New insights into central cardiovascular control during exercise in humans: a

central command update

J. W Williamson, P. J Fadel and J. H Mitchell

Exp Physiol 2006;91;51-58; originally published online Oct 20, 2005;

DOI: 10.1113/expphysiol.2005.032037

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Exp Physiol 91.1 pp 51–58 51

Experimental Physiology – Neural Control of the Circulation During Exercise

New insights into central cardiovascular control during

exercise in humans: a central command update
J. W. Williamson1 , P. J. Fadel2 and J. H. Mitchell3
1
Department of Kinesiology, Health Promotion & Recreation University of North Texas, Denton, TX, USA
2
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA
3
Department of Internal Medicine, The Harry S. Moss Heart Center, University of Texas South-western Medical Center, Dallas, TX, USA

The autonomic adjustments to exercise are mediated by central signals from the higher brain
(central command) and by a peripheral reflex arising from working skeletal muscle (exercise
pressor reflex), with further modulation provided by the arterial baroreflex. Although it is clear
that central command, the exercise pressor reflex and the arterial baroreflex are all requisite
for eliciting appropriate cardiovascular adjustments to exercise, this review will be limited
primarily to discussion of central command. Central modulation of the cardiovascular system via
descending signals from higher brain centres has been well recognized for over a century, yet the
specific regions of the human brain involved in this exercise-related response have remained
speculative. Brain mapping studies during exercise as well as non-exercise conditions have
provided information towards establishing the cerebral cortical structures in the human brain
specifically involved in cardiovascular control. The purpose of this review is to provide an update
of current concepts on central command in humans, with a particular emphasis on the regions
of the brain identified to alter autonomic outflow and result in cardiovascular adjustments.
(Received 19 August 2005; accepted after revision 5 October 2005; first published online 20 October 2005)
Corresponding author J. W. Williamson: Univeristy of North Texas, College of Education, PO Box 311337, Denton,
TX 76203-1337, USA. Email: jwilliamson@coe.unt.edu

Neural control of the circulation during exercise is a
complex phenomenon involving many sites within the
central nervous system from sacral portions of the spinal
cord to higher regions of the cerebral cortex. The concept
of descending signals from higher brain centres capable
of influencing cardiovascular responses during exercise
(Johansson, 1895; Zuntz & Geppert, 1886), originally
termed ‘cortical irradiation’ (Krogh & Lindhard, 1913)
and later termed ‘central command’ (Goodwin et al.
1972), has been well studied and is widely accepted
throughout the scientific community. Most would concur
that the magnitude of central command during exercise
can be largely dictated by an individual’s perception of
effort during actual or even attempted physical exertion,
independent of the actual workload or force production
(Mitchell, 1990). While increases in an individual’s rating
of perceived exertion or effort sense during exercise
are coupled with elevated cardiovascular responses, the
specific region(s) within the higher brain responsible
for generating the neural signals resulting in autonomic
adjustments has remained elusive. It is postulated that
these signals can affect neural activity within the
thalamus, hypothalamus and mesencephalon prior to
reaching medullary regions of cardiovascular integration.
Animal investigations have employed stimulation of both
diencephalic and mescenphalic regions to represent the
descending central command signals and have provided
valuable information as to the role of central command
in cardiovascular regulation (Waldrop et al. 1996). What
remains of interest are the specific cerebral cortical regions
of the human brain activated by central command during
exercise. By mapping the human brain during exercise, it
is possible to gain further insight as to the specific regions
involved in central command or, more specifically, the
neural networks that are altered by changes in perception
of effort and result in cardiovascular adjustments.
Defining and re-defining central command
Before one can begin to discuss the functional importance
of central command and the location of the brain regions
participating in a central command response, one must
first consider how the term central command is being

