Dysphagia (2010) 25:250–257
DOI 10.1007/s00455-009-9249-5
REVIEW ARTICLE
Supranuclear Control of Swallowing
Norman A. Leopold Æ Stephanie K. Daniels
Received: 9 June 2009 / Accepted: 13 August 2009 / Published online: 3 September 2009
 Springer Science+Business Media, LLC 2009
Abstract Swallowing is an act requiring complex sen-
sorimotor integration. Using a variety of methods first used
to study limb physiology, initial efforts to study swallow-
ing have yielded information that multiple cortical and
subcortical regions are active participants. Not surpris-
ingly, the regions activated appear to overlap those
involved in both oral and nonoral motor behaviors. This
review offers a perspective that considers the supranuclear
control of swallowing in light of these physiological
similarities.
Keywords Ingestion
Swallowing
Supranuclear

Motor control
fMRI
Feedforward
Anticipation

Lateralization
Basal ganglia
Deglutition

Deglutition disorders
Swallowing begins early in utero [1]. Despite its primitive
origins, the swallow is one of the last motor functions to
undergo rigorous scientific scrutiny. However, the supra-
nuclear control of the complex event of swallowing is
likely to be similar to other movements [2, 3], with regional
N. A. Leopold
Department of Medicine, Division of Neurology,
Crozer-Chester Medical Center, Upland, PA 19013, USA
S. K. Daniels
Michael E. DeBakey VA Medical Center,
Department of Physical Medicine and Rehabilitation,
Baylor College of Medicine, Houston, TX 77030, USA
N. A. Leopold (&)
Parkinson Disease and Movement Disorder Center,
Lewis House, Upland, PA 19013, USA
e-mail: norman.leopold@crozer.org
123
differences subserving anticipatory, preparatory, and
executory functions.
Whether self-initiated or externally triggered, all
movements are a response to one or a variety of extero-
ceptive, interoceptive, affective, or cognitive stimuli
(Fig. 1). The governance of anticipatory and preparatory
movement components is processed by an expansive net-
work of bidirectional and interconnected cortical regions
and their subcortical nuclear counterparts [4]. However,
unlike other movements, a successful swallow must
include, indeed concludes, with a reflex stage. The supra-
nuclear (defined here as structures above the brainstem)
sensory afferents and motor efferents for swallowing con-
verge onto the central pattern generator (CPG) of dorso-
lateral medulla [5]. Neuronal aggregates interposed
between the cortex and hindbrain also integrate the asso-
ciated movements of swallowing, including lip pursing,
jaw closure, and respiratory cessation.
Motor Control: A Comparison
The first component of the swallow, the last stage of bolus
movement under voluntary control, begins typically with
respiratory cessation and synergistic contractions of mul-
tiple oral and perioral muscles. Therefore, it is instructive
to apply the knowledge of motor control over these other
cranial muscles and diaphragm to appreciate the complex
origins of oral behaviors coalescing in the oral stage of the
swallow. By example, the neural organization of facial
movement has been examined in detail using a variety of
techniques. The classical teaching of Hughlings Jackson
proposes that decussating fibers arising from the primary
motor cortex (M1) govern contraction of the contralateral
lower facial muscles in a manner similar to that of the
N. A. Leopold, S. K. Daniels: Supranuclear Control of Swallowing
Fig. 1 A schematic diagram incorporating feedforward sensory
systems and executive motor outputs resulting in a swallow. A,
amygdala; I, insula; OFC, orbitofrontal cortex; D, dorsolateral
prefrontal motor cortex; Pre-SMA, presupplementary area; SMA,
supplementary area; C, cingulate cortex; NTS, nucleus tractus
limbs [6]. Control of upper face and those muscles acti-
vated more during emotional expression reside in other
cortical areas.
