The Role of the Insular Cortex in Dysphagia

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1 Dysphagia 12: (1997) Springer-Verlag New York Inc The Role of the Insular Cortex in Dysphagia Stephanie K. Daniels, MS, CCC 1 and Anne L. Foundas, MD 2 1 Audiology/Speech Pathology Service, 2 Neurology Service, Veteran s Affairs Medical Center, New Orleans, Louisiana, USA and 1,2 Department of Psychiatry and Neurology, Tulane University School of Medicine, New Orleans, Louisiana, USA Abstract. Recent data indicate that dysphagia may occur following unilateral cortical stroke; however, the elucidation of specific cytoarchitectonic sites that produce deglutition disorders remains unclear. In a previous study of unilateral cortical stroke patients with dysphagia, Daniels et al. [8] proposed that the insula may be important in swallowing as it was the most common lesion site in the patients studied. Therefore, 4 unilateral stroke patients with discrete lesions of the insular cortex were studied to further facilitate understanding of the role of the insula in swallowing. Dysphagia, as confirmed by videofluoroscopy, was evident in 3 of the 4 patients; all had lesions that involved the anterior insula, whereas the only patient without dysphagia had a lesion restricted to the posterior insula. These data suggest that the anterior insula may be an important cortical substrate in swallowing. The anterior insula has connections to the primary and supplementary motor cortices, the ventroposterior medial nucleus of the thalamus, and to the nucleus tractus solitarius, all of which are important regions in the mediation of oropharyngeal swallowing. Therefore, discrete lesions of the anterior insula may disrupt these connections and, thereby, produce dysphagia. Key words: Stroke Insula Videofluoroscopy Deglutition Deglutition disorders. Correspondence to: Stephanie K. Daniels, M.S., CCC, Speech Pathology Service (126), VA Medical Center, 1601 Perdido Street, New Orleans, LA 70146, USA Traditionally, dysphagia has been associated with brainstem or bilateral cortical lesions [1], and deglutition disorders resulting from these lesions have been well documented [2 7]. Although recent studies have demonstrated that dysphagia may also occur following unilateral cortical stroke [1,8 16], the specific cortical lesions that may produce dysphagia remain unknown [8 10,16 19]. To date, most studies of unilateral stroke and dysphagia have focused upon differences in patterns of dysphagia in left vs. right hemispheric stroke [9,10,16 19]. To our knowledge, only one study attempted to document the precise neuroanatomical location of strokes that produce dysphagia [8]. In that study, Daniels et al. [8] studied dysphagia following unilateral stroke in 8 patients with left hemispheric damage (LHD) and 8 with right hemispheric damage (RHD). The insular cortex was the most common site of involvement, as it was lesioned in 11 of the 16 unilateral stroke patients with dysphagia. This finding was unexpected as lesions to the insula had not previously been associated with dysphagia. Therefore, Daniels et al. postulated that the insula may be important in swallowing because of its connectivity to crucial cortical, subcortical, and brainstem sites known to be important in swallowing. As the insula has been associated with related swallowing and nutritional properties such as coordinated interaction of oral musculature, gustation, and autonomic functions, through connectivity or inherent properties of its own [20 27], it was hypothesized that the insula, particularly the anterior insula, may contribute to oral and pharyngeal motility. To further elucidate the possible role of the insula in deglutition, 4 cases of unilateral stroke patients with discrete lesions of the insula were investigated. Neuroimaging studies, neurological examination, videofluoroscopy, bedside swallowing evaluation, and clinical oropharyngeal examination were performed on all patients. The clinical findings and the extent of the insular lesions in these 4 patients demonstrate the probable importance of the anterior insula in the mediation of swallowing. Subjects and Methods Subjects were selected from a sample of patients (n 39) enrolled in a prospective dysphagia study consisting of consecutive unilateral