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52 J. W. Williamson and others
used. The concept of central command during exercise
has been classically defined as ‘a feedforward mechanism
involving parallel activation of motor and cardiovascular
centres’. The primary focus of central command-related
investigations has been the modulation of motor effort
and the resulting alterations in cardiovascular responses.
We would contend that the cerebral cortical regions
involved in a ‘central cardiovascular command’ do
not always require the parallel activation of ‘central
motor command’ systems to exert their influence. This
contention is based on findings that indicate that the
magnitude of a central command-mediated cardiovascular
response during exercise can be independent of force
production (e.g. imagined exercise) and dictated more by
an individual’s perception of effort (see Fig. 1; Nowak et al.
1999, 2005; Williamson et al. 1999, 2001, 2002). Thus,
central command implies an ‘effort-induced modulation
of autonomic function’. Nevertheless, the classically used
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Exp Physiol 91.1 pp 51–58
terminology in reference to a parallel activation of both
cardiovascular and motor regions during exercise remains
accurate, since the activation of motor and cardiovascular
centres in the higher brain is requisite for physical activity.
However, an important finding from recent research is
that a network of structures exist that are involved in a
centrally mediated cardiovascular activation, which do
not require a parallel motor activation to exert their
influence (Nowak et al. 1999, 2005; Williamson et al.
1999, 2001; 2002). Therefore, central command during
exercise may actually involve the simultaneous activation
of two separate networks, one for central motor control
and one for central cardiovascular control. While these two
networks may interact as components of central command
during exercise, they can function independently of one
another. In this regard, we will focus our discussion
specifically on those brain regions believed to be involved
in central cardiovascular regulation.
Figure 1. Heart rate, mean blood
pressure and perceived exertion
responses during actual and imagined
handgrip exercise
Subjects with high hypnotizability exhibited
significant increases in heart rate, mean
blood pressure and perceived exertion
during imagined handgrip (right-hand side)
compared to subjects with low
hypnotizability. Importantly, muscle
electromyographic recordings demonstrated
that no measurable increases in force were
produced during imagined handgrip. The
data are presented as means ± S.D. and
significant differences between groups are
shown as ∗ P < 0.05. (Reproduced with
permission from Williamson et al. 2002.)


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Exp Physiol 91.1 pp 51–58 Central cardiovascular control 53

A second issue involving the classic definition of
central command is the term ‘feedforward’ mechanism.
Feedforward typically implies a control system operating
without continuous negative feedback. This feedforward
characterization may be largely based on the immediate
cardiovascular response to the onset (or even anticipation)
of exercise, such that there would not be sufficient time
for feedback from the periphery (i.e. working skeletal
muscle afferent signals) to reach the cardiovascular centres
in the brainstem (Johansson, 1895; Zuntz & Geppert,
1886). However, there is evidence that the effects of
central command on cardiovascular responses are closely
related to the intensity or perceived effort of the exercise
(Asmussen et al. 1965; Gandevia et al. 1993; Leonard et al.
1985), even at the onset of exercise (Smith et al. 1997).
Studies employing partial and complete neuromuscular
blockade have reported greater cardiovascular responses
resulting from a greater level of central command as
indexed by an individual’s perceived effort (Asmussen
et al. 1965; Leonard et al. 1985; Gallagher et al. 2001;
Gandevia et al. 1993). From these findings, a strong
case could be made that an individual’s perception or
sense of effort can serve as a means of ‘feedback’ to
establish the magnitude of the central command response.
Although feedback from the working muscles during
exercise may certainly modulate the central command
response, the aforementioned studies show that muscle
afferent feedback is not a requisite component of the
central command response. A key point for consideration
in human studies is that an increase in motor unit
recruitment or force production, resulting in an increased
afferent feedback, is typically coupled with increased
ratings of perceived exertion or effort. More importantly,
changes in perception of effort, even without alterations in
muscle afferent input during constant exercise, can modify
cardiovascular responses (Williamson et al. 2001, 2002).
Thus, it is the sense of effort that appears to be driving the
central command response. Therefore, we propose that
‘central command’ can function as a feedback system,
responding to an individual’s sense of effort, to elicit
proportional changes in cardiovascular responses, which
does not necessarily require a parallel motor activation to
exert its influence.
Importance of central command in cardiovascular
control during exercise
The cardiovascular and haemodynamic adjustments
to exercise are primarily mediated by alterations
in parasympathetic and sympathetic neural activity
(Mitchell, 1990). These exercise-induced changes in
autonomic neural outflow, which are designed to meet the
metabolic demands of the exercising muscle, are mediated
via multiple neural mechanisms working in concert. It is
well accepted that central command (Waldrop et al. 1996),
the exercise pressor reflex (McCloskey & Mitchell, 1972;
Mitchell et al. 1983; Kaufman & Forster, 1996) and the
arterial baroreflex (Raven et al. 1997; Fadel et al. 2004) are
all involved in mediating the characteristic cardiovascular
and haemodynamic adjustments to exercise (Fig. 2).
The importance of central command in initiating the
autonomic adjustments to exercise is further emphasized
by the key role central command plays in the resetting
of the arterial baroreflex during exercise (Gallagher et al.
2001; Querry et al. 2001; Ogoh et al. 2002; Raven et al.
2002). By using an innovative tendon vibration protocol
(Goodwin et al. 1972) to alter central command input,
Ogoh et al. (2002) recently demonstrated that the resetting
of the carotid baroreflex stimulus–response curve during
exercise could be reduced to lower pressures or increased to
higher pressures by selectively decreasing or augmenting

