Table 2.

Summary of the articles used in this review.

Article	Objective	Study sample	Method	Results and Conclusions
Suzuki et al., 20038	Investigate cerebellar and basal ganglia activation during swallowing.	11 right-handed volunteers (24–42 years).	Individuals should swallow the saliva or not, according to verbal commands (“swallow” and “stop”).	Spontaneous swallowing involved the basal ganglia and cerebellum as well as cortical structures.
Martin et al., 20049	Clarify the role of different brain areas in swallowing.	14 right-handed volunteers (mean age of 28 years, standard deviation 6.5).	Participants should perform three different sequences of tasks: (1) saliva swallowing, voluntary elevation of tongue, and voluntary finger opposition; (2) Swallowing saliva, swallowing saliva with effort, and finger opposition; (3) swallowing saliva, voluntary apnea, and finger opposition.	This finding suggests that these areas of the brain may mediate specific processes for swallowing. Approximately 60% of subjects had strong functional lateralization of the postcentral gyrus toward the left hemisphere to swallow, while 40% showed a similar activation trend for the tongue elevation task. This finding supports the view that the oral sensorimotor cortex in the left and right hemispheres are not functionally equivalent.
Mosier et al., 200510	Determine the cortical adaptation mechanisms of swallowing after partial glossectomy (reconstruction with primary closure).	Four patients with partial glossectomy T2 and T3 (mean of 63 years). Eight healthy volunteers (mean 38 years).	Participants had to swallow saliva and water, according to the protocol, after verbal commands.	The adaptive responses involve cortex areas associated with tongue movement planning during swallowing. This reflects adaptive biomechanical processes of tongue movement during swallowing and tongue sensitivity alterations were not verified.
Toogood et al., 200511	Compare brain activation after visual command to swallow and not to swallow.	Eight healthy individuals (mean of 23.8 years, standard deviation of 2.3).	Participants had to swallow their own saliva or not, according to visual stimuli for the commands (“swallow”, “do not swallow”, intercalated with “relax”).	It was concluded that the “swallow” × “do not swallow” paradigm is an effective method to differentiate cortical areas of swallowing processing.
Shibamoto et al., 200712	Elucidate the cortical representations of the oral and pharyngeal stages of swallowing, with different types of food bolus.	21 healthy right-handed adults (mean age of 29.2 years, ranging from 23 to 38).	Participants had to swallow, in the supine position, 5 mL of water at 15 °C, a capsule, and agar (solid) without aid of water and without chewing.	The size of the activated area during the swallowing of water was higher than for agar. The task of swallowing a capsule may require more from oral swallowing and motor coordination than that for solid or liquid food. Cortical representations of swallowing vary by type of food and can explain the responses of variables in the performance of swallowing in patients with oropharyngeal dysphagia.
Martin et al., 200713	Assess the neural representations of voluntary swallowing in healthy elderly.	Nine healthy elderly women (mean 74.2 years, standard deviation 8.1)	Participants had to swallow the saliva accumulated in the mouth or 3 mL of water injected into the oral cavity, in accordance with the visual command.	There was a four-fold increase in the volume of cerebral activation when swallowing water compared to saliva swallowing, particularly the right premotor cortex and the prefrontal cortex. This specific activation pattern may represent a compensatory response to the demands of swallowing water considering the age-related decrease in oral sensorimotor function.
Lowell et al., 200814	Differentiate the motor, sensory planning, and components of motor performance of the cerebral control of swallowing.	14 healthy individuals, only one left-handed (mean age of 36 years, standard deviation of 10.4, ranging from 21 to 52 years).	Four conditions were employed during fMRI: oral sensory stimulation (air pulse), direct swallowing, indirect swallowing, and apnea. During the examination, the individuals were asked to perform tasks after receiving a visual stimulus – symbol: (1) a tube for airflow – oral-sensory stimulation, (2) a lamp – for indirect swallowing, (3) a glass – for direct swallowing and (4) lungs with an X-ray – for apnea.	Sensory oral stimulation and indirect swallowing showed activation in neural areas related to areas activated during spontaneous swallowing. It is suggested that oral sensory stimulation and indirect swallowing have important implications for intervention in swallowing disorders associated with neurological diseases.
Humbert et al., 200915	To assess the functional alterations in swallowing according to age.	11 elderly individuals (mean age of 72.3 years, standard deviation of 7.5, ranging from 64 to 83 years). 12 young individuals (mean age of 27.9 years, standard deviation 4, ranging from 23 to 37 years).	Participants had to swallow saliva, water, and barium, alternating with pauses in swallowing, according to the commands.	The findings suggest that the elderly individuals showed a higher cortical involvement to complete the same swallowing tasks when compared to the younger ones. The elderly showed a higher latency to the onset of pharyngeal swallowing and increased residue of the ingested material in the pharynx. These findings suggest that the elderly had a higher cortical involvement to complete the same swallowing tasks than younger individuals.
