Running head: SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL WHEN RETURNING
TO SLEEP
By
AUTRI NICOLE HAFEZI
____________________
A Thesis Submitted to The Honors College
In Partial Fulfillment of the Bachelor’s Degree
With Honors in
Neuroscience and Cognitive Science
THE UNIVERSITY OF ARIZONA
MAY 2016
Approved by:
_____________________________________
John J.B. Allen, Ph.D.
Department of Psychology
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
2
Acknowledgments
The author was mentored by Spencer C. Dawson and Professor John J.B. Allen, both of whom
provided extensive guidance (and a sense of humor) throughout the entire project. This project
was also supported in part by the University of Arizona GPSC grant RSRCH-512FY’15 to SCD.
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
3
Abstract
Insomnia is among the most common health problems and is associated with lower
parasympathetic control. Sleep reactivity is associated with development of chronic insomnia.
The purpose of this study was to examine whether sleep reactivity is associated with
parasympathetic control in response to a sleep-relevant stressor. Parasympathetic control was
operationalized using respiratory sinus arrhythmia (RSA). Sleep reactivity was operationalized
as a score of 14 or higher on the Ford Insomnia Response to Stress Test (FIRST). Participants
were 33 healthy young adults required to adhere to a fixed eight-hour sleep schedule for three
nights before an in-laboratory sleep study. Physiological signals were recorded for two fiveminute baseline periods of resting wakefulness prior to lights out. Participants were woken after
the first five minutes of contiguous N2 sleep in the third NREM period and kept awake for 15
minutes, then allowed to return to sleep. In a multiple linear regression, the interaction between
baseline RSA and sleep reactivity predicted RSA when returning to sleep. Individuals with high
sleep reactivity had relatively low parasympathetic control when returning to sleep. People with
high sleep reactivity may benefit from interventions to increase parasympathetic control during
awakenings from sleep.
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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Background and information
Insomnia
Insomnia is among the most common health problems today and has serious
consequences (Harvey, 2001). It can be a situational, recurrent, or persistent problem. Insomnia
can also follow an intermittent pattern, presenting sleep difficulties recurrently with stressful
events. Acute insomnia is often associated with life events or changes in sleep schedule, but
typically subsides after the event subsides, but for some, the sleep disturbance persists after the
initial cause (Morin & Benca, 2012). Chronic insomnia affects approximately 30% of the
general population (Roth, 2007) and has a high rate of comorbidity with medical and psychiatric
disorders (Morin & Benca, 2012; Ohayon & Reynolds III, 2009; Roth et al., 2006; Simon &
VonKorff, 1997). Insomnia remains an important public issue because of its negative impact on
society in terms of physical and social performance, work performance, and quality of life.
Definition and criteria
The predominant complaint in insomnia remains the same across diagnostic criteria.
Diagnostic criteria include: a long-standing difficulty initiating or maintaining sleep, including
waking up too early, or non-restorative sleep or poor quality sleep, for at least three months, in
addition to daytime distress or impairment (Harvey, 2001; Roth, 2007; Roth et al., 2011;
American Psychiatric Association, 2013). These daytime consequences include fatigue, reduced
concentration and memory, irritability, and low mood and anxiety (Billiard & Bentley, 2004).
Epidemiology
Prevalence
Epidemiological studies consistently find that roughly one-third of the United States adult
population report sleep problems (Ancoli-Israel & Roth, 1999; Grandner & Kripke, 2004;
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
5
National Sleep Foundation 2005), specifically with about one-third of adults reporting insomnia
symptoms (Ohayon, 2002). As it stands, 10%-15% of the population meets the criteria for
insomnia (Breslau et al., 1996; Cirignotta et al., 1975.; Ohayon, 1996, 1997, 2002; Roth et al.,
2006) with 10%–15% experiencing associated daytime impairments (Morin et al. 2006). In
primary care settings, approximately 10%–20% of individuals complain of significant insomnia
symptoms, with overall prevalence estimates of broadly defined insomnia at approximately
23.6% in an epidemiological study (Ohayon, 2002; Roth, 2007; Roth et al., 2006, 2011).