2 S.K. Daniels and A.L. Foundas: Insular Cortex in Dysphagia 147 stroke patients with new neurological deficits admitted to the Veterans Affairs Medical Center in New Orleans. The participants had no prior history of dysphagia, dementia, or neurodegenerative disorders. They consisted of 4 males, ages years (mean age 55.5 years) who had sustained a unilateral cortical stroke with the lesion isolated to the insular cortex, as documented on computed tomography (CT) scan of the head. Four additional patients in the larger stroke sample had lesions that included portions of the insula and adjacent cortical regions. Three of these 4 had dysphagia. However, given that the lesions in these additional 4 patients extended beyond the insular cortex, they were not included in further analysis. Procedures A neurological examination was completed upon hospital admission. Speech-language testing, oromotor examination, and bedside swallowing assessment were conducted within the first week of hospitalization, except for Case 2, who was referred for evaluation 4 months after the stroke. Each patient underwent a CT scan and videofluoroscopic swallow study (VSS) within 1 week of stroke onset, except for Case 2 who underwent the VSS 4 months after the stroke. Neurological Examination The neurological evaluation included mental status examination and an elemental neurological assessment (Appendix 1). The mental status examination included tests of memory, intention, attention, language and related functions, neglect, and visuospatial abilities. The elemental neurological assessment included cranial nerve examination, sensory (pain, temperature, proprioception, and vibration), motor (bulk, tone, strength, movement disorders), cerebellar, gait and station, deep tendon reflexes, and pathological reflexes (Babinski response and frontal release signs). Speech-Language Assessment Speech assessment included evaluation of articulatory precision and agility, fluency, resonance, and intelligibility. Language assessment consisted of evaluation of auditory comprehension, verbal fluency, naming, repetition, reading comprehension, and writing. Standardized testing in all areas was completed, as warranted, and consisted of the Western Aphasia Battery [28] and the Boston Naming Test [29]. Oromotor Examination Assessment of oral musculature symmetry, strength, agility and sensation was completed (Appendix 2). Features of the oromotor examination included measurements of isolated movement as well as continual speech and nonspeech movements of the mandible, lips, tongue, velum, and larynx. Light touch of the face was examined as well as the presence of gag and volitional cough. Identification of dysphonic voice quality was made and classified as wet-hoarseness, strained, breathy, or nonspecific hoarseness. Bedside Swallowing Examination The clinical swallowing assessment consisted of administration of liquid, semisolid, and solid consistencies at varying calibrated volumes with assessment of oral transition, oral retention, initiation of laryngeal elevation, laryngeal excursion, voice quality after swallow, and spontaneous cough. Assessments were initiated with a 3-ml liquid bolus and progressed with increasing volumes as tolerated by the patient. Semisolid and solid volumes were initiated at half teaspoon volumes and progressed to continuous ingestion. Administration of a consistency was terminated if a patient demonstrated, on two swallows, either a cough or voice changes after the swallow. Fluoroscopic Examination The VSS was performed by speech pathology in conjunction with radiology. VSS samples were recorded using a Super-VHS videocassette recorder which was coupled to a counter timer that encoded digital time in hundredths of a second on each video frame. A video recording of the oral cavity (anterior to the lips) and the pharynx (inferior to the upper esophageal sphincter) was obtained in the lateral plane, as the patient swallowed liquid barium at volumes of 3, 5, 10, and 20 ml, and 1 2 teaspoon barium paste, twice each. Eight features of oropharyngeal dysmotility were evaluated. In the oral stage these features were anterior bolus loss, delayed initiation of movement, and uncoordinated initiation of oral transfer. Anterior bolus loss was identified as spillage from the lips. Delayed initiation of movement was identified as inability to begin oral transfer upon command to swallow. Uncoordinated initiation of oral transfer was defined as groping and effortful labial, lingual, and mandibular movements. The pharyngeal stage dysmotility patterns evaluated were delayed pharyngeal swallow, reduced laryngeal excursion, penetration into the laryngeal vestibule, aspiration, and stasis. Delayed pharyngeal swallow was measured from the time the bolus head reached the point where the ramus of the mandible bisects the base of the tongue until the onset of laryngeal excursion [30]. The delay was rated as mild ( sec delay), moderate (3 5 sec delay), and severe (6 sec or greater delay). Patients with delay times <0.45 sec were considered within normal limits, a designation consistent with Tracy et al. [31] who identified average delay time for normal controls under age 60 as 0.24 sec, and 0.36 sec for those over age 60. Vallecular and hypopharyngeal locations of the bolus prior to elicitation of the pharyngeal swallow were identified as pooling. Decreased