Kaway et al., 200916	To investigate brain activation after simultaneous display of stimuli associated with swallowing movements.	12 healthy and right-handed adults, with vision and hearing within the normal range (20–28 years).	Auditory and visual stimuli of the act of swallowing and neck anatomy were presented in association during swallowing. The cortical areas activated with different types of stimuli were analyzed.	According to this study, the audiovisual stimuli associated with the swallowing movement can be applied in the treatment of patients with dysphagia. The activation of areas associated with the swallowing movement (planning and performance) occurred during all stimuli.
Li et al., 200917	To explore the structural and functional changes in patients with amyotrophic lateral sclerosis (ALS), with or without dysphagia, compared to healthy adults.	ALS patients, five with dysphagia and five without dysphagia (32–58 years).	Participants should swallow their own saliva or stop the action, according to visual commands.	During voluntary swallowing of saliva, the preeminent focal activation corresponded to the same cortical area in both groups; however, a decrease in activation was observed in ALS patients with dysphagia
		Ten individuals matched for gender and age to the study group.		Combined, non-invasive neuroimaging techniques may be useful tools for assessing rehabilitation, prognosis, and study strategies for dysphagic patients with ALS, particularly for patients that have ‘negative’ MRI by conventional methods.
Li et al., 200918	To investigate neurorehabilitation mechanisms after dysphagia in patients with unilateral stroke, when compared to healthy adults.	Ten patients after ischemic stroke with severe dysphagia for at least three days (mean age of 70.9 years, standard deviation of 3.4, ranging from 62 to 78 years). Ten healthy elderly individuals (mean age 70.3 years, standard deviation 4.2, ranging from 65 to 75 years).	Participants had to swallow their own saliva or stop the action, according to visual commands.	The results indicate that a unilateral stroke of either cerebral hemisphere may cause dysphagia and recovery of this symptom may be associated with the fact that other unaffected areas start being activated during swallowing.
Malandraki et al., 200919	To identify neural activations of different cerebral components of swallowing in healthy young adults.	Ten healthy young individuals (mean 21.7 years, standard deviation of 2).	Water was injected into the oral cavity of the participants, who should follow random visual commands (“swallow”, “get ready to swallow”, “touch your tongue”, “clear your throat”).	Areas activated during each of the task components showed partial differentiation of neural location for the several components of swallowing. The study was able to identify the brain areas involved in the swallowing task, in agreement with previous findings.
Malandraki et al., 201020	To assess age differences in patterns of neural lateralization during swallowing.	Ten young right-handed individuals (mean age of 21.7 years, standard deviation of 2.1). Nine adults (mean age 70.2 years, standard deviation 3.9)	Water was injected into the oral cavity of the participants, who should follow the commands that appeared on a television at random (“swallow”, “get ready to swallow”, “touch your tongue”, “clear your throat”).	With increasing age, the hemispheric cortical control of swallowing seems to become more symmetrical/bilateral, which may indicate compensatory neural mechanisms of brain aging, commonly seen in other motor and cognitive functions.
Haupage et al., 201021	To correlate CNS adaptation mechanisms with changes in language function.	Six individuals diagnosed with tongue cancer (mean age of 50.8 years – 21–66). Nine healthy individuals (mean age 35.6; 30–48).	The participants were evaluated prior to surgery and after six months through fMRI, with three tasks: “tongue touch”, dry swallowing and water swallowing after auditory command, comparing the inter-individual activation areas (pre and postoperative), preoperative patient with control, and postoperative with control.	Patients who recovered tongue function after partial glossectomy show adaptive responses in the CNS. The increased cortical activation areas after surgery are involved with the planning, the movement and sensation of the tongue during swallowing. Postoperative activation patterns were closer to control levels than to the preoperative exams.
Babaei et al., 201022	To test whether activity of the cortical swallowing network can be increased by sensory stimuli related to food.	14 healthy and right-handed individuals (mean age of 28 years, standard deviation of 10).	The subjects received different visual and olfactory commands to perform saliva or food swallowing (water, lemonade, milk chocolate, and popcorn-flavored solution) at same temperature.	Signal intensity along all sub-cortical regions of the swallowing network significantly increased with stimulation with flavor, when compared with swallowing of saliva and water. The simultaneous olfactory, gustatory, and visual stimulation of ingested substances increases the activity of the swallowing cerebral cortical network. This increase in activity may have implications in the management of dysphagia.
