiskanen et al. 2002).
Similarly, Kong et al. (2002) reported that waking decreases the main brain energy
reserve (glycogen granules) in the astrocytes-the primary brain energy storage site. This
may lead to an increase in the extracellular adenosine with consequent sleep promotion.
Halassa et al. (2009) showed that genetic deletion blocking astrocyte mediated adenosine
rise also prevented rebound recovery sleep after sleep deprivation (SD). However,
rebound recovery sleep after SD/prolonged wakefulness and its decrease over sleep
period (Achermann and Borbely 2003) do suggest that the SWS is homeostatically
controlled and reflects sleep drive (Vyazovskiy et al. 2009; Machado et al. 2010).
Further, it had been shown by micro-dialysis studies that the basal forebrain region cells
are the largest local accumulator of adenosine during wakefulness and sleep deprivation
(Porkka-Heiskanen et al. 2002). Furthermore, injection of adenosine/adenosine A1
receptor agonist into the basal forebrain of cats (Strecker et al. 2000), or an adenosine
A2a receptor agonist near the VLPO nucleus in rats, causes sleep; the latter also results in
expression of Fos (a marker of neuronal activity) in VLPO neurons (Scammell et al.
2001).
The local inhibitory action of adenosine occurs in specific adenosine-1 auto-
receptors of cholinergic cells in the basal forebrain. This blocks inhibition of GABAergic
cells in the VLPO and stimulation of the hypocretin system (Figure 2) (Alóe et al. 2005;
Saper et al. 2001, 2005, 2010). All this in conjunction with the SCN effect trigger NREM
sleep initiation as shown in (Figure 2) (Saper et al. 2001; Porkka-Heiskanen et al. 2002;
Alóe et al. 2005). [Interested reader is referred to Alóe et al. 2005, Saper et al. 2005,
2010]. Humidity because of its detrimental effect on NREM (SWS), TST, SEI, and
increasing effect on WASO and sleep latency (Table 1) may have decreasing effect on
adenosine level in basal forebrain region (this remain to be experimentally proven).
Humid heat may be implicated in adenosine decrease by disrupting circadian pattern of
heat distribution and concomitant modulation of thermo-sensitive neurons in basal
forebrain (Van Someren 2000) and/or by altering the rate of Ts change and may therefore
by affecting Ts change mediated sleep regulation (van Someren 2003, 2004, 2006;
Raymann et al. 2005, 2008; Fronczek et al 2006, 2008, Raymann and Van Someren
2008). This may effect local auto-receptor adenosine mediated cholinergic cell inhibition

13
of basal forebrain disrupting inhibition of GABA-ergic cells in the VLPO and stimulation
of the hypocretin system eliciting experimentally observed effects on sleep indices. It
would also be interesting to investigate whether the homeostatic dynamics of
thermoregulatory mechanism (Morrison and Nakamura 2011) and sleep-thermoregulation
interaction (Sawka et al. 1984; Rechtschaffen and Bergmann 2002; Palma et al. 2009;
Oliver et al. 2009; Krauchi and Deboer 2010) has anything to do with sleep homeostasis.
7. Thermo-physiology of humidity effect on sleep
The body temperature shows a circadian rhythm independent of the sleep-wake rhythm
(Aschoff 1969, 1983) but, had been linked intimately to the sleep-wake cycle (Okamoto-
Mizuno et al. 1999, 2003; Okamoto-Mizuno, Tsuzuki, Mizuno, Iwaki 2005; Okamoto-
Mizuno, Tsuzuki, Mizuno 2005; Tsuzuki et al. 2004, 2008; Okamoto-Mizuno and
Tsuzuki 2010). Prolonged sleep loss impairs temperature control (Rechtschaffen and
Bergmann 2002) and SD studies have shown hyperthemic result (Sawka et al. 1984;
Palma et al. 2009; Oliver et al. 2009) though, Vaara (2009) had reported decreasing effect
on temperature (measured from ears) with a 60 hour SD protocol. Whatever may be the
nature of the effect, the presence of effect in conjunction with above observations point to
two directional sleep-body temperature regulation dynamics (figure 4) though, more
studies with other sleep loss models will make the picture still clearer.
Morrison and Nakamura (2011) summarized the functional organization of the neural
pathways of receptors, processor and effector circuit of thermal regulation during high
ambient temperature and inflammatory challenge (figure 3). Mcallen et al. (2010)
reviewed on the basis of skin cooling experiments on anaesthetized rats that multiple
thermoregulatory control loops with distinct receptors, processors and effectors exists.
The thermal thresholds of receptors and the consequent responsiveness are quite
different. Though, there are variations in reports as regards the minor details of the
branching and/sub-branching of the receptor (and/or afferents)-processors (neural
centres)-effectors (efferents) but the basic elements of the circuit are established (Krauchi
and Deboer 2010; Shechter and Boivin 2010; Mcallen et al. 2010; Morrison and
Nakamura 2011).
Pre-optic area showed lower, but significant, melatonin receptor content with
saturation and competition studies revealing that these binding sites were of high affinity,
low capacity and high specificity. The finding may have functional neuro-humoral
implication for SCN-pre-optic area connectivity in circadian-sleep-thermoregulatory
circuit. SCN has neuro-anatomical connectivity with MPO (medial preoptic area) in pre-
optic area through dSPZ (Saper et al. 2005, 2010; Shechter and Boivin 2010). Krauchi
and Deboer (2010) rewieved that anatomical and neuro-physiological studies showed that
the pre-optic-anterior hypothalamus is the main integrator of sleep and thermoregulatory
information. The neuro-anatomical interconnection between SCN (the master clock

