Cranial Manipulation Can Alter Sleep Latency and Sympathetic
Nerve Activity in Humans: A Pilot Study

MICHAEL J. CUTLER, D.O., Ph.D.,1 B. SHANE HOLLAND, D.O., M.S.,2
BERNARD A. STUPSKI, D.O., M.S.,2 RUSSELL G. GAMBER, D.O., M.P.H.,2
and MICHAEL L. SMITH, Ph.D

THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
Volume 11, Number 1, 2005, pp. 103–108
© Mary Ann Liebert, Inc.
Cranial Manipulation Can Alter Sleep Latency and Sympathetic
Nerve Activity in Humans: A Pilot Study
MICHAEL J. CUTLER, D.O., Ph.D.,1 B. SHANE HOLLAND, D.O., M.S.,2
BERNARD A. STUPSKI, D.O., M.S.,2 RUSSELL G. GAMBER, D.O., M.P.H.,2
and MICHAEL L. SMITH, Ph.D.1

ABSTRACT
Objective: To determine if cranial manipulation is associated with altered sleep latency. Furthermore, we
investigated the effects of cranial manipulation on muscle sympathetic nerve activity (MSNA) as a potential
mechanism for altered sleep latency.
Design: Randomized block design with repeated measures.
Setting: The Integrative Physiology and Manipulative Medicine Departments, University of North Texas
Health Science Center, Fort Worth, TX.
Subjects: Twenty (20) healthy volunteers (12 male, 8 female; age range, 22–35 years) participated in this
investigation.

Interventions: Subjects were exposed to 3 randomly ordered treatments: compression of the fourth ventricle
(CV4), CV4 sham (simple touch), and control (no treatment).
Outcome measures: Sleep latency was assessed during each of the treatments in 11 subjects, using the standard
Multiple Sleep Latency Test protocol. Conversely, directly recorded efferent MSNA was measured during
each of the treatments in the remaining 9 subjects, using standard microneurographic technique.
Results: Sleep latency during the CV4 trial was decreased when compared to both the CV4 sham or control
trials (p
0.05). MSNA during the CV4-induced temporary halt of the cranial rhythmic impulse (stillpoint)
was decreased when compared to prestillpoint MSNA (p
0.01). During the CV4 sham and control trials
MSNA was not different between CV4 time-matched measurements (p  0.05). Moreover, the change in MSNA
prestillpoint to stillpoint during the CV4 trial was different compared to the CV4 sham and control trials (p

0.05). However, this change in MSNA was similar between the CV4 sham and control trials (p  0.80).
Conclusions: The current study is the first to demonstrate that cranial manipulation, specifically the CV4
technique, can alter sleep latency and directly measured MSNA in healthy humans. These findings provide important
insight into the possible physiologic effects of cranial manipulation. However, the mechanisms behind
these changes remain unclear.
103