Knowledge of facial movement control has been greatly
expanded by contemporary nonhuman primate research [7]
so as to implicate at least five facial cortical motor regions
interconnected via corticocortical fibers: the primary motor
cortex (M1), the supplementary motor (M2), the rostral
cingulate (M3), the dorsal cingulate (M4), and the ventral
lateral premotor (LPMCv) cortices. Each motor region
synapses directly on the facial nucleus: M1 and LPMCv
project primarily contralaterally; M2–M4 distribute their
projections more symmetrically.
Reflecting the organization of M1, the M2–M4 and
LPMCv face regions are somatopically organized.
Although cortical innervation of trigeminal, lingual, and
diaphragm motor nuclei beyond the boundaries of M1 has
received less attention, functional magnetic resonance
imaging (fMRI) studies of volitional tongue movements
document M2 involvement plus operculum, insula, thala-
mus, and cerebellum [8, 9]. Similar regional activation also
occurs with volitional diaphragmatic efforts [10, 11].
Acknowledging participation of perioral muscles in the
earliest phase of the swallow, Kern et al. [12] concluded
that control of isolated but swallow-related movements
could not be segregated from those regions activated dur-
ing a swallow. Using movement-related cortical potentials
(MRCP), Satow et al. [13] also found no significant ana-
tomic differences between swallow and isolated voluntary
tongue movements. They noted that MRCPs were earlier
251
solitarius; NA, nucleus ambiguus; DMN, dorsal motor nucleus of
vagus. Adapted with permission from Dysphagia following stroke by
S. K. Daniels and M. L Huckabee. Copyright 2008 Plural
Publishing, Inc. All rights reserved
for the swallow than for tongue movements, but they did
not entertain that this result may have been due to other
oral muscle activity such as jaw and lip closure that pre-
cede the swallow. Human tongue movements without a
subsequent swallow activate primary sensorimotor (S1/
M1) and M2 areas bilaterally and dorsal prefrontal, infe-
rior, and superior parietal cortices [9, 14, 15]. Tongue
movement decoupled from a swallow also activates the
putamen and thalamus [15, 16].
Ingestion: Oral-Stage Anatomy
Once oral transfer begins, multiple cortical and subcortical
regions of activation have been recorded using fMRI [12,
17–22], positron emission tomography (PET) [23–25], and
MRCP [26–30]. Of these, fMRI provides the most acces-
sible noninvasive procedure to accurately identify func-
tional anatomic networks (see [31] for a review of fMRI
benefits and limitations). Although its spatial resolution is
excellent, temporal resolution limitations do not allow the
sequencing of the complex swallow-related neuronal
events. The regions activated hinge on the study paradigm
such as automatic versus a triggered swallow, degree of
required subject attention, saliva versus a water bolus
swallow, the volume and chemosensory bolus characteris-
tics of the bolus, and whether swallows followed a block-
trial or single-trial technique. Common areas of activation
in nearly all reports include M1–M4, frontal operculum,
insula, and S1–S2. Other cortical regions noted less
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consistently are the parietal association cortex; lingual,
fusiform, and hippocampal gyri; cuneus; precuneus; and
cerebellum [3, 9, 12, 15, 16, 19, 23, 25, 27, 31–34]. Not
only does the anatomy of the response vary with the par-
adigm but also the intensity: the greater the stimulus, the
larger the cortical activation magnitude. Martin et al. [31]
reported that the volume of cortical activation was four
times greater with water than with saliva bolus, a possible
reflection of both volume and other sensory feedforward
information. However, this may be age-dependent.
Increased activity following saliva swallows versus water
or even barium was recorded in the cortical swallowing
area in older subjects [35].
Oral Preparatory-Stage-Related Cortical Activation
Bolus oral transfer is preceded by an oral preparatory stage
that is highly dependent on cortical sensorimotor integra-
tion. Bolus-related touch, temperature, taste, texture, and
viscosity stimulate an expansive cortical sensory field
which includes the insula, amygdala, and orbitofrontal
cortex (OFC) [36, 37]. Oral somatosensory stimulation also
activates S1, S2, and the parietal association cortex. Con-
versely, oropharyngeal anesthesia blunts S1 and M1
responses to oral stimuli [38].