Insomnia is a more prevalent complaint among women than among men, with a gender ratio of
about 1.41:1 (Zhang & Wing, 2006) and also has a higher prevalence among older adults (Roth,
2007). Not only are women more likely than men to have insomnia, but those that do have
higher levels of comorbid depression, but not comorbid anxiety (Taylor et al., 2005).
Comorbidities
Although insomnia can be an independent disorder, it is most frequently observed as a
comorbid condition with another medical condition or mental disorder (Roth et al., 2006; Taylor
et al., 2007). Upon analyses of available literature, people with insomnia have a higher
prevalence of comorbid medical problems than those without insomnia and people with chronic
medical problems have higher prevalence of insomnia than people without those same disorders
(Kessler et al., 2012; Taylor et al., 2007). However, symptoms of anxiety and depression that do
not meet criteria for a specific mental disorder may also be present (American Psychiatric
Association, 2013).
Among these comorbid conditions, depression and anxiety are the most common
psychiatric disorders (Harvey, 2001; Roth, 2007). A study found that 20% of people with
insomnia report clinically significant depression, making people with insomnia almost 10 times
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
6
more likely to have depression than people without insomnia. That same study found 19.3% of
people with insomnia report clinically significant anxiety, which is 17 times more likely than
people without (Taylor et al., 2007; Taylor et al., 2005). In a study of 772 people, 9.6% showed
clinically significant levels of depression, but among people in the sample with insomnia, 20%
had depression (Taylor et al., 2005). Overall, 40%-50% of individuals with insomnia present
with a comorbid mental disorder (Harvey, 2001).
Consequences
Chronic insomnia makes other disorders more difficult to treat. Chronic insomnia is
often associated with a wide range of adverse effects, including mood disturbances, difficulties
with concentration, and memory (Harvey, 2001). While treatment of the comorbid disorder may
resolve symptoms of the comorbid disorder, it does not often improve or resolve the insomnia
(Roth, 2009). In fact, insomnia complicates the primary disorder treatment with insomnia being
one of the most common residual symptoms (Benca, 1996).
People with insomnia also have a higher incidence of cardiovascular and neurologic
disease, high blood pressure, and pulmonary, urinary, and gastrointestinal problems, and chronic
pain, after controlling for depression and anxiety levels (Kessler et al., 2012; Taylor et al., 2007).
Chronic insomnia is a clinically significant risk factor associated with development of Type 2
diabetes, independent of other comorbid conditions frequently associated with insomnia and
diabetes (e.g. age, race, obesity, smoking, alcohol consumption, periodic limb movements,
depression) (Vgontzas et al., 2009). Specifically, chronic insomnia is associated with a 1.84
times higher risk of diabetes (Vgontzas et al., 2009). In another smaller study, people with
chronic insomnia and short sleep duration (< 5hours per night) as measured by polysomnography
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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had a risk of hypertension at 3.5 to 5 times higher than subjects who slept greater than 6 hours
and had no sleep complaint (Vgontzas et al., 2009).
Insomnia and treatment of Major Depressive Disorder
Insomnia is part of the diagnostic criteria for diagnosis of Major Depressive Disorder
(MDD), but insomnia might persist and is a commonly reported residual symptom even after
effective treatment and remission of depressive symptoms (Carney et al., 2007; Nierenberg et al.,
1999). Many patients with MDD who experience full symptomatic remission after
antidepressant treatment, for example Cognitive Behavioral Therapy (CBT) or
pharmacotherapies still have residual depressive symptoms (Carney et al., 2007; Nierenberg et
al., 2010). These residual insomnia symptoms that occur with a MDD episode may cause such
patients significant distress and further complicate recovery. Insomnia symptoms have also been
found to increase risk for subsequent MDD (Karp et al., 2004; Perlis et al., 1997). Variability in
residual symptoms confers greater risk for relapse and subsequent episodes, which insomnia is
among the most variable after MDD treatment (Karp et al., 2004; Paykel, 1994). Residual
insomnia rates following remission suggest that between 30 and 55% of those who recover from
depression have residual insomnia (Carney et al., 2011; Carney et al., 2007; Nierenberg et al.,
2010). Preliminary evidence shows that adjuvant treatment of insomnia can cause a greater
beneficial effect on insomnia and depression and lead to a better outcome than just treating
depression alone (Fava et al., 2006; Manber et al., 2008). Whether insomnia is co-occurring or
independent of associated problems is not always easily determined, but is critical to treatment
strategies for individual patients (NIH 2005). It is also possible that insomnia serves to worsen
and exacerbate symptoms for people with chronic illnesses (Broström et al., 2004; Taylor et al.,
2005).