Figure 2. A schematic illustration of the

mechanisms of neural cardiovascular
control during exercise
Neural signals originating from the brain
(central command), the aorta and carotid
arteries (arterial baroreceptor reflex) and
skeletal muscle (exercise pressor reflex) are
known to modulate sympathetic and
parasympathetic nerve activity during
exercise. The alterations in autonomic
outflow mediate changes in heart rate and
contractility, as well as the diameter of
resistance and capacitance vessels within
various tissue beds (e.g. splanchnic region).
As a result, changes in heart rate (HR),
stroke volume (SV) and systemic vascular
resistance (SVR) mediate alterations in mean
arterial pressure (MAP) appropriate for the
intensity and modality of the exercise.

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54 J. W. Williamson and others
central command activation, respectively. These findings
confirm and extend previous studies in both animals
(McIlveen et al. 2001) and humans (Gallagher et al. 2001;
Querry et al. 2001) demonstrating that central command
is actively involved in baroreflex resetting during exercise.
Aside from its critical role in the actual resetting of
the baroreflex stimulus–response curve, central command
input appears also to be responsible for the relocation
of the operating point (prestimulus blood pressure) away
from the centring point (point at which there is an equal
depressor and pressor response to a given change in
blood pressure) and closer to the threshold of the cardiac
baroreflex stimulus–response curve (see Fig. 3; Potts et al.
1993; Gallagher et al. 2001; Ogoh et al. 2002). This effect
of central command on the operating point appears to be
mediated via vagal withdrawal associated with increases
in exercise intensity (Ogoh et al. 2005). It has been shown
to occur in order to allow the arterial baroreflex to adapt
to and potentially modify the increases in blood pressure
induced by activation of the exercise pressor reflex (Sheriff
et al. 1990; Potts & Mitchell, 1998). Thus, the relocation
of the operating point by central command may be
very important in preventing excessive increases in blood
pressure during exercise, since it places the baroreflex in a
more optimal position to counter hypertensive stimuli.
Figure 3. A schematic illustration of a baroreflex
stimulus–response curve and the resetting that occurs during
exercise, with a particular emphasis on the movement of the
operating point away from the centring point and closer to the
threshold of the curve
The centring point is the point at which there is an equal depressor
and pressor response to a given change in blood pressure, the
operating point is the prestimulus blood pressure, threshold is the
point where no further increases in heart rate are elicited by further
reductions in blood pressure, and saturation is the point where no
further decreases in heart rate are elicited by further increases in blood
pressure. This relocation of the operating point away from the
centring point and closer to the threshold of the stimulus–response
curve with increasing exercise intensity positions the baroreflex in a
more optimal position to counter hypertensive stimuli.
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Exp Physiol 91.1 pp 51–58
Functional anatomy
Based on our ‘proposed’ definition of central command, a
network of higher brain structures (or a single structure)
capable of interpreting an individual’s sense of effort and
making appropriate autonomic adjustments should be
considered within any anatomical framework. Primary
regions of the cerebral cortex with the capacity for
modulation of autonomic function have been carefully
reviewed, and it was concluded that both the insular
cortex and the infralimbic cortex, more specifically the
medial prefrontal cortex, were well suited for this role
(Cechetto & Saper, 1990; Verberne & Owens, 1998).
Efferent pathways from the insular cortex to well-
recognized sites of cardiovascular control, including
the lateral hypothalamus, rostral ventrolateral medulla
and nucleus of the solitary tract, have also been well
documented (see Fig. 4; Yasui et al. 1991). Changes in
heart rate and blood pressure have been reported in
response to activation of the insular cortex in both rats
(Ruggiero et al. 1987) and humans (Oppenheimer et al.
1992). Saper (1982) noted a convergence of autonomic
and limbic connections within the rat insula (Fig. 4).
There also exist reciprocal connections between the
insular cortex and the infralimbic cortex (medial prefontal
region), suggesting a potential for interaction between
these regions. The medial prefrontal cortex has multiple
limbic sensory inputs and appears to have a significant
role in ‘stress-related modulation’ of sympathetic outflow
(Verberne & Owens, 1998). Taken together, the insular
cortex and medial prefrontal cortex may function in
concert or independently to interpret sensory input and
elicit appropriate autonomic adjustments. It would seem
plausible to predict that these same brain regions that alter
cardiovascular responses during non-exercise conditions
could also be activated during exercise conditions.
Therefore, given the importance of the insular and
medial prefrontal regions in overall cortical modulation
of autonomic function, human studies have focused on
assessing their possible roles in central neural regulation
of autonomic function during exercise.
Neuroimaging studies
Studies investigating the functional anatomy of central
command-induced changes in regional cerebral blood flow
(rCBF) have identified a network of structures activated in
the human brain. These regions include the insular cortex
(King et al. 1999; Nowak et al. 1999, 2005; Williamson
et al. 1999, 2001, 2002; Critchley et al. 2000) and anterior
cingulate cortex or the medial prefrontal region (King
et al. 1999; Critchley et al. 2000; Thornton et al. 2001;
Williamson et al. 2001, 2002) as well as thalamic regions
(King et al. 1999; Thornton et al. 2001; Williamson et al.
2001, 2002). These structures appear to be activated in