INTRODUCTION
Osteopathic physicians have practiced alternative, manual
medicine for over than 100 years. Cranial manipulation
is a subset of manual medicine, which in recent years
has been used more and more by practitioners of manual
medicine (Chaitow, 1997). An integral component of cranial
manipulation is the existence of cranial bone motion
(Sutherland, 1939). The motive force behind this motion is
referred to as the primary respiratory mechanism (PRM) and
is described as an oscillation with a frequency of 10–14 cycles
per minute (cpm) (Chaitow, 1999; Lay, 1997). Subtle
Departments of 1Integrative Physiology and 2Manipulative Medicine, University of North Texas Health Science Center, Fort Worth,
TX.
cranial motion produced by the PRM is palpable by experienced
practitioners and is referred to as the cranial rhythmic
impulse (CRI).
One of the more popular cranial manipulative techniques,
compression of the fourth ventricle (CV4), attempts to positively
influence body physiologic functioning by modifying
the rate of the CRI. During this technique the practitioner
attempts to halt the CRI (stillpoint) temporarily with
the expectation that various aspects of physiologic functioning
will move toward normalization (Magoun, 1976).
Subsequently, we have observed and others have suggested
that the CV4 technique is profoundly relaxing, often causing
patients to fall asleep during the treatment. Therefore,
we have postulated that use of the CV4 technique may decrease
sleep latency.
The autonomic nervous system plays an important role
in the regulation of sleep/wake cycles (Moldofsky and Luk,
2003). For example, recent data demonstrated a decrease in
sleep latency (more rapid onset of sleep) in norepinephrinedeficient
mice compared to normal controls (Hunsley and
Palmiter, 2003). Furthermore, Gronfier et al. (1999) demonstrated
that low neuroendocrine activity is “a prerequisite”
for an increase in slow wave EEG activity in humans. Interestingly,
it has been postulated that the CV4-induced stillpoint
is associated with decreased sympathetic tone. However,
most of the data suggesting that the CV4 technique
produces decreased sympathetic tone are limited and anecdotal.
For example, Magoun (1976) demonstrated a decrease,
compared to baseline, in electrical skin resistance after
3 minutes of CV4. He concluded that decrease in
electrical skin resistance was an indication of a decrease in
sympathetic nerve activity. Alhough this conclusion may be
accurate, it would only be an estimation of skin sympathetic
nerve activity, which is primarily involved in temperature
regulation, and not an estimation of muscle sympathetic
nerve activity (MSNA), which is a better marker of global
sympathetic activity.
The present investigation was designed to determine if
the CV4 technique is associated with altered sleep latency.
Furthermore, as a potential mechanism for altered sleep latency,
we investigated the effects of the CV4-induced stillpoint
on MSNA. We hypothesized that the CV4 technique
decreases sleep latency and the CV4-induced stillpoint is associated
with decreased MSNA.