laryngeal elevation was identified as reduced anterior, superior hylolaryngeal excursion. Stasis was identified as pharyngeal residue after the swallow. The specific location of stasis (valleculae, pyriform sinus, or both areas) was noted and rated on a scale of 1 (coating) to 3 (complete filling of space). Supraglottic penetration was identified as entry of barium into the laryngeal vestibule superior to the true vocal folds, and aspiration was defined as entry of barium inferior to the level of the true vocal folds. The speech pathologist reviewing these cases had no prior knowledge of lesion localization. Neuroimaging Localization CT scans were performed on a Picker 1200SX Expert or a Picker PQ2000. A series of 7-mm slices was obtained from the foramen magnum to the vertex. Neuroimaging studies were reviewed and localized using Damasio and Damasio s [32] technique, which utilizes standardized templates of axial CT sections at various angles to the canthomeatal line. Parameters of the lesion were mapped out within and across each CT slice on the template. Once the lesion was mapped, the location of the lesion and cytoarchitectonic regions involved were determined using standardized templates [32,33]. CT scans were obtained within 1 week of the acute stroke. Although lesion localization on a CT scan within 1 week of the stroke may not be as circumscribed as CT scan localization at 1 2 months poststroke, the behaviors tested in this study were assessed at the same time as the CT scan was obtained in order to directly evaluate brain-behavior relationships. The insular cortex lies buried in the depths of the lateral sulcus, and is overgrown by the frontal, temporal, and parietal opercula. Therefore, the insula is not visible when viewing the lateral surface of the cerebral hemisphere, but can be visualized when the frontal, temporal, and parietal lobes are separated. The insula forms a triangular cortical area with the apex directed forward and downward. Thus, the anterior and posterior extent of the insula are radially oriented, and the precise extent of these regions is not well demarcated. However, the central sulcus of the insula can be used to divide the insula into anterior and posterior portions [34,35]. Therefore, the anterior and posterior

3 148 S.K. Daniels and A.L. Foundas: Insular Cortex in Dysphagia portions of the insula were determined based on the location of the central sulcus derived from lateral reconstructions of the lesions on standardized templates. When the central sulcus is extended ventrally onto the insular cortex, it is continuous with the central sulcus of the insula. The full extent of the insula is best visualized in the axial plane, and therefore, standard axial CT scan images were used for lesion mapping. Case Reports Case 1 The first case is a 55-year-old male who presented with a 1-day history of dysarthria and left upper extremity weakness. Previous medical history was significant for hypertension. Neurological examination was unremarkable except for a mild left facial asymmetry consistent with a left upper motor neuron (CN VII) lesion. Speech and language testing revealed dysarthria and dysphonia characterized by articulatory imprecision, strained vocal quality, and restricted volume and pitch ranges. Neither buccofacial nor speech apraxia was evident on examination. A bedside swallowing assessment revealed intermittent coughing after ingestion of liquids, but there was no wet hoarseness. Fluoroscopic Examination Oral stage functioning was intact. A mild delay in the pharyngeal swallow was evident with all volumes and consistencies. Pooling in the valleculae and pyriform sinuses was evident secondary to the delayed pharyngeal swallow. Penetration and aspiration were not apparent. Pharyngeal stasis was not present. Neuroimaging Localization Lesion mapping demonstrated a 2 cm 2 cm area of decreased attenuation limited to the anterior extent of the insula cortex in the right cerebral hemisphere. The insular lesion extended across two consecutive axial images with a small extension superiorly into subcortical white matter (Fig. 1). Case 2 The second case is that of a 63-year-old male who was admitted to the hospital following the abrupt onset of left-sided weakness and inability to walk. Past medical history was unremarkable. Neurological examination revealed anosognosia, left hemispatial neglect, left upper motor neuron VII, and left hemiparesis. Speech and language testing revealed dysarthria and dysphonia characterized by articulatory imprecision, low volume, and wet hoarseness. Neither buccofacial apraxia nor apraxia of speech was evident. A bedside swallowing examination Fig. 1. Lesion mapping revealing right anterior insula localization in Case 1. Lesion localization was performed using Damasio and Damasio s [32] method in all 4 cases. revealed