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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Development of Insomnia
Age and gender are the most clearly and well-defined risk factors for insomnia as
reported by the State-of-the-Science Conference held by the National Institutes of Health in June
2005(Roth, 2007). Individuals with insomnia are also more likely to have a family history of the
disorder (Beaulieu-Bonneau et al., 2007), which suggests a genetic component, a common
environmental factor, or a learned part. However, sleep-wake regulatory gene abnormalities
have not yet been identified in insomnia (Morin & Benca, 2012). The complaint of poor sleep
and the presence of mental health problems are strong predictors of chronic insomnia compared
to physical health problems. Individuals with a history of subjective poor sleep were at
significantly higher risk of developing chronic insomnia (Singareddy et al., 2012).
Sleep reactivity
Sleep reactivity is a significant risk factor for insomnia, in part by exacerbating the
effects of stress-induced cognitive intrusions. It is also a precipitant of depression, as mediated
by insomnia (Drake et al., 2014) and is associated with polysomnographic changes in response to
stressors and subsequent development of insomnia. In 2004, Drake et al. demonstrated
vulnerability to sleep disturbance can be reliably assessed and is associated with physiological
hyperarousal as measured by heart rate. While chronic insomnia is associated with lower
parasympathetic control (Bonnet & Arand, 1998), the relationship between sleep reactivity and
parasympathetic control has not been reported. One measure of sleep reactivity is the Ford
Insomnia Response to Stress Test (FIRST; Drake et al., 2004). The FIRST has been validated by
identifying individuals at risk for disturbed sleep using polysomnography in response to caffeine
(Sheehan et al., 1998). Previous longitudinal studies have shown higher FIRST scores were
associated with increased risk of developing insomnia. This highlights the importance of
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
9
investigating the relationship between changes in stress and sleep-reactivity at the level of the
individual.
The National Sleep Foundation 2015 poll found greater stress was associated with less
sleep and worse sleep quality (National Sleep Foundation 2015). Approximately 1 in 10 people
(12%) reported severe or very severe stress in the previous 7 days and another 31% reported
moderate levels of stress. People with severe or very severe stress were getting less sleep than
they felt they need with 49 minutes less sleep per night on average. In contrast those with no or
only mild stress were only two minutes shy of their desired sleep need per night on average.
Those with severe or very severe stress were more than twice as likely to report poorer sleep
quality (very poor, poor or fair) compared with those with mild or no stress (83% v. 35%). Also,
67% of those with severe or very severe stress reported difficulty sleeping in the past 7 days
compared with only 25% of those with no or mild stress.
Currently, there is very little data directly linking vulnerability to acute sleep disturbance
to the subsequent development of chronic insomnia. Although there is a subset of individuals
susceptible to acute sleep disturbance, this characteristic may be completely coincidental and
reflect individuals with high-exposure to sleep-disruptive stressors (Drake et al., 2008). The
existing data suggest a trait of sleep reactivity to stress may exist and this predisposition is
hypothesized as genetic (Drake et al., 2008). A twin study found significant genetic influence on
three factors: insomnia, daytime sleepiness, and obesity. It showed that more than 50% of the
variance in the risk for insomnia can be attributed to genetic factors (Watson et al., 2006). This
is consistent with previous twin studies similarly demonstrating genetic factors strongly
influence insomnia. Based on this, if sleep reactivity is a significant risk factor for insomnia,
there should be significant familial aggregation of sleep reactivity (Drake et al., 2008).
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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Stress reactive insomnia
Whether accompanying another disorder or only occasional, insomnia can be influenced
by other factors like stress. In general, how individuals view stressful life events has been shown
as major factors increasing risk for insomnia (Healey et al., 1981). An individual with stress
reactive insomnia will typically have normal sleep, but can have that sleep easily disturbed in
response to stressors. Stress reactive insomnia differs from chronic insomnia in that it may last
only a single night, whereas chronic will persist for months or years. However, stress reactive
insomnia can develop into chronic insomnia (Drake et al., 2014).