METHODS
Subjects
This study was approved by the University of North
Texas Health Science Center Institutional Review Board.
Twenty (20) healthy volunteers (12 male, 8 female; age
range, 22–35 years) participated in this investigation. After
giving informed consent, each subject completed a medical
history questionnaire. All subjects were nonsmokers, reported
no history of cardiovascular, pulmonary, or neurologic
disease, and were not currently using medications other
than oral contraceptives. Female subjects all tested negative
for pregnancy and were not tested during menses, to eliminate
potential confounding effects of menses on fluid metabolism,
blood volume, and cardiovascular function. Subjects
were asked to abstain from vigorous exercise and
alcohol for 24 hours and caffeine for 12 hours before the
start of the study. Also, subjects were asked to maintain their
usual sleep habits (i.e., to avoid sleep deprivation) during
the week prior to participation in the study.
Sleep latency
Sleep latency was determined using standard Multiple
Sleep Latency Test protocols (Carskadon et al., 1986). Participants
were monitored as follows: electroencephalography
(EEG), C3 or C4 and O1 or O2; electro-oculography
(EOG), right horizontal or oblique, left horizontal or oblique,
and vertical; and electromyography (EMG), mental/submental.
Once the monitors had been placed, and the participant
was lying on the table, the recording devices were calibrated.
Following calibration, participants were told:
“Please lie quietly, keep your eyes closed, and try to fall
asleep,” at which time the lights were turned out (signaling
the beginning of the test). The test was terminated after 30
minutes even if the participant had not fallen asleep. Sleep
onset was defined as 3 epochs of stage 1 or 1 epoch of stage
2 sleep as scored by an independent sleep expert who was
blinded to treatment group. Sleep latency was measured as
the time from lights out to sleep onset as defined above.
Also, total percent sleep time during each trial is reported.
MSNA
Postganglionic MSNA was directly measured from the
peroneal nerve at the popliteal fossa using standard microneurographic
techniques (Valbo et al., 1979). MSNA is
reported as total activity/minute as described previously by
Smith et al. (1996).
Cardiovascular measurements
Heart rate (HR) was measured with standard limb-lead
ECG. Arterial blood pressure (BP) was measured noninvasively
with photoplethysmography at the finger (Finapres
blood pressure monitor 2300, Ohmeda, Englewood, CO).
This method has been shown to be a reliable and valid measure
of arterial BP (Imholz et al., 1988; Parati et al., 1989).
Experimental protocols
These studies were performed with subjects in the supine
position in a laboratory with an ambient temperature of
23°–24°C. Prior to the day of the experiment, subjects were
104 CUTLER ET AL.
brought to the laboratory; during this visit, subjects were familiarized
with the laboratory, completed all necessary paperwork
(consent form and medical questionnaire), and were
randomly assigned to either the sleep latency group (n 
11) or the MSNA group (n  9).
Sleep latency group protocol
On the day of the experiment, subjects were monitored
for measurement of HR, BP, EEG, EOG, and EMG. After
the monitors were in place, 5 minutes of baseline data were
recorded while the subject lay quietly in the supine position.
Subjects then underwent a sleep latency test (described
above) during each of 3 (CV4, CV4 sham, and control) randomly
ordered treatments. During the first 5–7 minutes of
the CV4 and CV4 sham trials, subjects were exposed to cranial
manipulation or touch. Conversely, during the control
trial the subject was not exposed to cranial manipulation or
touch. Each trial was separated by a 1-hour recovery period,
during which subjects were allowed to use the restroom and
move around the laboratory ad lib. Also, subjects were
blinded to which trial was the CV4 or CV4 sham treatment,
and the same practitioner performed the CV4 and CV4 sham
treatments for individual subjects.
MSNA group protocol
On the day of the experiment, subjects were monitored
for measurement of HR, BP, and MSNA. After the monitors
were in place, 5 minutes of baseline data were recorded
while the subject lay quietly in the supine position. Subjects
then were exposed to each of three randomly ordered treatments
(CV4, CV4 sham, and control). During the CV4 and
CV4 Sham trials, subjects were exposed to cranial manipulation
and touch, respectively. Conversely, during the control
trial, the subject was not exposed to cranial manipulation
or touch. Each trial was separated by a 30-minute
recovery period, during which the subjects remained in the
supine position. Also, subjects were blinded to which trial
was the CV4 or CV4 sham treatment, and the same practitioner
performed the CV4 and CV4 sham treatments for individual
subjects.
Cranial manipulation
CV4 trial. While sitting at the head of the table, the practitioner
contacted the participant’s occiput (lateral to the external
occipital protuberances, but medial to the ocipitomastoid
suture) with his or her thenar eminences. Once the
practitioner detected the CRI, the practitioner resisted the
flexion phase of the CRI and exaggerated the extension
phase. This compressive pressure was maintained until the
CRI stopped, and the stillpoint was reached. The stillpoint
was held until the CRI returned, at which point the compressive
pressure was slowly released. Finally, the practitioner’s
hands were gently removed and the participant’s
head was placed on the table.
CV4 sham trial. While sitting at the head of the table, the
practitioner lightly contacted the occiput without cradling the
participant’s head. This position was maintained throughout
the entire treatment. At the end of the sham treatment (
5
minutes) the practitioner slowly let the participant’s head
down on the table.

Data analysis
All statistical analyses were performed at a significance
level of
 0.05. Comparison of sleep latency and percent
total sleep during the CV4, CV sham, and control trials were
analyzed using one-way ANOVA with repeated measures.
MSNA, HR, and BP during the CV4 trial reflect mean values
obtained over 30-second measurement periods prior to
and during the CV4-induced stillpoint. Similarly, during the
CV4 sham and control trials, MSNA, HR, and BP reflect mean
CRANIAL MANIPULATION AND SLEEP LATENCY 105
FIG. 1. Comparison of sleep latency between CV4, CV4 sham,
and control groups (n  11). CV4  compression of the fourth
ventricle; CV4 sham  simple touch; control  no treatment.
FIG. 2. Comparison of total percent sleep between CV4, CV4
sham, and control groups (n  11). CV4  compression of the
fourth ventricle; CV4 sham  simple touch; control  no treatment.
values obtained over 30 seconds during CV4 time-matched,
prestillpoint and stillpoint measurement periods. MSNA, BP,
and HR during the prestillpoint and stillpoint were compared
using a paired-sample t-test. Comparison of the change in
MSNA (prestillpoint to stillpoint) between CV4, CV4 sham,
and control trials was analyzed using one-way ANOVA with
repeated measures. When F values revealed differences, post
hoc analysis was performed by pairwise comparison using the
least significant difference method.