anterior bolus loss, wet phonation after the swallow, but no elicitation of a cough. Fluoroscopic Examination Oral stage functioning was characterized by anterior bolus loss. A mild delay in the pharyngeal swallow yielding vallecular and hypopharyngeal pooling was noted. The delayed pharyngeal swallow was evident only with liquid consistencies and resulted in penetration into the laryngeal vestibule without evidence of aspiration. Mild to moderate vallecular stasis was noted with both consistencies. Neuroimaging Localization Lesion mapping demonstrated an area of decreased attenuation involving the anterior and posterior portions of the insular cortex in the right cerebral hemisphere. The lesion extended 4 cm in the rostral-caudal plane on axial image, with a medial-lateral depth of 2 cm. The insular lesion extended across two consecutive images, and involved small (<1 cm) portions of the frontal and temporal opercula laterally, and extended to the image superior to the insular cortex (Fig. 2). Case 3 The third case is that of a 50-year-old male who developed the abrupt onset of inability to speak 1 day after hospitalization for chest pain. Previous medical history was significant for atrial flutter and cardiomyopathy. He suffered a transient ischemic attack 7 months prior to admission with transient dysarthria; however, no abnormalities of language, deglutition, or gross motor functions were noted, and no lesions were evident on CT scan. Neurological examination on admission revealed mild distal weakness of the right upper extremity with a right Babinski response present. Speech and language examination demonstrated mild cortical stuttering char-

4 S.K. Daniels and A.L. Foundas: Insular Cortex in Dysphagia 149 Fig. 2. Lesion mapping revealing right anterior and posterior insula localization in Case 2. acterized by effortless sound and word repetitions and prolongations. Vocal quality was characterized by wet hoarseness. Buccofacial apraxia, apraxia of speech, and asphasia were not present. A bedside swallowing examination revealed intermittent wet hoarseness after ingestion of liquids. Fluoroscopic Examination Oral stage functioning was intact. A mild delay in the pharyngeal swallow was evident with vallecular and hypopharyngeal pooling. Penetration into the laryngeal vestibule was noted with liquid and semisolid consistencies, but aspiration was not identified. Laryngeal elevation was reduced in maximum anterior-superior excursion. Mild to moderate stasis with both consistencies was noted in the valleculae and pyriform sinuses. Neuroimaging Localization Lesion mapping demonstrated an area of decreased attenuation of the anterior insular cortex in the left cerebral hemisphere. The lesion extended 1.5 cm in the rostralcaudal plane, with a depth of 1.5 cm medial-lateral on each image. The full extent of the lesion involved two consecutive axial images (Fig. 3). Case 4 The fourth case is that of a 54-year-old male who developed the abrupt onset of mild word-finding difficulty. Past medical history was unremarkable. Neurological examination revealed mild word-finding difficulty; cranial nerves, sensory, motor, cerebellar, gait, station, and reflexes were intact. Speech and language testing revealed an anomic aphasia with lexical dysgraphia-dyslexia. Dysarthria, buccofacial apraxia, and apraxia of speech were not evident. A bedside swallowing examination revealed no overt swallowing difficulty. Fig. 3. Lesion mapping revealing left anterior insula localization in Case 3. Fluoroscopic Examination The VSS was unremarkable for any oral or pharyngeal stage dysfunction. All parameters evaluated during the swallowing study were intact. Neuroimaging Localization Lesion mapping demonstrated an area of decreased attenuation limited to the posterior insular cortex in the left cerebral hemisphere. The lesion extended 1.5 cm in the rostral-caudal plane, with a depth of 1 cm medial-lateral on each image with the full extent of the lesion involving two consecutive axial images (Fig. 4). Results Deglutition was evaluated by videofluoroscopy in 4 patients with discrete lesions of the insular cortex (Table 1). Lesion mapping [24 27] of neuroimaging studies revealed that 2 subjects (Cases 1 and 2) had right insular lesions, 1 restricted to the anterior insula (Case 1) and the other involving anterior and posterior insula (Case 2). Two subjects (Cases 3 and 4) had left insular lesions, 1 restricted to the anterior insula (Case 3) and the other lesion isolated to the posterior insula (Case 4). Dysphagia, as identified by VSS, was evident in 3 (Cases 1, 2, 3) of the 4 patients. Whereas dysphagia was present in the subjects with lesions involving or restricted to the anterior insula, it was not present in the only patient with a lesion restricted to the posterior insular cortex (Case 4). A delayed pharyngeal swallow was the common dysmotility pattern in the 3 patients with dysphagia and resulted in supraglottic penetration in 2 of the 3 patients. Discussion Dysphagia, as verified by videofluoroscopy, was evident in 3 of the 4 patients studied who had lesions of the insular cortex. CT scan mapping of the lesions onto stan-

