Functional Brain Imaging of Swallowing: An
Activation Likelihood Estimation Meta-Analysis
Peter So¨ro¨s,1* Yoko Inamoto,1,2 and Ruth E. Martin1
1School of Communication Sciences and Disorders, The University of Western Ontario,
London, Ontario, Canada
2Department of Physical Medicine and Rehabilitation, Johns Hopkins University, Baltimore, Maryland
Abstract: A quantitative, voxel-wise meta-analysis was performed to investigate the cortical control of
water and saliva swallowing. Studies that were included in the meta-analysis (1) examined water swal-
lowing, saliva swallowing, or both, and (2) reported brain activation as coordinates in standard space.
Using these criteria, a systematic literature search identified seven studies that examined water swal-
lowing and five studies of saliva swallowing. An activation likelihood estimation (ALE) meta-analysis
of these studies was performed with GingerALE. For water swallowing, clusters with high activation
likelihood were found in the bilateral sensorimotor cortex, right inferior parietal lobule, and right ante-
rior insula. For saliva swallowing, clusters with high activation likelihood were found in the left senso-
rimotor cortex, right motor cortex, and bilateral cingulate gyrus. A between-condition meta-analysis
revealed clusters with higher activation likelihood for water than for saliva swallowing in the right in-
ferior parietal lobule, right postcentral gyrus, and right anterior insula. Clusters with higher activation
likelihood for saliva than for water swallowing were found in the bilateral supplementary motor area,
bilateral anterior cingulate gyrus, and bilateral precentral gyrus. This meta-analysis emphasizes the
distributed and partly overlapping cortical networks involved in the control of water and saliva swal-
lowing. Water swallowing is associated with right inferior parietal activation, likely reflecting the
sensory processing of intraoral water stimulation. Saliva swallowing more strongly involves premotor
areas, which are crucial for the initiation and control of movements. Hum Brain Mapp 30:2426–2439,
2009. VC 2008 Wiley-Liss, Inc.
Key words: meta-analysis; functional magnetic resonance imaging; positron emission tomography;
magnetoencephalography; swallowing; sensorimotor cortex; premotor cortex; insula; later-
alization
INTRODUCTION
Swallowing is a complex sensorimotor function that is
controlled by cortical, subcortical, and brainstem mecha-
nisms [Miller, 1999] and recruits the coordinated activity
of orofacial, pharyngeal, laryngeal, respiratory, and esoph-
ageal muscles [Doty and Bosma, 1956]. Swallowing com-
prises a voluntary oral preparatory phase during which
ingested material is manipulated within the oral cavity
and moved posteriorly over the tongue surface toward the
pharynx. This is followed by a semi-autonomic pharyngeal
phase in which the airway is closed as the bolus is trans-
ported through the pharynx and into the esophagus
[Dodds et al., 1990].
Contract grant sponsors: Heart and Stroke Foundation of Ontario,
Natural Sciences and Engineering Research Council of Canada,
Ontario Ministry of Health and Long-Term Care Salary Support,
Premier’s Research Excellence Award.
*Correspondence to: Peter So¨ro¨s, Department of Communication
Sciences and Disorders, University of South Carolina, Columbia,
SC 29208, USA. E-mail: peter.soros@gmail.com
Received for publication 22 January 2008; Revised 9 September
2008; Accepted 10 September 2008
DOI: 10.1002/hbm.20680
Published online 23 December 2008 in Wiley InterScience (www.
interscience.wiley.com).
VC 2008 Wiley-Liss, Inc.
r Human Brain Mapping 30:2426–2439 (2009) r

The importance of understanding swallowing neural
control relates in part to the fact that the swallowing motor
sequence is produced by paired muscles, which are organ-
ized about the midline. Little is known about the neural
control of this class of movements because limb move-
ments have formed the basis for most current concepts of
motor control and motor neuroplasticity. However, brain-
mapping studies have suggested that oropharyngeal and
swallowing neural control is distinct from limb motor con-
trol in terms of the extent to which muscles are repre-
sented in both hemispheres [Muellbacher et al., 1999], as
well as the neuroplastic effects of central injury [Hamdy
et al., 1998; Mistry et al., 2007]. Thus, an understanding of
the neural basis of swallowing is important in terms of ba-
sic neuroscience. Swallowing neural control is also impor-
tant from a clinical perspective because injury to the cen-
tral nervous system frequently results in significant swal-
lowing impairment [Logemann, 1996]. Indeed, brain injury
can give rise to severe and protracted swallowing prob-
lems, which necessitate tube feeding. Current understand-
ing of the neuropathophysiology of swallowing impair-
ment, the neuroplastic mechanisms underlying swallowing
recovery, as well as the principles of swallowing rehabili-
tation is limited [for review, see Martin, 2008].