Autonomic Arousal
People with insomnia show increased activation of the autonomic nervous system, which
is evidenced by physiological arousal measures including heart rate variability (HRV), metabolic
rate, body temperature, hypothalamic-pituitary-adrenal (HPA) axis activity, norepinephrine
secretion, and neuroendocrine measures (Bonnet & Arand, 1998; Bonnet & Arand, 2010;
Riemann et al., 2010). HRV provides a measure of arousal in that it is regulated by both
sympathetic and parasympathetic nervous system activities (Roth, 2007).
Parasympathetic control
Average heart rate is not a reliable measure of autonomic arousal (Bonnet & Arand,
1998; Drake et al., 2004). A more selective measure to provide this information noninvasively is
heart rate variability (HRV) which refers to the beat-to-beat changes in heart rate over time
(Kawachi, 1997; Stein & Pu, 2012). HRV results from a dynamic relationship between
sympathetic and parasympathetic nervous system influences which make up the autonomic
nervous system (ANS). This relationship can be the combined activation, combined inhibition,
or single activation/inhibition of the sympathetic and parasympathetic nervous system (Allen et
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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al., 2007). However, studies suggest the vagus nerve is implicated in HRV within the respiratory
frequency band (Allen et al., 2007; Berntson et al., 1991). High-frequency heart rate variability
(0.12-0.40 Hz), which is often referred to as respiratory sinus arrhythmia (RSA) is reflective of
overall parasympathetic control (Porges, 1995).
Parasympathetic control has not been well studied in relation to sleep reactivity. The
purpose of this study was to examine whether sleep reactivity is associated with parasympathetic
control while resting and in response to a sleep-relevant stressor (mid-night awakening).
Based on all previously discussed, hypotheses were as follows:
Study Hypotheses
Hypothesis 1: Stress-reactive insomnia will be negatively associated RSA at rest.
Hypothesis 2: Stress-reactive insomnia will be negatively associated with RSA during an
awakening from sleep.
Hypothesis 3: Stress-reactive insomnia will moderate the relationship between RSA at rest and
during an awakening from sleep, such that individuals with greater stress-reactive insomnia will
show decreases in RSA of greater magnitude than individuals with less stress-reactive insomnia.
Materials and methods
Participants and Demographics
The sample size was thirty three healthy young adults (63.6% female, mean age=20.06 ±
years, SD=2.26) meeting the below criteria.
Recruitment and Inclusion/Exclusion Criteria
Research participants were recruited through the use of advertisements and fliers posted
around the University of Arizona campus. Inclusion criteria included English as a first language,
average habitual sleep onset latency less than 20 minutes, average habitual total sleep time
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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between 5 to 9 hours, and a weeknight bedtime between 9pm and 1am. Exclusion criteria
included significant health problems, history of a head injury (i.e., loss of consciousness greater
than five minutes), sleep disorders (e.g., obstructive sleep apnea, narcolepsy), use of medication
with effects on sleep or memory (e.g., diphenhydramine), daily use of nicotine or illegal drugs
(e.g. marijuana, cocaine), history of psychiatric disorders (e.g. bipolar disorder, psychotic
disorders) and current DSM-IV Axis I disorders. Participants were asked to abstain from naps,
alcohol use, and restrict habitual caffeine use to less than two cups or glasses per day.
Measures
Stress reactive insomnia
Participants answered the Ford Insomnia Response to Stress Test (FIRST) during the
baseline and screening appointment. The FIRST is a self-assessment of vulnerability to sleep
reactivity to stress with good internal consistency. It was essential to monitoring stressproneness in certain situations affecting sleep; specifically, the self-report measures vulnerability
to stress-induced insomnia (Drake et al., 2004; Gouin et al., 2015). It is a 9-tem self-report to
measure traits of sleep reactivity in nine different situations, asking how likely a participant is to
have difficulty getting a good night’s sleep before those events. For example, one question asks
about sleep before an important meeting the next day, and another asks after watching a
frightening movie or TV show. This is to gauge likelihood of sleep disturbance even if the
individual has not experienced any situation of that sort recently (Drake et al. 2014). Sleep
reactivity was operationalized using the FIRST with a cutoff of 14 or higher identifying high
sleep reactivity.