Humbert et al., 201023	To compare the neural activation and the physiology of swallowing in patients with newly diagnosed Alzheimer's disease (AD) and healthy individuals matched for age.	13 Alzheimer patients (mean 74.3 years, standard deviation 8.6, ranging from 58 to 88). 11 healthy individuals (mean age 72.3 years, standard deviation 7.5, ranging from 64 to 83).	Barium and water were injected into the oral cavity of the patients and subjects should swallow when they feel the entire content in their mouth; as well as saliva when they saw the visual command.	The group with AD had significantly lower response in many cortical areas that are traditionally involved in normal swallowing. They did not recruit new regions, or compensate in regions that are normally activated during swallowing. Although swallowing disorders are usually observed in the final stages of AD, changes in the cortical control of swallowing can start long before dysphagia become apparent.
Humbert et al., 201124	To assess brain responses in swallowing tasks, comparing individuals by age and the presence of Alzheimer's disease (AD), through fMRI.	13 elderly individuals with Alzheimer's (mean of 74.3 years, standard deviation 8.6 years – range: 58–88 years). 12 healthy young individuals (mean age 27.9 years, standard deviation 4.0 years – range: 23–37 years) 11 healthy elderly individuals (mean 72.3 years, SD 7.5, range: 58–88 years).	Swallowing of saliva, water, and barium, intercalated with moments of pause in the swallowing task after predetermined commands.	Absence of significant differences in areas of brain activation when comparing elderly individuals, young individuals, and elderly individuals with AD. Individuals with AD required greater effort to perform the pause function during swallowing when the command for this action was requested.
Stice et al., 201125	Compare brain activation during food receiving tasks and receiving monetary reward in young individuals with high and low risk for obesity.	60 young individuals of normal weight, with high and low risk for obesity according to their family members (mean of 15 years, standard deviation 2.9). Of these, 35 had high risk for obesity.	The young individuals were given two stimuli during the examination: (1) stimulus with food reward: after the representation of images – a milkshake or water – received the respective food. This stimulus occurred after a period of fasting to induce hunger; (2) stimulus with monetary reward: during a game, the participant received “money” as a reward (figuratively).	Individuals with high risk for obesity show higher cortical activation when receiving the milkshake, compared to low-risk ones. These young individuals show high responsiveness to circuits connected to reward, in general, with high responsiveness in the somatosensory region connected to food, which can lead to overeating that result in “blunting” of dopamine signaling and high responsiveness to food stimuli.
Malandraki et al., 20112	To determine whether swallowing events recruit different areas of activation, with different amplitudes, comparing young and elderly individuals.	Nine right-handed elderly individuals (mean 70.2 years, standard deviation 3.9). Ten healthy young individuals (mean 21.7 years, standard deviation 2.1).	Water was injected into the oral cavity of the participants, which should follow the commands that appeared on a television at random (“swallow”, “get ready to swallow”, “touch with your tongue”, “clear your throat”).	There was decreased activation in the elderly compared to young individuals during swallowing and the analyzed tasks. These reductions were significant in several primary somatosensory areas, indicating a decline in neural processing of sensory signals to coordinate the swallowing response.
Babaei et al., 201226	To investigate the reproducibility of positive and negative cortical activity (BOLD) related to swallowing in different sessions of fMRI in regions of interest previously demonstrated in other studies.	16 right-handed asymptomatic adult individuals aged 20–34 years, of whom nine were women.	A projection screen was placed in front of the scanner to display visual cues (verbal command) to swallow and/or the image of a cross for ocular fixation between swallows (3s). Two separate sessions were carried out.	All individuals had significant cortical activity within the known areas of the swallowing network in both sessions. The cross-correlation coefficient of the fMRI signal percentage changes and the number of voxels activated through the positive and negative BOLD networks were similar between the two moments. The map of the cortical activity group, as well as length and amplitude of activity induced by spontaneous swallowing in the swallowing cortical network, were reproducible among the studied sessions.
Babaei et al., 201327	To determine the functional connectivity (FC) between brain regions involved in swallowing and characterize the differences in FC between these regions when involved in different tasks (rest or control task).	16 right-handed, adult, asymptomatic individuals aged 20–34 years, of which nine were women.	First the individuals had swallowing analyzed according to a protocol and then, with the aid of a screen for visual projection of commands, three different conditions were assessed: (1) swallowing task after 21 random commands to swallow; (2) ocular fixation on the image of a cross with 21 commands to relax substituting the ocular fixation mark; (3) wakefulness with eyes closed at rest.	Functional connectivity of the swallowing network regions is robust and reproducible across different experimental conditions and is significantly higher during swallowing task when compared to the control of visual task or rest.

SD, standard deviation; fMRI, functional magnetic resonance imaging; AD, Alzheimer's disease; CNS, central nervous system; TV, television; pre-op, preoperative period; post-op, postoperative period; ALS, amyotrophic lateral sclerosis; CVA, cerebrovascular accident.