14
responsible for body temperature circadian rhythmicity) (Krauchi and Wirz-Justice
1994), and the VLPO of the anterior hypothalamus as well as several other brain
structures participating in the regulation of sleep and wakefulness are well documented
(Van Someren et al. 2002; Saper et al. 2005, 2010; Shechter and Boivin 2010). The SCN,
VLPO and MPO (a key thermoregulatory centre) are connected by the subparaventricular
zone and the dorsomedial nucleus of the hypothalamus (Van Someren et al. 2002; Saper
et al. 2005, 2010; Shechter and Boivin 2010).
Van Someren (2000) and Gilbert et al. (2004) proposed that circadian alterations
in the distribution of heat over the body may explain the circadian modulation of sleep-
state probability. The rhythms in core body temperature and skin temperature at the
extremities could modulate the neuronal and behavioural activation state by
synchronization/desynchronization of thermo-sensitive neurons in brain areas implicated
in sleep-arousal regulation. Ts also seems to modulate sleep-regulating systems (Van
Someren 2000, 2003, 2004) and the consequent elaboration by Van Someren (2004,
2006) that circadian/behavioural characteristic of neuroral/neuro-humoral input (sleep
propensity) are mediated by subtle Ts change, which itself has both circadian and
behavioural features (Van Someren 2004; Raymann et al. 2008; Raymann and Van
Someren 2008). The assertion is backed by neuro-biological findings, modeling studies
(Van Someren 2000) as well as recent human experimental findings (Raymann et al.
2005, 2008; Fronczek et al. 2006, 2008; Raymann and Van Someren 2008). Raymann et
al. (2008) making use of a thermosuit to control skin temperature during nocturnal sleep
demonstrated that induction of positive Ts change of mere 0.4ºC without altering Tc
suppressed wakefulness (P<0.001) and shifted sleep to deeper stages (P<0.001) in young,
elderly healthy and insomniac participants. The strongly significant sleep effect among
elderly (attenuated behavioural response to suboptimal ambient temperature) highlight
the behavioral characteristic of subtle Ts change’s effect on sleep. The studies on
narcoleptics associated with increased distal-proximal temperature gradient (Fronczek et
al. 2006) also assert about the behavioural aspect of Ts change’s effect on sleep
(Fronczek et al. 2006, 2008).Therefore, Ts change feedback (with circadian and
behavioural features) also plays a role in sleep regulation. All this in normal situations,
result in a maximal probability for sleep onset near the peak in skin temperature at the
extremities, which is closely related to the maximal rate of change on the decreasing
portion of the core temperature rhythm. The evaporative heat loss decrease (high humid
heat condition) with the net disruption of core-periphery-environment heat transfer may
affect the thermoregulatory signal component of sleep regulation suggested by Van
Someren (2000) (Figure 4) and/or rate of Ts change by alterations in coefficients of heat
transfer at the skin (Van Someren 2003, 2004, 2006; Raymann et al. 2005, 2008;
Fronczek et al 2006, 2008; Raymann and Van Someren 2008). This may explain the
temperature indices (Tc, Ts) and sleep indices co-relationship observed under humid heat