RESULTS
Effect of cranial manipulation on sleep latency
As hypothesized, a significant main effect for sleep latency
between groups was observed (p
0.001). Specifically,
sleep onset was more rapid in the CV4 treatment group
(5.9  1.4 minutes) compared to the CV4 sham and control
groups (12.6  3.3 minutes and 17.2  3.3 minutes, respectively)
(Fig. 1). Additionally, a significant main effect
for total percent sleep between groups was observed (p

0.01). Both CV4 and CV4 sham groups spent a greater percentage
of time in sleep (39.1  9.2% and 44.5  10.7%,
respectively) compared to the control group (17.1  6.8%;
106 CUTLER ET AL.
FIG. 3. Thirty-second sample tracing of muscle sympathetic
nerve activity (MSNA), electrocardiogram ECG to show heart rate
(HR), and blood pressure (BP) during the CV4 trial (n  9).
CV4  compression of the fourth ventricle.
FIG. 4. Comparison of muscle sympathetic nerve activity
(MSNA) between the prestillpoint and stillpoint during the CV4
trial (n  9). CV4  compression of the fourth ventricle.
FIG. 5. Comparison of muscle sympathetic nerve activity (MSNA)
between the CV4 trial time-matched prestillpoint and stillpoint during
the CV4 sham trial (n  9). CV4  compression of the fourth
ventricle; CV4 sham  simple touch.
FIG. 6. Comparison of muscle sympathetic nerve activity
(MSNA) between the CV4 trial time-matched prestillpoint and
stillpoint during the control trial (n  9). CV4  compression of
the fourth ventricle; control  no treatment.
p
0.05) (Fig. 2). However, there was no difference in percent
total sleep between the CV4 and CV4 sham groups.
Effect of cranial manipulation on MSNA, HR,
and BP
Figure 3 is a representative tracing from one subject during
the CV4 trial comparing MSNA during the prestillpoint
and stillpoint. Consistent with our hypothesis, MSNA during
the CV4-induced stillpoint was decreased when compared
to prestillpoint MSNA; p  0.01 (Fig. 4). Conversely,
during the CV4 sham and control trials, MSNA was not different
between the CV4 time-matched prestillpoint and stillpoint
measurements; p  0.05 (Figs. 5 and 6). Furthermore,
the change in MSNA prestillpoint to stillpoint during the
CV4 trial was different compared to the CV4 sham and control
trials; p  0.05 (Fig. 7). However, this change in MSNA
was similar between the CV4 sham and control trials; p 
0.80. Finally, HR and BP were not significanly different at
any time points during all three trials; p  0.05 (Table 1).

DISCUSSION
The primary findings of the present investigation are that
cranial manipulation using the CV4 technique can decrease
sleep latency independent of touch in humans. Also, the
CV4-induced stillpoint is associated with decreased MSNA
compared to prestillpoint MSNA and this response appears
to be independent of touch in humans.
This investigation is the first to evaluate the effect of cranial
manipulation on sleep onset. Specifically, we demonstrated
that onset of sleep was more rapid following cranial
manipulation using the CV4 technique, when compared to
both sham treatment and no treatment. The mechanism for
decreased sleep latency following cranial manipulation is
not known. Recent research suggests that the autonomic nervous
system plays an important role in sleep onset. Specifically,
using power spectral analysis of heart rate, Gronfier
et al. (1999) demonstrated that decreased sympathetic nervous
system activity precedes and is likely a prerequisite for
increasing slow wave EEG activity. Additionally, Hunsley
and Palmiter (2003) established that norepinephrine-deficient
mice have decreased sleep latency after mild stress
when compared to controls. Together these studies suggest
an important relationship between the sympathetic nervous
system and sleep onset.
The current study demonstrated that the CV4-induced
stillpoint is associated with a modest decrease in MSNA. This
is consistent with previous data from Sergueef et al. (2002),
who demonstrated that cranial manipulation alters autonomic
nervous system activity. Specifically, they demonstrated that
cranial manipulation alters the thermal (Mayer) and baro
(Traube-Hering) signals from cranial bloodflow velocity
recordings, both of which are mediated through sympathetic
and parasympathetic nervous system activity. The mechanism
for the decrease in MSNA during the CV4-induced stillpoint
is not known. Similarly, how long MSNA remains decreased
is not known, as the present study did not follow
sympathetic nerve activity during recovery from treatment.
Possible limitations of our study include, first, the effect
of circadian cycles on the sleep latency test. To control for
possible confounding effects of circadian cycles, all patients
were tested during the same time of day (between the hours
of 1:00 PM and 6:00 PM). Second, our data assume the existence
of the PRM. Because of the subtle nature of these