At least in the S1, fMRI has identified somatotopic
sensory organization of teeth, tongue, and lips, all struc-
tures actively involved in bolus preparation [39]. These
oral-based stimuli inform the OFC which then is likely to
exert at least a permissive roll in swallow initiation during
normal meals, a function likely to be obviated during
command-dependent research paradigms.
Sensory bolus characteristics also drive the three phases
of mastication, including food preparation, chewing, and
preswallow bolus formation and positioning. In nonhuman
primates, anatomical investigations of projections to the
corticomasticatory area (CMA) by Hatanaka et al. [40]
identified input from S1 and other sensory areas, M2, M3,
the ventral premotor cortex. In turn, the CMA projected to
the putamen, lateral brainstem reticular formation, tri-
geminal sensory nuclei, and the contralateral medial
parabranchial and Kolliker-Fuse nuclei. In sheep, stimu-
lation of the chewing area of the fronto-orbital cortex
inhibits motoneurons in the medullary swallowing CPG
[41]. In humans, fMRI during mastication activates oro-
facial sensorimotor and premotor cortex and both the
posterior parietal and prefrontal cortical areas [42]. Con-
versely, by cooling and thereby inhibiting this region,
Narita et al. [43] were able to markedly suppress all
mastication phases without adversely affecting swallow
duration.
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N. A. Leopold, S. K. Daniels: Supranuclear Control of Swallowing
Is There an Anticipatory Cortically Dependent Stage
of Ingestion?
Anticipation in Normal Human Behavior
Anticipation as a prelude to motor preparation is critical for
organizing motor performance, successful learning, and
adaptation. It is stimulus- not response-dependent. An
anticipatory stage has been demonstrated for gait, hand,
and eye movements [44–47] as well as for nonmotor
responses of pain and emotion [48–50]. By example,
anticipation activates the rostral anterior cingulate and
dorsolateral prefrontal cortices, parietal regions, and more
medial sectors of the OFC, while negative cognitive
anticipation (distraction) can downregulate the medial
prefrontal cortex and amygdala [51]. Limb motor control
incorporates feedforward sensory information from the
posterior parietal cortex and cerebellum to direct motor
planning and execution [52–54].
Evidence for a Swallow-Related Anticipatory Stage
External or internal stimuli that anticipate the introduction
of food into the mouth and all intraoral stimuli have
feedforward attributes that likely modify the oral or sub-
sequent stages of a swallow. An anticipatory stage of
ingestion has been proposed [55] but there have been few
studies that directly address this concept [56]. However,
almost 100 years ago Pavlov described what has been
labeled the cephalic phase of digestion when he observed
that ‘‘…the observation and contemplation of food, must be
accepted as an undoubted excitant of the nervous center for
the salivary gland’’ [57]. Although the thrust of this line of
study was to identify and confirm the earliest stage of food
digestion, saliva also is critical in food lubrication and is
therefore an integral part of bolus preparation prior to a
swallow.
Identifying an association between externally presented
food-related stimuli and increased activity in structures of
the swallowing medullary CPG implies but does not confer
that swallow parameters will be altered. However, Maeda
et al. [56], measuring swallow latency in subjects shown
either photographs intended to induce drinking or neutral
stimuli, found reduced swallow latency of water after only
presentation of drink-related visual stimuli. Although fMRI
was not included in their study, St-Onge et al. [58] dem-
onstrated that visual and tactile food but not nonfood
stimuli activate the insula and other synaptically related
cortices, including the superior temporal, parahippocampal,
and hippocampal gyri. Even subliminal stimuli can activate
the swallow-related cortical region, including the cingulate,
prefrontal, insula, and sensory/motor regions [59].