15
condition (Okamoto-Mizuno et al. 1999, 2003; Okamoto-Mizuno, Tsuzuki, Mizuno,
Iwaki 2005; Okamoto-Mizuno, Tsuzuki, Mizuno 2005; Tsuzuki et al. 2004, 2008).
Conclusion
The six important human thermal sensation and comfort defining factors should be
regulated and monitored during future sleep studies for more objective conclusion
derivation. Humidity at high ambient temperature disturbs sleep because of negative
effect on evaporative heat loss. The studies with air current and head cooling did show
that with evaporation being down regulated, the manipulations to revert the convective
and/or conductive heat transfer can help in sleep management. The expression of humid
heat effect may have both homeostatic and circadian dimension and therefore future
research to decipher the neuro-physiological basis should try to look it both ways. The
areas of peripheral detection (humidity) and the consequent neuro-anatomical, neuro-
physiological and thermo-physiological basis of humid heat effect translation in terms of
sleep/temperature indices do need further research. The polysomnographic sleep studies
do have limitations with sample size management because of temporally bigger
involvement of volunteers. Therefore, there should be some strategic innovation for
significance establishment of humid heat effect on sleep. This may be achieved by more
studies on other demographics of population, age groups and variations in study designs.
Acknowledgements:
The work was funded by Indian Council of Medical Research in the form of SRF to Md.
Dilshad Manzar and University Grant Commission in the form of Project Fellowship to
Mani Sethi. Authors also wish to acknowledge assistance by Bablu, an architect with
diagram work.

16
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Figure Caption(s)
Figure 1. Showing gradation of humidity on sleep indices with increasing relative
humidity and temperature. The condition a, b, c and d represent 29/50, 29/75, 35/50 and
35/75. [Drawn from data in table 1 in Okamoto-Mizuno K, Mizuno K, Michie S, Maeda
A, Iizuka S. 1999. Effects of humid heat exposure on human sleep stages and body
temperature. Sleep. 22 (6):767-773.]
Figure 2. Prospective role of adenosine in NREM sleep switch. The absence of excitatory
stimuli from the suprachiasmatic nucleus (SCN), the basal forebrain and the limbic
system (white arrows) as well as the inhibitory projections (coloured arrows) from the
VLPO (ventrolateral preoptic nucleus) to the hypocretin system, induce NREM sleep.

24
Where, DR=Dorsal raphe nucleus, PPT=Pedunculopontine tegmental nucleus, VTA=
Ventral tegmental area, LC= Locus Coeruleus, DRN= Dorsal raphe nucleus, TMN=
Tuberomamillary nuclei, Ach= Acetylcholine, DA= Dopamine, NA= Noradrenalin, 5-HT
= Serotonin, His= Histamine, GABA=Gamma-Aminobutyric acid. [Modified with
permission from Alóe et al. 2005. Sleep-wake cycle mechanisms. Rev Bras Psiquiatr, 27
(Suppl 1), 33-39.]
Figure 3. Showing the basic elements of thermoregulation circuit.
Where, the afferents (receptors and/or sensors) are the physiological parallels of Ts/Ta
(ambient temperature), the neural centres involved in temperature regulation (multi-
processors) and peripheral/proximal effectors are the physiological parallels of Ts/Tc.
Figure 4. Sleep structure regulation model proposed by (Van Someren 2000) with
author’s modification to incorporate humidity effect. [Van Someren, E.J., 2000. More
than a marker: interaction between the circadian regulation of temperature and sleep, age-
related changes, and treatment possibilities. Chronobiol Int, 17(3):313-354.]

dSPZ-SCN
Receptor / Sensor
= Physiological
Parallels of Ts/Ta
Multi-effector
= Physiological parallels of Ts/Tc
Multi processor
Dorsomedial
hypothalamus
MPO
Preoptic Area
Premotor neurons
(Rostral
ventromedial
medulla) +
Raphe Pallidus
Vasoconstriction Cutaneous circulation for heat loss,
Brown adipose tissue
Skeletal Muscle, Heart for
Thermogenesis, Evaporative heat
+
+
_
Thermal cutaneous
receptors,
Spinal Dorsal horn
neurons,
Lateral parabrachial
nucleus neurons
Ts

Humid heat
Circadian
modulation
Homeostatic
modulation
Allostatic
modulation
Sleep State Probability
in brain structures
involved in sleep
regulation
Thermoregulation
Subtle Ts change
Effect
─
+
Neuronal
Neurohormonal
Humid heat
+