CRANIAL MANIPULATION AND SLEEP LATENCY 107
FIG. 7. Change in muscle sympathetic nerve activity (MSNA)
from prestillpoint to stillpoint during CV4, CV4 sham, and control
trials (n  9). CV4  compression of the fourth ventricle; CV4
sham  simple touch; control  no treatment.
TABLE 1. COMPARISON OF MEAN HEART RATE (HR) AND BLOOD PRESSURE (BP) BETWEEN THE PRESTILLPOINT AND STILLPOINT
DURING CV4, CV4 SHAM, AND CONTROL TRIALS (N  9)
CV4 trial CV4 sham trial Control trial
Prestillpoint Stillpoint Prestillpoint Stillpoint Prestillpoint Stillpoint
HR 56 4 57 4 57 4 56 4 59 4 57  4
BP 90 5 91 4 92 4 91 4 92 3 91  3
CV4, compression of the fourth ventricle; CV4 sham, simple touch; control, no treatment.
phenomena, their very existence is an issue of debate (Ferre
and Barbin, 1991; Norton, 2000). However, though the underlying
mechanism of the PRM remains unclear, there is
considerable research to document the existence of the PRM,
recently reviewed by Nelson (2002). Also, similar to the
findings of Sergueef et al. (2002), our data demonstrated a
quantitative difference between cranial manipulation and
simple palpation. These findings suggest that cranial manipulation
can alter physiology; however, the mechanisms
explaining these changes remain unclear. Third, our data assume
the existence of the practitioner-perceived stillpoint.
However, the current study demonstrated a decrease in
MSNA during the practitioner-perceived stillpoint and no
difference in time-matched measurement of MSNA during
the CV4 sham and control trials. Therefore, it seems reasonable
to assume that the practitioner-perceived stillpoint
represents an actual phenomenon. Fourth, measurement of
MSNA and sleep latency was not performed in the same
subjects. This limits our ability to draw a clear mechanistic
link between decreased MSNA and sleep latency during cranial
manipulations. Nevertheless, current research has
demonstrated an apparent relationship between the autonomic
nervous system and sleep onset. Therefore, the decreases
in MSNA and sleep latency demonstrated in the current
study are likely related. However, further research is
needed to confirm this assumption.
In conclusion, the current study is the first to demonstrate
that cranial manipulation, specifically the CV4 technique,
can alter sleep latency and directly measured MSNA in
healthy humans. These findings provide important insight
into the possible physiological effects of cranial manipulation.
However, the mechanisms behind these changes remain
unclear.

ACKNOWLEDGMENTS
This project was supported in part by a research fellowship
and grant from the American Osteopathic Association:
F0-01 (MJC), 98-11-466 (MLS). The authors thank the subjects
for their cooperation and contribution to this work.
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Address reprint requests to:
Michael J. Cutler, D.O., Ph.D.
Department of Internal Medicine
MetroHealth Medical Center
2500 MetroHealth Drive
Cleveland, OH 44109-1998
E-mail: mcutler@metrohealth.org
108 CUTLER ET AL.