Parasympathetic control
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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EKG methodology was used to provide information on autonomic functioning through
respiratory sinus arrhythmia (RSA) to analyze changes in heart rate before sleep at rest, at and
during awakening, while staying awake, and at return to sleep to observe how this induced-stress
reflects on parasympathetic measures. RSA is the log of the variance in the interbeat interval
(IBI) series in the frequency of respiration (0.12 – 0.40 Hz). EKG data was collected using a
modified Lead II placement with 0.3 Hz highpass and 70 Hz lowpass filters, then sampled at 400
Hz. EKG data was extracted and converted to interbeat interval. A time series at 10 Hz was then
fit to the interbeat interval series, and filtered in the respiratory frequency to pass 0.12 to 0.40
Hz. The natural log of the variance of this filtered time series was thus taken as the index of
RSA (cf. Allen et al., 2007).
Procedure
Screening and baseline
Participants were screened over the phone to determine preliminary eligibility based on
the above inclusion and exclusion criteria. During this first visit, participants provided informed
consent and began initial testing to determine further eligibility. They were screened for
presence of DSM-IV disorders using the MINI (Mini International Neuropsychiatric Interview)
(Sheehan et al., 1998). Exclusion criteria included DSM-IV Axis I classified disorders as
assessed with the MINI. They were also screened for current or past insomnia disorder as
assessed with the Duke Structured Sleep Interview and for risk of Obstructive Sleep Apnea
through the STOP-BANG and completed other measures including the FIRST. If participants
were verified to meet inclusion and exclusion criteria, they were scheduled for an overnight inlaboratory sleep study. The time scheduled was based on habitual sleep schedule and participant
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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preference with total sleeping time of eight hours and a bedtime as early as 9pm to as late as
1am.
In-laboratory sleep study
Subjects were asked to adhere to a fixed eight-hour sleep schedule at home for three days
before in-laboratory nocturnal sleep study. In order to control for extraneous influence on sleep,
participants were asked to maintain a regular bedtime between 9pm-1am and an awakening and
rise time between 5am-9am. They were also asked to abstain from napping and restrict caffeine
use to 2 cups or glasses before 12pm. To monitor compliance, participants were asked to
complete consensus sleep diaries every morning upon awakening for the 3 to 5 days prior to the
overnight sleep study. The sleep diaries include information on actual bed time, rise time, and
subjective experience of sleep (Carney et al., 2012).
Participants arrived at the laboratory 2 hours before bed-time. Sensors were affixed.
Electrodes were placed on the participant’s head according to the 10-20 electrode system at the
sites FP1, FP2, F3, F4, FZ, C3, C4, CZ, PZ, O1, and O2. Electrodes were referenced to
contralateral mastoid during data collection. Bilateral electroocculogram, submental
electromyogram, anterior tibialis electromyogram, respiratory effort (respiratory inductance
plethysmography), respiratory flow (nasal pressure transducer and thermister), hand
electromyogram (EMG), and blood oxygen were all recorded. EKG was recorded using a
modified lead II placement.
Prior to lights-out, physiological signals were recorded for two baseline periods each five
minutes long first with eyes open and then eyes closed. After baseline recordings, participants
were allowed to sleep. They were woken after five minutes of stage N2 sleep in the second
NREM period by the experimenters calling their name over the intercom.
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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RSA was derived from the electrocardiogram (EKG) and was recorded and analyzed at
multiple time points – at rest while sitting quietly before lights out for the evening, compared to
RSA at this point of sudden awakening, over the duration of the awakening, and during the
return to sleep. Participants were asked to remain awake for fifteen minutes while listening to
auditory stimuli as part of a memory test that will be reported elsewhere. If participants began to
fall asleep during this period, they were asked to remain awake. After this fifteen minute period,
participants were allowed to resume sleeping. Auditory stimuli were stopped when participants
resumed N2 sleep as evidenced by presence of sleep spindles or K complexes. Participants were
then allowed to sleep until the end of the eight hour schedule at which they were awoken and
sensors were removed. Participants were then debriefed and provided with compensation.
Results
The mean FIRST score was 14.60, SD(3.68) with a minimum reported score of 9 and
maximum reported score of 22. Of the total participants, 48.48% were above the FIRST cut-off
of 14 for high sleep-reactivity. Other descriptive statistics, including demographics,
questionnaires, and RSA variables are reported in Table 1.