Table1. Comparative summarization of sleep studies with humidity as parameter
Author Okamoto-Mizuno
et al. Okamoto-
Mizuno et al. Okamoto-
Mizuno et al. Okamoto-
Mizuno and
Tsuzuki
Buguet A Okamoto-
Mizuno et al. Tsuzuki et al. Tsuzuki et al.
Okamoto-
Mizuno et al.
Subject
(number,
gender, age)
Healthy
8M/8M
25±3.77 yr,
26.2±3.31 yr
Healthy 8M
25.0±3.8 yr
Healthy 7M
22.7±1.63 yr Healthy M/F-
13/6
65.8±2.6 yr
28; 11+17
Healthy 9M
25 ± 3.77 yr
Healthy 9M/8M
25±3.8 yr,
26.2±4.5 yr
Healthy 9M
25±3.8 yr
Healthy 10M
69.2 ±1.35 yr
Study design
single blind
random cross over
single blind
random cross
over
single blind
random cross
over
longitudinal observational single blind
random cross
over
single blind
random
counterbalance
cross over
single blind
random
counterbalance
cross over
single blind
random
counterbalance
cross over
Measurement
s PSG, Tre, Ts, Tsk
1
,
Tcm, Hcm
PSG, Tre, Ts,
Tsk
1
, Tcm ,
Hcm
PSG, Tre, Ts,
Tsk
1
Actigraphy, Tre,
Ts, Tsk
1
, Micro
T/H
PSG
PSG, Tre, Ts,
Tsk
1
, Tty, Micro
T/H
PSG, Tre, Ts
Tsk
1
, Micro T/H
PSG,Tre, Tsk
1
,
Ts, Tcm, Hcm,
aMT6s
PSG, Ts, Tre, Tsk
2
Intervention partial humid heat humid heat humid heat humidity,
temperature(sea
sonal variation)
11 in HHC &
17 in DC head cooling air flow, humid
heat humid heat mild heat
T &RH
26/50-32/80(26-
32),
32/80-26/50(32-
26), 26/50(26)
26/50(C),
32/80(H)
26/50-32/80(C-
H)
29/50, 29/75,
35/50,
35/75
27.7±0.63/74.0
±1.89(S),
15.4±0.25/69.2±
2.11(F),
9.5±0.69/59..9±
1.60(Win)
28–31/80-90
(HHC), 26–
28/60(DC)
26/50, 32/80,
32/80 with
cooling pillow
(32/80 HC)
26/50; 0.2 m/s,
32/80; 1.7 m/s,
32/80; 0.2 m/s
26/50, 32/80 26/50, 32/50
Time 23:00-02:45
&3:15-7:00 23:00-7:00 23:00-07:00 natural exposure
(not controlled) natural exposure
(not controlled) 23:00-07:00 23:15-07:15 23:00-7:00 22:00-06:00
Outcome: WASO: 32-26>26-
32>26
SEI: 26>26-32≈32-
26
Tcm, Hcm:
significant
interaction with
SEI, SWS (1
st
3.45 hr): C≈C-
H>H
W(total), W &
stage1(1
st
3.45
hr),Tcm, Hcm:
H >C-H≈C
SEI, SWS:
29/50 >29/75>
35/50> 35/75
Stage W, Tre:
29/50< 29/75
<35/50 <35/75
Stage 3,REM:
SEI, TST,
Ts(c/t/f/l):
Win>F>S
SL, W, Ts(fh):
S>F>Win
Significant
correlation of
Stage1, REM
DC>HHC
SWS:
HHC>DC
W, Tsk
1
, Tre, Ts
(a/t/fh/c/l/f):
26/50<32/80≈32
/80HC
WBSL,
Ts(n/ty):
32/80>32/80HC
>26/50
significant
reduction of W,
Ts (a/l/f), Tsk
1
,
Tre, WBSL and
increase of
TST, Stage 4,
stage 1, stage
W, MT, Tsk
1
,
Tre,
Ts(a/t/f/fh/calf),
Tcm, Hcm, over
all sweat loss:
32/80 >26/50
SEI, Stage 2 &
W, Tre, Tsk
2
,
Ts(a/f/fh/hand/t)
:32/50>26/50
SEI, REM:
26/50>32/30.

condition
W(2
nd
3.45 hr)
C–H≈H >C
Tsk
1
,Tre &
WBSL: H>C–
H>C
29/50> 29/75≈
35/50> 35/75
WBSL: 29/50
≈29/75<35/50≈
35/75
Tsk
1
with SEI,
WASO, Longest
wake episode
SWS in a warm
humid climate
4, aMT6s:
26/50>32/80
Where, W=wakefulness, SL=sleep latency, SEI; SWS; WASO; TST; Ts= same as in text,
Ts(a/t/l/f/fh/c/n/ty)=arm/thigh/leg/foot/forehead/chest/neck/tympanum skin temperature, Tre=rectal temperature, WBSL=whole-body sweat loss,
Clothing microclimate temperature/humidity inside pajamas & chest area =Tcm/Hcm & Micro T/H, Winter=win, summer=S, fall=F, dry
condition=DC, hot humid condition=HHC, aMT6s= 6-sulfatoxymelatonin, Tsk
1
/Tsk
2
=Mean weighted skin temperature calculated according to
Ramanathan from Ts (a/c/t/l/f)
1
/ according to Hardy and DuBois from Ts (hand/a/c/t/l/f/fh).
2
1. Ramanathan NI. 1964. A new weighting system for mean surface temperature of the human body. J Appl Physiol. 19(3):531-533.
2. Hardy JD, DuBois EF. 1938. The technique of measuring radiation and convection. J Nut. 15(5):461–475.