5 150 S.K. Daniels and A.L. Foundas: Insular Cortex in Dysphagia Fig. 4. Lesion mapping revealing left posterior insula localization in Case 4. dardized templates demonstrated that all of the patients with dysphagia had lesions involving the anterior insula; the lesion of the only patient without dysphagia was restricted to the posterior insula. These cases support our hypothesis that the insular cortex may be an important cortical substrate of swallowing. Furthermore, the dissociation of dysphagia by anterior-posterior involvement suggests that the anterior insula may be more important than the posterior insula in swallowing. These findings are provocative in that the insula, particularly the anterior insula, has not been previously implicated with dysphagia. The anatomy and connectivity of the insula is complex, and little is known of the contribution of the insular cortex to swallowing. To our knowledge, no previous human studies have focused on the role of the insular cortex in deglutition. Due to its redundant vascular supply, focal lesions of this region are rare, and adjacent cortical and subcortical regions are generally involved and are often assumed to determine the resultant neurological deficits [20]. The insula lies deep to the sylvian fissure, and is covered by frontal, parietal, and temporal opercula. The insula of the human brain has a central sulcus, which divides the insula into anterior and posterior regions. The anterior insula consists of three short gyri (gyri breves), whereas the posterior insula consists of two long gyri (gyri longi) [36,37]. Histological studies have identified three cytoarchitectonic subdivisions of the insula: agranular, dysgranular, and granular. The anterior insula is composed of a ventral-rostral agranular field, and the posterior insula is composed of a dorsal-caudal granular field. A transitional area composed of a dysgranular field adjoins the agranular and granular subdivisions [38]. Brodmann s areas have been assigned to the agranular section of the insula whereas area 13 is located in the granular section [37]. The anterior and posterior insula differ with regard to cytoarchitectonics and connectivity; therefore, these regions probably differ functionally. The anterior insula appears to be a rich area of parallel connectivity closely associated with many cortical and subcortical areas that mediate swallowing. These areas include (1) premotor cortex; (2) gustatory, olfactory, limbic, and autonomic structures; (3) thalamus; and (4) nucleus tractus solitarius (NTS). The anterior insula has efferent connections to premotor cortex (Brodmann s area 6), which contains the motor representations for the face and mouth [20,21] with a rostral-caudal tonotopic organization [39,40]. It is well known that inferior and posterior portions of the precentral gyrus (primary motor cortex), and portions of the supplementary motor cortex are important in swallowing [review 41]. In primates, damage to the lateral precentral gyrus can disrupt oral transport and mastication [42,43], and repetitive electrical stimulation of the lateral and caudal surface of the precentral cortex can elicit swallowing alone, as well as combined mastication and swallowing [44]. Magnetic stimulation studies in humans implicate the lower precentral and posterior inferior frontal gyri for control of the oral phase, and the anterior inferior and middle frontal gyri for pharyngeal and esophageal control [45]. Thus, damage to the anterior insula may produce deglutition disorders by disrupting anterior efferent cortical pathways. In addition to connections with premotor cortex, the anterior insula has reciprocal connections with gustatory, olfactory, limbic, and autonomic structures [20,25,46 48]. In primates and rodents, the primary gustatory cortex has been localized to the frontal operculum and adjacent anterior insula [22 24]. This area, particularly the anterior insula, has separate representations for different tastes. Furthermore, insular neurons appear to be more sensitive to taste qualities than neurons of the NTS [49]. Neuroanatomical tracings in the rhesus monkey demonstrated reciprocal connections between the anterior insula and amygdala [47,48] with additional connections to the prepiriform olfactory cortex [25]. Therefore, damage to the anterior insula may produce disturbances of taste and smell that may contribute to disturbances of swallowing and eating. The anterior insula is also connected to specific thalamic nuclei. It has extensive preferential reciprocal connections with the parvicellular component of the ventroposterior medial nucleus (VPMpc) of the thalamus, which contains sensory representations for the face and oral cavity [25,26,50,51]. Furthermore, the VPMpc is the primary target of projections from rostral NTS [52]. The NTS is the medullary region important in the identification of a swallowing stimulus and is the initial relay receptor for gustatory input [52]. The NTS has projections to the nucleus ambiguus (NA), and together, the NTS and the NA form part of the medullary central pattern generator, or swallowing center [53]. Studies suggest that the anterior insula provides cortical repre-