N. A. Leopold, S. K. Daniels: Supranuclear Control of Swallowing
In addition to stimulating the primary and associative
sensory cortical regions, food-related visual and olfactory
stimuli excite other cortical regions, including anterior
cingulate, insula, and amygdala cortices, to gain access
either directly or indirectly to the dorsal motor nucleus of
the vagus and nucleus solitarius [60]. The amygdala is of
special interest in that within portions of its subnuclei, a
previous neutral stimulus can be transformed into a con-
ditional stimulus. Once established, anticipation of the
conditional stimulus can provoke a fear response that may
include selective or generalized behavioral immobility
[61]. This may be the neuroanatomic substrate for the fear-
related swallow inhibition or phagophobia.
Is There Hemispheric Symmetry Controlling
Swallowing?
Physiologic Studies of Swallow-Related Hemispheric
Symmetry
Prepharyngeal stages of swallowing are commanded by
bilateral cortical regions, although the degree of hemi-
spheric symmetry is in question [12, 15, 17, 19, 43].
Although the number of subjects studied to date is rela-
tively small, attempts to lateralize at least the execution of
the swallow have produced inconclusive results. Initial
reports found no consistent hemispheric preference for
swallowing [12, 19, 21, 24]. Subsequent studies supported
preferential left hemispheric activation with swallowing.
Furthermore, in studies asserting lateralization, the results
cannot be negated by technical considerations as similar
results were found using fMRI [15, 31], PET [25], and
magnetoencephalography [26]. Martin et al. [15] also
observed that isolated tongue elevation tended to lateralize
to the left hemisphere. Although detecting no significant
motor hemispheric preference with a variety of tongue
movements, Watanabe et al. [30] reported that the left
parietal lobe tended to be more activated than the right.
They posited that because the left hemisphere dominates
language, other lingual functions, including those associ-
ated with deglutition, might be so inclined. Support for this
proposition might be found in a study by Hauk et al. [62].
Using event-related fMRI while passively reading an
action word such as ‘‘licking’’ preferentially activated the
left premotor cortex that was in direct proximity with areas
activated by volitional tongue movements.
Another way to study lateralization is with a dual-task
paradigm. This paradigm indirectly evaluates lateralized
cortical systems by comparing performance on tasks at
baseline and with a concurrent or competitive condition
[63, 64]. Swallowing was measured at baseline and during
three concurrent tasks: finger-tapping (left and right hands),
253
line orientation, and silent word repetition. Right and left
cerebral hemisphere contributions to swallowing were
identified. Silent repetition, which primarily activates the
left hemisphere, and line orientation, a visuospatial process
which primarily activates the right hemisphere, interfered
with swallowing behavior when performed concurrently.
Both right- and left-hand finger-tapping, which selectively
activates the left and right sensorimotor cortex, respec-
tively, also interfered with swallowing. Results on swal-
lowing behavior differed in each of the cognitive tasks.
Silent repetition yielded a significant change in the volume
per swallows, while line orientation negatively impacted
the number of swallows. These findings suggest perhaps a
more complex nature of swallowing lateralization, with
two hemispheres having asymmetrical roles in swallowing
behavior.
Hemispheric Symmetry of Swallowing in Ablation
Paradigms
In humans, the importance of supranuclear regions in
swallowing has also been identified in ablation paradigms,
which utilize computed tomography or MRI of focal
lesions in acute stroke patients. Studies have identified
that unilateral infarctions of either cerebral hemisphere
can produce dysphagia. Two competing hypotheses have
been advanced: lateralization of function and bilateral
representation of swallowing. Initial studies demonstrated
that swallowing behaviors may differ following left
hemispheric damage (LHD) and right hemispheric damage
(RHD); LHD was associated with oral-stage dysfunction
while RHD was associated with pharyngeal-stage dys-
function and aspiration [65, 66]. Moreover, it has been
suggested that RHD is associated with more protracted
dysphagia [67]. Other studies of stroke patients found that
lesion site rather than hemisphere or lesion size predicted
dysphagia characteristics or aspiration risk [68–70]. Spe-
cifically, anterior locations and subcortical periventricular
white matter (PVWM) sites were commonly infarcted in
patients with risk of aspiration, whereas patients without
risk of aspiration were more likely to have posterior
lesions or lesions to subcortical gray matter structures.