Functional brain imaging has greatly advanced our
understanding of the neural basis of swallowing. In
humans, functional imaging substantiated the crucial role
of the cerebral cortex for the control of voluntary and auto-
matic swallowing [Hamdy et al., 1999a,b; Kern et al.,
2001b; Martin et al., 2001, 2004, 2007; Mosier et al., 1999a,b;
Zald and Pardo, 1999], corroborating earlier findings
obtained by electrophysiologic techniques in awake prima-
tes [Martin and Sessle, 1993; Martin et al., 1997, 1999; Nar-
ita et al., 1999; Yao et al., 2002]. However, the exact neuro-
anatomy and functional significance of swallowing-related
networks in humans are not entirely clear. Although some
cortical swallowing foci have consistently been identified,
discrepancies have also emerged. For example, some stud-
ies have reported lateralization of sensorimotor cortical
activation for swallowing [Dziewas et al., 2003; Martin
et al., 2004; Teismann et al., 2008], whereas others have
identified more bilateral activation [Hamdy et al., 1999b;
Zald and Pardo, 1999]. Similarly, swallow-related activa-
tion of the insula has varied with respect to the left
[Dziewas et al., 2003] and right [Martin et al., 2001] hemi-
sphere and anterior [Hamdy et al., 1999a] versus posterior
[Suzuki et al., 2003] insular location.
These discrepancies may reflect methodological variation
across studies. Functional magnetic resonance imaging
(fMRI), positron emission tomography (PET), and magne-
toencephalography (MEG), the imaging techniques most
frequently used to investigate the neural basis of swallow-
ing, represent different aspects of brain activity. fMRI
detects local task-related changes in cerebral blood oxygen-
ation, closely reflecting the underlying neural activity
[Logothetis et al., 2001]. PET uses radioactive tracers to
study local changes of neurophysiological parameters,
such as brain perfusion (H2O PET) and glucose metabo-
lism (18F-fluorodeoxyglucose PET). MEG, finally, measures
the small magnetic field changes corresponding to electri-
cal brain activity. Each of these imaging modalities
presents inherent challenges for swallowing research.
Functional imaging of swallowing using fMRI is challeng-
ing because of the potential artifacts associated with swal-
lowing-related head movement and magnetic susceptibility
phenomena due to movements outside the field of view
(in particular movements of the jaw and the tongue) [Birn
et al., 1998]. MEG of swallowing-related brain activity may
be affected by myo-electric discharges, which are consider-
ably larger than the magnetic brain activity under investi-
gation [Loose et al., 2001; So¨ro¨s et al., 2003].
Functional imaging studies of swallowing are also heter-
ogenous in terms of the swallowing tasks studied (volun-
tary or reflexive water swallowing; voluntary or naı¨ve
saliva swallowing), and the demographics of the partici-
pants. Even within tasks, experimental designs have dif-
fered between studies regarding the frequency and the
total number of swallows, and, for water swallowing,
bolus delivery methods and bolus volume, and block ver-
sus single event-related imaging paradigm, all of which
are potential confounding variables in individual studies.
Given the potential bias introduced by these discrepant
methodologies, it would be advantageous to identify swal-
lowing-related brain activity that is common across studies
and thus relatively less affected by distinct experimental
designs. Meta-analysis is a statistical integration approach
that examines the concordance of results across a corpus
of studies and extracts the most significant finding [Egger
and Smith, 1997]. Brain-imaging studies are well suited to
meta-analysis because their findings are typically reported
in standard stereotaxic coordinates.
This study employed a novel meta-analysis technique
based on activation likelihood estimation (ALE) [Chein
et al., 2002; Turkeltaub et al., 2002]. ALE is a quantitative
voxel-wise meta-analysis technique that pools the results
of several studies, expressed by the standard space coordi-
nates of activation maxima, estimates the activation likeli-
hood in a given voxel, and rigorously tests the significance
of the ALE statistic [Laird et al., 2005a]. ALE has been
successfully used for meta-analyses of imaging data from
different neurofunctional systems and cognitive domains
[e.g., Brown et al., 2005; Price et al., 2005].
The aim of this meta-analysis of swallowing-related
brain activity was to identify and compare brain activation
associated with two behaviorally distinct swallowing
tasks, voluntary water swallowing and voluntary saliva
swallowing.
MATERIALS AND METHODS
Search Strategies
To identify functional brain imaging studies on swallow-
ing, literature searches were performed using four differ-
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