6 S.K. Daniels and A.L. Foundas: Insular Cortex in Dysphagia 151 Table 1. Age, lesion site, and clinical and fluoroscopic results for each patient Case no. Age Lesion Neurological deficits Speech/language VSS results 1 55 R anterior insula CN VII lesion Dysarthria, dysphonia Delayed swallow 2 63 R anterior and posterior insula Anosognosia L neglect L hemiparesis Dysarthria Dysphonia Delayed swallow Penetration Stasis 3 50 L anterior insula R upper extremity weakness R Babinski response Cortical stuttering Dysphonia 4 54 L posterior insula No motor/sensory deficits Anomic aphasia, lexical dysgraphia-dyslexia Delayed swallow Laryngeal elevation Penetration Stasis Normal sentation for the NTS [25,27] and that these regions along with VPMpc may form a neural network that is the foundation for the processing of gustatory as well as visceral and autonomic information [26]. Additional animal studies in rats and rabbits have shown that the anterior insula also projects to rostral levels of the NTS [27,54,55]. Thus, this reciprocal connectivity between the anterior insula and the NTS may further influence deglutition. With its direct and indirect connectivity to the NTS, and its role as part of the cortical center of gustation, the anterior insular cortex may further participate in deglutition through this visceral sensorimotor route. In contrast to the anterior insula, the posterior insula has projections to the inferior parietal lobule, reciprocal projections with the primary auditory cortex, extensive connections with the ventroposterior inferior nucleus and the pulvinar nucleus of the thalamus, and reciprocal connections with caudal NTS [20,25,26,56]. Therefore, based on its connectivity, the functions of the posterior insula include audition, somatosensory responses, and cardiovascular autonomic responses such as blood pressure and respiratory regulation, and exclude gustatory and oromotor functions. The cases presented in this study had discrete lesions of the insula. Three of the 4 cases had lesions involving the anterior insula. Dysphagia was evident in these 3 cases, thus supporting the notion that the insula, particularly the anterior insular cortex, may be important in swallowing. These conclusions are supported by the connectivity of the anterior insula. The anterior insula has connections to the primary and supplementary motor cortices, which facilitate coordinated interaction of the tongue, face, and jaw in swallowing. The anterior insula has connections with the VPMpc of the thalamus, which has sensory representations for face and oral cavity, and is the first relay nucleus of visceral and gustatory afferents of the NTS. Additionally, the anterior insula has connections with the NTS, which is part of the medullary swallowing center. Furthermore, the anterior insula helps form the primary gustatory cortex. Theoretically, based on the connectivity to these remote regions or through inherent properties of the insula, the anterior insula may be a crucial component in the swallowing loop and may produce dysphagia when lesioned in isolation (Fig. 5). We postulate that lesions restricted to the anterior insula may produce dysphagia by disrupting the processing of gustatory input, which may in turn yield a delay in triggering a swallow response and impair pharyngeal swallowing, as demonstrated in our case studies. A delay in elicitation of the pharyngeal swallow may result from disconnection of sensorimotor information between the NTS and the anterior insular cortex. Increasing sensory characteristics of a bolus (taste, volume, temperature) have been documented as reducing the delay in pharyngeal swallow time in stroke patients [57 59]. Logemann et al. [58] identified a significant decline in the pharyngeal delay time using a sour bolus. Intensifying gustatory input may result in stronger sensory signals from the oropharyngeal cavity to the brainstem and in turn to the anterior insula thus facilitating the timing of the swallow. Lesions to the anterior insula may reduce the magnitude of sensory input, thus increasing the swallowing threshold and delaying elicitation of the pharyngeal