Ischemic infarction of the insula has also been associated
with dysphagia [71, 72]. Robbins et al. [65] found an
interaction between anterior-posterior location and lesion
size. Anterior lesions were significantly larger and were
associated with more severe dysphagia than posterior
lesions. Specific sites that are associated with dysphagia
include the anterior insula, premotor cortex, and the
PVWM [68]. It is unclear whether specific lesion locations
or large-size lesions are associated with persistent dys-
phagia and risk of aspiration in chronic post-stroke
patients.
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The data, both physiologic and clinical, support asym-
metric hemispheric control of swallowing. However, the
degree of asymmetry for a given task assigned to each
hemisphere has not been explored.
How Does Basal Ganglia Physiology and Pathology
Influence Swallowing?
Lateralized hemispheric input directing swallows or other
willed movements does not solely inform brainstem or
spinal motor systems because all voluntary motor programs
are nearly futile without basal ganglia input. A number of
proposed partially closed and functionally related loops
have been identified that link the basal ganglia and related
thalamic nuclei with sensorimotor, supplementary motor,
premotor, associative, and limbic cortices [4, 73, 74]. Many
of these circuits operate in parallel yet function in a seg-
regated fashion [69]. Their somatotopic organization sup-
ports a variety of motor- and cognitively related functions,
including the selection, preparation, and execution of a
motor program, sensorimotor integration, and motor
learning [75]. By example, interconnections with prefrontal
regions modify volitional movement and those with M2–
M4 automatic movements. Program selection (motor
planning), preparation, and execution are associated with
activation of the caudate nucleus, rostral putamen, and
posterior putamen, respectively [76]. The caudate receives
and projects to the prefrontal cortex, the anterior putamen
to the premotor cortex, and the posterior putamen to M1
[77, 78]. Premotor areas critical to the preparatory aspect of
movement, including pre-SMA and SMA, connect via the
anterior putamen/ventrolateral thalamic nucleus to generate
movements that arise primarily from internal rather than
external cues [79].
Basal Ganglia Influence over Oral Motor: Animal
Studies
Animal studies designed to study basal ganglia influences
on oral motor functions are few. Masseter and digastric
muscle-related jaw movements can be elicited by dopa-
minergic and cholinergic stimulation of several basal
ganglia regions, including the striatum and substantia nigra
zona reticulata (SNZR), a major efferent source of basal
ganglia processing [80]. Orofaciolingual movements can
be evoked by microstimulation and GABA microinjection
of the SNZR in decorticate rats [81]. In nonhuman pri-
mates, systemic injections of the nigral neurotoxin 1-
methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cause
a levodopa-responsive parkinsonism, including markedly
reduced swallowing [82].
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N. A. Leopold, S. K. Daniels: Supranuclear Control of Swallowing
Basal Ganglia Influence over Oral Motor: Normal
Human Studies
Documentation of basal ganglia activation in human studies
of swallowing is supportive, but again the literature is sparse.
Using fMRI, Martin et al. [83] noted putaminal activation
with an instructed rather than a ‘‘naı̈ve’’ swallow. Hamdy
et al. [16] found putamen and caudate activation during water
oral infusion, although cortical activation was much more
consistent. Other fMRI studies have observed increased
swallow-induced regional activity in the putamen, globus
pallidus, and substantia nigra [18, 22]. PET also identified
swallow-related increased blood flow in the putamen [22].