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response to an increased perception of effort during
exercise when heart rate and blood pressure are elevated.
Focusing first on the insular cortex, it is possible that
the observed rCBF changes within the insular cortex
during exercise were related to the blood pressure increases
(Zhang & Oppenheimer, 1997) or the activation of skeletal
muscle afferents (Ichiyama et al. 2004). Although the
activation of muscle afferents can lead to rCBF changes
within specific regions of the insular cortex, insular
activation has been reported during attempted movement
in spinal cord-injured subjects when afferent feedback
was absent (Nowak et al. 2005). In addition, imagined
exercise has also been shown to cause insular activation,
but only when the imagined effort elicited cardiovascular
responses (Williamson et al. 2002). Therefore, it is likely
that there are different regions within the insular cortex
that are responsive to skeletal muscle afferent input and
to central command during exercise. In this regard,
numerous afferent and efferent connections to and from
the insular cortex have been identified in the rat brain
(Fig. 4). Of note are the primary projections from the
insular cortex to the hypothalamus, which may identify an
important linkage between the human studies focusing on
activation of the insular cortex and the animal studies using
electrical stimulation of hypothalamic or mesencephalic
locomotor regions to evoke ‘central command’-induced
cardiovascular responses.
In an attempt to localize regions of the insular cortex
responding to central command that are independent
Figure 4. A schematic diagram of a
horizontal cross-section through the rat
brain, illustrating both the afferent
inputs (left) and efferent outputs (right)
to and from the insular cortex
(Adapted from Cechetto & Saper, 1990.)


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of skeletal muscle afferent input or blood pressure
elevations, a recent study compared rCBF changes during
volitional static handgrip alone (central command/muscle
metaboreflex) and postexercise circulatory occlusion alone
(no central command/muscle metaboreflex; Williamson
et al. 2003). Blood pressures between the two protocols
were closely matched. The primary finding was that there
were distinct regions of the insular cortex and anterior
cingulate cortex activated during static handgrip exercise
by central command that were independent of muscle
metaboreflex activation or blood pressure elevations (see
Fig. 5). More specifically, the right inferior posterior
and left inferior anterior insular regions were activated
to a greater extent during exercise, but not during
postexercise circulatory occlusion with elevated blood
pressure. Findings of the left inferior anterior activation are
consistent with previous work demonstrating a significant
correlation between left inferior anterior activation and
heart rate during exercise (Williamson et al. 1999).
Careful examination of data provided by King et al.
(1999) during a brief bout of handgrip exercise identifies
that the right posterior insular region was activated
during the handgrip, but not immediately postexercise.
Critchley et al. (2000) also reported activation of the right
posterior insular region during handgrip, as well as in
response to mental stress. Insular activation during mental
stress supports the concept of similar cortical regions
modulating cardiovascular responses for both exercise
and non-exercise conditions. It should be noted that
56 J. W. Williamson and others Exp Physiol 91.1 pp 51–58