Analyses will be presented organized by each hypothesis.
Hypothesis 1: Stress-reactive insomnia will be negatively associated with
parasympathetic control at rest.
There was no difference in RSA during baseline eyes open rest between those who scored
below 14 on the FIRST (M=7.05, SD=1.05) and those who scored 14 or higher on the FIRST
(M=7.02, SD=1.02), t(31)=0.09, p=0.93.
Hypothesis 2: Stress-reactive insomnia will be negatively associated with
parasympathetic control during an awakening from sleep.
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
16
T-tests showed there was no significant difference in overall RSA during the awakening
period between those who scored below 14 on the FIRST (M=66.45, SD=10.17) and those who
scored 14 or above on the FIRST (M=69.66, SD=9.22), t(31)=-0.95, p=0.35. Through the 15
minute stay awake period, there was no difference in RSA between those who scored below 14
on the FIRST (M=7.09, SD=1.36) and those who scored above 14 (M=6.88, SD=0.96),
t(31)=0.52, p=0.61. Likewise, there was no difference in RSA during the return to sleep period
between participants who scored below 14 (M=7.42, SD=1.45) and those participants who
scored above 14 (M=7.19, SD=0.91), t(31)=0.55, p=0.59. for the entire awakening period
including the stay awake time and return to sleep time, there was no difference in those who
scored below 14 on the FIRST (m=7.20, SD=1.37) and those who scored above 14 (M=7.04,
SD=0.94), t(31)=0.37, p=0.71.
Hypothesis 3: Stress-reactive insomnia will moderate the relationship between
parasympathetic control at rest and during an awakening from sleep, such that individuals with
greater stress-reactive insomnia will show decreases in parasympathetic control of greater
magnitude than individuals with less stress-reactive insomnia
In the multiple linear regression model, the relationship between baseline RSA and RSA
during return to sleep moderated by FIRST score was statistically significant, F(3, 29)=29.49.
p<.0001, R2=.75 (see Figure 1.). Higher baseline RSA predicted significantly higher RSA
during return to sleep, F(1, 29)=83.33, p<.0001. There was no significant main effect of FIRST
score on RSA during return to sleep, F(1, 29)=0.90, p=.35. The interaction between baseline
RSA and FIRST score was significant, F(1, 29)=4.25, p<.05. When returning to sleep,
participants with non sleep reactivity (FIRST scores <14) had higher RSA with values 124% of
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
17
their baseline (b=1.2372, SE=.15, t= 8.08, p<.0001), while participants with sleep reactivity
(FIRST scores >14) had RSA values 77% of their baseline (b=0.77, SE=.16, t= 4.74, p<.0001).
Discussion
The goal of this study was to examine the relationship between parasympathetic control
and sleep reactivity. This included measures of parasympathetic control during resting
wakefulness and when returning to sleep after being awoken. There were no significant
influences of sleep reactivity on parasympathetic control at rest. Similarly, there were also no
significant differences between sleep reactive and non-sleep reactive groups in their absolute
level of parasympathetic control when returning to sleep after being awoken. However, sleep
reactivity moderated the relationship between parasympathetic control at rest and when returning
to sleep. While non-sleep-reactive participants had higher parasympathetic control when
returning to sleep relative to their baseline, sleep-reactive participants had relatively low
parasympathetic control.
Sleep reactive individuals appear to decrease, rather than increase their parasympathetic
control relative to baseline when resuming sleep. These results suggest that parasympathetic
control may in part explain how sleep reactivity disrupts sleep. It extends findings about
autonomic arousal in chronic insomnia to people at risk for developing insomnia, finding that
arousal, at least in terms of parasympathetic control, may only be altered in certain situations.
Chronic insomnia and sleep reactivity are believed to show 24-hour arousal (Bonnet & Arand,
2010; Drake et al., 2006); however, the present study’s results do not show this. Rather, finding
ways of increasing parasympathetic control when returning to sleep may help prevent those with
high sleep reactivity from developing chronic insomnia. Much of the current evidence in the role
of parasympathetic control is correlative; further studies can elucidate whether arousal is causal,
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
18
coincidental or a perpetuating or predisposing factor for primary insomnia (Billiard & Bentley,
2004) because this suggests it is not a 24-hour arousal.