Intimate connections with the pontine and medullary reticular
formations [84, 85] inject basal ganglia influences into the
repertoire of nonreflexive motor activities, preprogrammed to
foster species survival such as locomotion, mastication, and
respiration [10, 86]. Therefore, it is unlikely that the findings
to date are an accurate reflection of basal ganglia participation
in swallowing. Indeed, one might look only to the clinical
setting for confirmation.
Basal Ganglia Influence over Oral Motor: Disease
States
Parkinson’s disease (PD), the prototypic basal ganglia
disease, is an illness characterized by bradykinesia, rigid-
ity, postural instability and rest tremor. Although impair-
ments in each of the stages of ingestion are reported in PD
[87], the most relevant of ingestion-related consequences
of impaired basal ganglia-thalamic-supplementary cortical
circuitry are those affecting its most voluntary aspects of
swallowing: its oral preparatory and oral stages. Impaired
spontaneous, self-generated midline bulbar functions are
often early disease manifestations. Characteristic findings
are diminished facial and vocal expressivity (hypomimia
and hypophonia, respectively), reduced blink rate, and
sialorrhea, in part due to infrequent spontaneous swallow-
ing. Oral-preparatory and oral-stage abnormalities include
slow oral acceptance of the bolus, poor bolus formation,
reduced bolus oral manipulation, inadequate or dysfunc-
tional mastication, and difficulties initiating the swallow,
including segmented or ‘‘piecemeal’’ bolus swallowing and
lingual pumping [87].
Dysphagia is also symptomatic of other parkinsonian
syndromes, including drug-induced parkinsonism [88] and
degenerative basal ganglia illnesses, including progressive
supranuclear palsy (PSP), multiple-system atrophy, and
Huntington’s disease (HD) [89, 90]. Swallow aberrations
involving oral preparatory and oral stages are in part sim-
ilar to those of PD. However, both PSP and HD are
somewhat atypical in that relative and absolute
N. A. Leopold, S. K. Daniels: Supranuclear Control of Swallowing
tachyphagia, respectively, have been reported [89, 90].
Tachyphagia, in an otherwise normal-swallowing subject,
may not cause dysphagic symptoms; in PSP and HD
patients, it enhances aspiration risk.
Summary
Simple limb movements are the final expressions arising
from interactions between multiple cortical and basal
ganglia regions, aggregated into neural networks in
response to feedforward and feedback stimuli. Even simple
repetitive self-induced or externally triggered finger-tap-
ping engages frontal premotor regions, parietal regions,
insula, contralateral anterior putamen, and midbrain [91].
Complex motor events such as swallowing recruit more
extensive networks, but regional differences between limb
movements and swallowing are likely to be minor.
From results derived from fMRI studies of swallowing, it
might be concluded that nearly all cortical and subcortical
gray region structures are activated during one of several
prepharyngeal phases of ingestion. Depending on the con-
text of each investigation, that conclusion may in fact be
correct. However, a meta-analysis of multiple studies of
water or saliva swallows concluded that activation was
primarily in the right hemisphere for water (S1, S2, and
insula) and bilateral for saliva (M1, M2, and M3). Isolating
the importance of these regions unintentionally diminishes
the potential influence of other supratentorial regions. The
absence of statistical activation should not be interpreted as
regional noninvolvement. Furthermore, if taste, texture, pH,
and/or thermal oral stimuli were methodological inclusions,
regional activation would very likely change.
A fuller understanding of the swallow will come as
existing technologies evolve and newer technologies
emerge for evaluating neural connectivity. This will allow
exploration of other questions, including how feedforward
sensory modeling directs motor expression of the swallow,
how cognitive and affective aspects of procedural para-
digms alter their results, how swallowing is affected by
multitasking in those with the supratentorial neurologic
diseases, how complex oral stimuli modify swallow-related
cortical activity, and what other supratentorial-brainstem
pathways might be involved in swallowing?
Acknowledgments The authors acknowledge Maggie-Lee Hucka-
bee, PhD, whose efforts were the major stimulus for this review.
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