activation of the right inferior posterior insular region
was also reported to covary with blood pressure changes
(Williamson et al. 1999; Critchley et al. 2000).
With regard to a specific role of the anterior cingulate
cortex as related to central command, it is largely involved
in the discrimination of peripheral somatosensory input.
Thus, it could serve to interpret an individual’s level of
central command (or effort sense). This region, defined as
the anterior cingulate cortex by both Critchley et al. (2000)
and Williamson et al. (2003), is included within the region
termed the medial prefrontal cortex by King et al. (1999).
These investigators reported that activation of this medial
prefrontal region during handgrip exercise was associated
with cardiovascular activation. Reviews by Cechetto &
Saper (1990) and Verberne & Owens (1998) have defined
a significant role for the medial prefontal cortex in
cardiovascular regulation, and this area appears to have
a role in central command during exercise (Williamson
et al. 2001, 2002, 2003). This suggests that the anterior
cingulate cortex may work in conjunction with portions
of the insular cortex as a ‘central command network’,
functioning to interpret an individual’s sense of effort and
then eliciting appropriate autonomic adjustments to affect
cardiovascular responses.
Regions of the thalamus appear to be involved in the
pathway from higher brain regions to midbrain areas. As
noted previously, animal investigations often elicit central
command signals via stimulation of mesencephalon and
posterior hypothalamic regions (Waldrop et al. 1996).
Findings of thalamic activation coupled with that of
higher brain centres provides some indirect evidence
towards establishing a central command pathway to
brainstem structures. From human studies, activation
of the right and left inferior thalamic regions has been
reported during both handgrip exercise and postexercise
circulatory occlusion (Williamson et al. 2003). The inferior
(or ventral) region of the thalamus activated was analogous
to the ventroposterior region previously demonstrated to
have reciprocal connections with the insular cortex (Saper,
1982; Cechetto & Saper, 1990), which may be further
related to baroreceptor activation (Cechetto & Saper,
1990). Blood pressure changes have been show to elicit
activation in the thalamus (Cechetto & Saper, 1990; Zhang
& Oppenheimer, 2000). Zhang & Oppenheimer (1997)
determined that a significant portion of baroreceptor-
related neurones from the ventrobasal thalamus were
reciprocally connected with the posterior insula in the
rat. Further, it has been reported that regions of the

Figure 5. Differences in brain activation from rest for static handgrip (SHG) (left) and postexercise
circulatory occlusion (PECO; middle) matched for the same mean blood pressure elevation
Coregistered single-photon-emission computed tomography (SPECT) and magnetic resonance imaging (MRI) data
representing a transaxial slice from one subject. The coronal and sagittal MRI panels (right) show lines of orientation
for the tranasxial slice. The top and bottom of the transaxial panels correspond to an anterior and posterior
orientation, respectively. Changes in regional cerebral blood flow (rCBF) distribution from SPECT data were mapped
on the MRI by using an arbitrary colour scale with a positive range from 5 to 25% (from green through yellow
to red) and a negative range from −5 to −25% (from purple through dark blue to light blue). The white lines
denote the specific regions of interest assessed in this brain slice and encompass the right and left insular cortexes
for inferior anterior (ICia) and inferior posterior (ICip) regions, right and left inferior thalamic regions (THi), and
anterior cingulate cortex (AC). The image shows that during SHG there were significant increases in activation
for both anterior cingulate and insular regions that were not present during PECO. However, there is significant
activation in the thalamus and right inferior anterior insula during PECO, similar to that observed during handgrip.
(Reproduced with permission from Williamson et al. 2003.)