Implications and future directions
Parasympathetic control during the period of sleep onset and throughout the night may
prove to be an important link between stress and sleep (Drake et al., 2004). Further research
aimed at nonpharmacological and pharmacological interventions to increase parasympathetic
control can work to decrease likelihood of developing a chronic insomnia disorder and can aim
to target autonomic activity with multiple measures, rather than just RSA, and include measures
of sympathetic nervous system activity. Studies that induce experimental manipulations of
parasympathetic control would give clarity to the mechanisms underlying sleep reactivity and the
role of parasympathetic control on sleep reactivity. Participants in the current study were
primarily female. Increasing male participation, in addition to a wider age range, would provide
a more representative sample overall. In the future, rather than excluding comorbidities, specific
ones can be an examined variable. Studying the relationship between sleep reactivity and
parasympathetic tone in individuals with depression, for example, would allow for testing if the
relationship found in this study remains consistent across comorbidities. It could be interesting
to test whether sleep reactivity is associated with lower parasympathetic control while returning
to sleep among people with comorbid psychiatric disorders. Lastly, additional time points such
as a follow-up sleep study would provide information on the time-frame of sleep reactivity.
Subsequent participant follow-up would illuminate if the relationship seen between sleep
reactivity and parasympathetic tone remains constant over time, specifically if changes in RSA
precede changes in sleep or sleep reactivity, or the opposite relationship.
Limitations
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
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This study had only the single measure of autonomic activity with no other measures of
physiological arousal assessed, during a single overnight in-laboratory sleep study. The
population studied was relatively homogenous with an age range from 18 to 26 and significantly
more female than male participants. Participants were also ineligible if they had existing
comorbidities. Additionally, other studies use higher cut offs to define sleep reactivity.
Although lower cut offs for sleep reactivity are used in this study, abnormalities in
parasympathetic control are seen. If there is more of a sample with higher sleep reactivity, larger
differences may be elucidated.
Conclusion
In summary, this is the first study to examine the relationship between sleep reactivity
and parasympathetic control as measured by the FIRST and RSA in response to a sleep-related
stressor. Individuals with high sleep reactivity were shown to have lower parasympathetic
control when returning to sleep compared to individuals with low sleep reactivity. Future studies
should continue to explore this relationship and look into interventions related to and that target
parasympathetic control which perhaps may benefit those susceptible to stress-related sleep
disturbance.
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
20
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Appendix A
Table 1 – Ford Insomnia Response to Stress Test
When you experience the following situations, how likely is it for you to have difficulty
sleeping? Circle an answer even if you have not experience these situations recently.
Before an important meeting the next day
Not likely
Somewhat likely
Moderately likely
Very likely
After a stressful experience during the day
Not likely
Somewhat likely
Moderately likely
Very likely
After a stressful experience in the evening
Not likely
Somewhat likely
Moderately likely
Very likely
After getting bad news during the day
Not likely
Somewhat likely
Moderately likely
Very likely
After watching a frightening movie of TV show
Not likely
Somewhat likely
Moderately likely
Very likely
After having a bad day at work
Not likely
Somewhat likely
Moderately likely
Very likely
After an argument
Not likely
Somewhat likely
Moderately likely
Very likely
Before having to speak in public
Not likely
Somewhat likely
Moderately likely
Very likely
Before going on vacation the next day
Not likely
Somewhat likely
Moderately likely
Very likely
Drake et al., 2004
SLEEP REACTIVITY AND PARASYMPATHETIC CONTROL
28
Figure 1.
Relationship between RSA baseline v. return to sleep
RSA at return to sleep
14
12
10
8
Low FIRST
6
High FIRST
4
2
0
4
5
6
7
8
RSA at baseline
9
10
11
Table 1. Demographic and subjective sleep characteristics of study participants
Age
FIRST
RSA
baseline
RSA RTS
*p<.0001
Low FIRST
M (SD)
20.24 (2.54)
11.59 (1.42)
High FIRST
M (SD)
19.88 (2.00)
17.19 (3.08)
t value
0.45
6.77
p value
0.6549
<.0001 *
7.04 (1.03)
7.42 (1.45)
7.01 (1.00)
7.19 (0.91)
0.07
0.55
0.9429
0.5861