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Exp Physiol 91.1 pp 51–58 Central cardiovascular control
human ventrocaudal nucleus of the thalamus are involved
in the integration of afferent baroreceptor information
(Oppenheimer et al. 1998). When directly stimulated,
these thalamic regions can elicit increases in heart rate and
blood pressure in humans (Thornton et al. 2002). Thus,
regions of the human thalamus appear to have a key role
in the overall regulation of blood pressure via baroreflex
mechanisms and probably play a role in central command-
induced changes in baroreflex function.
Summary
The neural circuitry of central command appears to
encompass regions of the insular cortex and anterior
cingulate cortex that interact with thalamic and brainstem
structures of cardiovascular integration, although there
may be other cerebral cortical regions involved. While
we have redefined central command to imply an ‘effort-
induced modulation of autonomic function’, the classically
used terminology in reference to a parallel activation of
both cardiovascular and motor regions during exercise
remains accurate. However, it would appear that central
command can function as a feedback system, based on
an individual’s sense of effort or exertion, and does not
require a parallel motor activation to exert its influence.
Further, it is likely that the same regions of the higher brain
involved in cardiovascular modulation during exercise
are involved in cardiovascular modulation during non-
exercise conditions.
The study of central command and its functional
anatomy poses unique challenges in trying to uncouple
the role of higher brain cardiovascular centres from those
of the motor centres and the influences of working skeletal
muscle afferents and blood pressure changes during
exercise. The redundancy between central command and
skeletal muscle afferent feedback mechanisms during
exercise may be explained, at least in part, in that
an individual’s perception of effort can be largely
influenced by somatomotor sensations arising from
working skeletal muscle during exercise. These signals
may serve as some type of feedback to help gauge the
level of required effort or central command. Further, an
individual’s perception of effort, independent of afferent
feedback, such as the perception of effort occurring
during attempted exercise with paralysis, contributes
importantly to the central cardiovascular command
response.
The insular cortex and anterior cingulate cortex appear
to be capable of responding to multiple inputs. However,
comparisons regarding activation patterns between studies
are complicated by potential species differences as well
as anatomical and neurophysiological variations within
species. Human investigation is hampered somewhat in
that it is not possible to determine the specific type
of neural activity (i.e. excitatory or inhibitory) based
upon changes in patterns of brain activity. However,


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57
defining the regions involved in centrally mediated
cardiovascular modulation is of critical importance
in furthering our understanding of this concept and
may have clinical implications related to various types
of autonomic dysfunction (e.g. emotional syncope,
white coat hypertension). Future investigations must be
performed in humans to more clearly define the specific
sites within these regions responsible for changes in
autonomic function and how they interact to effectively
modulate cardiovascular responses during exercise as well
as during non-exercise conditions.
References
Asmussen E, Johansen SH, Jorgensen M & Nielsen M (1965).
On the nervous factors controlling respiration and
circulation during exercise. Experiments with curarization.
Acta Physiol Scand 63, 343–350.
Cechetto DF & Saper CB (1990). Role of the cerebral cortex in
autonomic function. In Central Regulation of Autonomic
Function, ed. Spyer M & Lowey D, pp. 208–223. Oxford
University Press, Oxford, UK.
Critchley HD, Corfield DR, Chandler MP, Mathias CJ & Dolan
RJ (2000). Cerebral correlates of autonomic cardiovascular
arousal: a functional neuroimaging investigation in humans.
J Physiol 523, 259–270.
Fadel PJ, Gallagher KG & Smith SA (2004). Neural mechanisms
influencing baroreflex resetting during exercise. Recent
Research Developments in Physiology, pp. 413–448. Research
Signpost.
Gallagher K, Fadel P, Stromstad M, Ide K, Smith S, Querry R,
Raven P & Secher N (2001). Effects of partial neuromuscular
blockade on carotid baroreflex function during exercise in
humans. J Physiol 533, 861–870.
Gandevia SC, Killian K, McKenzie DK, Crawford M, Allen GM,
Gorman RB & Hales JP (1993). Respiratory sensations,
cardiovascular control, kinaesthesia and transcranial
stimulation during paralysis in humans. J Physiol 470,
85–107.
Goodwin GM, McCloskey DI & Mitchell JH (1972).
Cardiovascular and respiratory responses to changes in
central command during isometric exercise at constant
muscle tension. J Physiol 226, 173–190.
Ichiyama RM, Waldrop TG & Iwamoto GA (2004). Neurons in
and near insular cortex are responsive to muscular
contraction and have sympathetic and/or cardiac-related
discharge. Brain Res 1008, 273–277.
Johansson JE (1895). Ueber die Einwirkung der
Muskelthatigkeit auf die Athmung und die Hertzhiitigkeit.
Skandinaviesches Arch Fiir Physiologie 5, 20–66.
Kaufman MP & Forster HV (1996). Reflexes controlling
circulatory, ventilatory and airway responses to exercise.
In Handbook of Physiology, chapter 11, section 12, Exercise:
Regulation and Integration of Multiple Systems, ed. Rowell LB
& Sheperd DT, pp. 381–447. American Physiological Society,
Bethesda, MD, USA.
King AB, Menon RS, Hachinski V & Cechetto DF (1999).
Human forebrain activation by visceral stimuli. J Comp
Neurol 413, 572–582.
58 J. W. Williamson and others
Krogh A & Lindhard J (1913). The regulation of respiration
and circulation during the initial stages of muscular work.
J Physiol 47, 112–136.
Leonard B, Mitchell JH, Mizuno M, Rube N, Saltin B & Secher
NH (1985). Partial neuromuscular blockade and
cardiovascular responses to static exercise in man. J Physiol
359, 365–379.
McCloskey DI & Mitchell JH (1972). Reflex cardiovascular and
respiratory response originating in exercising muscle.
J Physiol 224, 173–186.
McIlveen SA, Hayes SG & Kaufman MP (2001). Both central
command and exercise pressor reflex reset carotid sinus
baroreflex. Am J Physiol 280, H1454–H1463.
Mitchell JH (1990). Neural control of the circulation during
exercise. Med Sci Sports Exerc 22, 141–154.
Mitchell JH, Kaufman MP & Iwamoto GA (1983). The exercise
pressor reflex: its cardiovascular effects, afferent mechanisms,
and central pathways. Ann Rev Physiol 45, 229–242.
Nowak M, Holm S, Biering-Sorensen F, Secher NH & Friberg L
(2005). ‘Central command’ and insular activation during
attempted foot lifting in paraplegic humans. Hum Brain
Mapp 25, 259–265.
Nowak M, Olsen KS, Law I, Holm S, Paulson OB & Secher NH
(1999). Command-related distribution of regional cerebral
blood flow during attempted handgrip. J Appl Physiol 86,
819–824.
Ogoh S, Fisher JP, Dawson EA, White MJ, Secher NH & Raven
PB (2005). Autonomic nervous system influence on arterial
baroreflex control of heart rate during exercise in humans.
J Physiol 566, 599–611.
Ogoh S, Wasmund WL, Keller DM, O-Yurvati A, Gallagher
KM, Mitchell JH & Raven PB (2002). Role of central
command in carotid baroreflex resetting in humans during
static exercise. J Physiol 543, 349–364.
Oppenheimer SM, Gelb A, Girvin JP & Hachinski VC (1992).
Cardiovascular effects of human insular cortex stimulation.
Neurology 42, 1727–1732.
Oppenheimer SM, Kulshreshtha N, Lenz FA, Zhang Z,
Rowland LH & Dougherty PM (1998). Distribution of
cardiovascular related cells within the human thalamus.
Clin Auton Res 8, 173–179.
Potts JT & Mitchell JH (1998). Central interaction between the
carotid baroreflex and the exercise pressor reflex. J Exerc Sci
8, 1–20.
Potts JT, Shi XR & Raven PB (1993). Carotid baroreflex
responsiveness during dynamic exercise in humans. Am J
Physiol 265, H1928–H1938.
Querry RG, Smith SA, Stromstad M, Ide K, Raven PB & Secher
NH (2001). Neural blockade during exercise augments
central command’s contribution to carotid baroreflex
resetting. Am J Physiol 280, H1635–H1644.
Raven PB, Fadel PJ & Smith SA (2002). The influence of central
command on baroreflex resetting during exercise. Exerc
Sport Sci Rev 30, 39–44.
Raven PB, Potts JT & Shi X (1997). Baroreflex regulation of
blood pressure during dynamic exercise. Exerc Sport Sci Rev
25, 365–389.
Ruggiero DA, Mraovitch S, Granata AR, Anwar M & Reis DJ
(1987). A role of insular cortex in cardiovascular function.
J Comp Neurol 257, 189–207.
Downloaded from ep.physoc.org at FMRP/USP on December 13, 2007
Exp Physiol 91.1 pp 51–58
Saper CB (1982). Convergence of autonomic and limbic
connections in the insular cortex of the rat. J Comp Neurol
210, 163–173.
Sheriff DD, O’Leary DS, Scher AM & Rowell LB (1990).
Baroreflex attenuates pressor response to graded muscle
ischemia in exercising dogs. Am J Physiol 258, H305–H310.
Smith JC, Stephens DP, Winchester PK & Williamson JW
(1997). Facial cooling-induced bradycardia: attenuating
effect of central command at exercise onset. Med Sci Sports
Exerc 29, 320–325.
Thornton JM, Aziz T, Schlugman D & Paterson DJ (2002).
Electrical stimulation of the midbrain increases heart rate
and arterial blood pressure in awake humans. J Physiol 539,
615–621.
Thornton JM, Guz A, Murphy K, Griffith AR, Pedersen DL,
Kardos A, Leff A, Adams L, Casadei B & Paterson DJ (2001).
Identification of higher brain centres that may encode the
cardiorespiratory response to exercise in humans. J Physiol
533, 823–836.
Verberne AJ & Owens NC (1998). Cortical modulation of the
cardiovascular system. Prog Neurobiol 54, 149–168.
Waldrop TG, Eldridge FL, Iwamoto GA & Mitchell JH (1996).
Central neural control of respiration and circulation during
exercise. In Handbook of Physiology, chapter 9, section 12,
Exercise: Regulation and Integration of Multiple Systems, ed.
Rowell LB & Shepherd JT, pp. 333–380. American
Physiological Society, Bethesda, MD, USA.
Williamson JW, McColl R & Mathews D (2003). Evidence for
central command activation of the human insular cortex
during exercise. J Appl Physiol 94, 1726–1734.
Williamson JW, McColl R, Mathews D, Ginsburg M & Mitchell
JH (1999). Activation of the insular cortex is affected by the
intensity of exercise. J Appl Physiol 87, 1213–1219.
Williamson JW, McColl R, Mathews D, Mitchell JH, Raven PB
& Morgan WP (2001). Hypnotic manipulation of effort
sense during dynamic exercise: cardiovascular responses and
brain activation. J Appl Physiol 90, 1392–1399.
Williamson JW, McColl R, Mathews D, Mitchell JH, Raven PB
& Morgan WP (2002). Brain activation by central command
during actual and imagined handgrip under hypnosis. J Appl
Physiol 92, 1317–1324.
Yasui Y, Breder CD, Saper CB & Cechetto DF (1991).
Autonomic responses and efferent pathways from the insular
cortex in the rat. J Comp Neur 303, 355–374.
Zhang Z & Oppenheimer SM (1997). Characterization,
distribution and lateralization of baroreceptor-related
neurons in the rat insular cortex. Brain Res 760, 243–250.
Zhang ZH & Oppenheimer SM (2000). Baroreceptive and
somatosensory convergent thalamic neurons project to the
posterior insular cortex in the rat. Brain Res 861, 241–256.
Zuntz N & Geppert J (1886). Über die Natur der normalen
Atemreize und den ort ihrer Wirkung. Arch General Physiol
38, 337–338.
Acknowledgements
J. W. Williamson was supported by an American Heart
Association Grant-in-Aid from the Texas Affiliate, Inc. no.
0050726Y (J.W.W.) and NIH R01 HL59145-04 (J.W.W.).


C 2006 The Authors. Journal compilation

C 2006 The Physiological Society
 New insights into central cardiovascular control during exercise in humans: a
central command update
J. W Williamson, P. J Fadel and J. H Mitchell

Exp Physiol 2006;91;51-58; originally published online Oct 20, 2005;

DOI: 10.1113/expphysiol.2005.032037
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