swallow. Though lesions to other cortical, subcortical, and brainstem sites may produce changes in oral-pharyngeal transition, we suggest that isolated anterior insula lesions produce a delayed pharyngeal swallow due to reductions in the processing of sensory input, which may be primarily gustatory. In our study, the 3 patients with dysphagia had a delayed pharyngeal swallow as the common dysphagia pattern. Delayed pharyngeal swallow is one of the most common features associated with dysphagia after stroke [9,16,60]. Albeit these findings were clinically mild in patients in this study, this delay in the pharyngeal swallow was significant enough to yield supraglottic penetration in 2 of the 3 patients with dysphagia. Normal aging cannot account for this delay in the

7 152 S.K. Daniels and A.L. Foundas: Insular Cortex in Dysphagia pharyngeal swallow, which averaged between 1 and 2 sec in each of our patients with dysphagia. In a study of normal aging, Robbins et al. [61] found a positive average time for triggering a pharyngeal swallow only in the oldest group (mean age 72 years), whereas the age groups below this had a negative average time for elicitation of the swallow. The mean age of our subjects was 55.5 years. It is also unclear whether the dysphagia observed in our patients was transient or persistent as repeat VSS was not performed. Although therapeutic strategies and diet alterations were only temporarily implemented in specific patients, the 1 patient (Case 2) who presented 4 months after the stroke did have persistent dysphagia. It is important to note that the majority of research concerning the insula has involved animal studies. Controversy exists partly because of the use of an animal model, but also because different anatomical boundaries were used to delineate the anterior and posterior portions of the insula. Although human studies of the insular cortex and swallowing are lacking, Penfield and Faulk [46] did identify alterations in gastrointestinal motility and sensations associated with digestion upon cortical stimulation of the anterior insula in humans. Of note, in this larger series of 39 unilateral stroke patients from which the case studies were selected, only 4 had lesions restricted to the insular cortex. However, 4 additional patients had lesions that included portions of the insula and adjacent cortical regions; 3 of these had documented dysphagia. These data provide additional support for the notion that the insula contributes to swallowing. Further investigation with a larger patient population is warranted to support these preliminary findings. In addition, focusing on the effects of varying gustatory stimuli upon timing of the pharyngeal swallow in patients with discrete lesions of the anterior insula may facilitate understanding of the role of taste in swallowing elicitation. Animal studies with direct examination of oropharyngeal motility after discrete anterior insular lesioning may also clarify the neurophysiological and anatomical contributions of the insula to swallowing. Acknowledgments. The authors gratefully acknowledge the Research Service of VAMC, New Orleans, LA, and the critical review of the manuscript by Thomas W. Powell, Ph.D. References Fig. 5. Afferent and efferent connectivity of the insula to critical swallowing regions. 1. Meadows JC: Dysphagia in unilateral cortical lesions. J Neurol Neurosurg Psychiatry 38: , Crary MA: A direct intervention program for chronic neurogenic dysphagia secondary to brainstem stroke. Dysphagia 10:6 18, Neumann S, Buchholz DW, Wuttge-Hannig A, Hannig C, Prosiegel M, Schroter-Morasch H: Bilateral pharyngeal dysfunction after lateral medullary infarction (LMI). Dysphagia 9:263, Robbins J, Levine R: Swallowing after lateral medullary syndrome plus. Clin Comm Disord 3:45 55, Horner J, Brazer SR, Massey EW: Aspiration in bilateral stroke patients: a validation study. Neurology 43: , Horner J, Buoyer FG, Alberts MJ, Helms MJ: Dysphagia following brainstem stroke: clinical correlates and outcome. Arch Neurol 48: , Horner J, Massey EW, Brazer SR: Aspiration in bilateral stroke patients. Neurology 40: , Daniels SK, Foundas AL, Iglesia GC, Sullivan MA: Lesion site in unilateral stroke patients with dysphagia. J Stroke Cerebrovas Dis 6:30 34, Robbins J, Levine RL: Swallowing after unilateral stroke of the cerebral cortex: preliminary experience. Dysphagia 3:11 17, Robbins J, Levine RL, Maser A, Rosenbek JC, Kempster GB: Swallowing after unilateral stroke of the cerebral hemisphere. Arch Phys Med Rehabil 74: , Barer DH: The natural history and functional consequences of dysphagia after hemispheric stroke. J Neurol Neurosurg Psychiatry 52: , Gordon C, Hewer RL, Wade DT: Dysphagia in acute stroke. Br Med J 295: , Horner J, Massey EW: Silent aspiration following stroke. Neurology 38: , Horner J, Massey EW, Riske JE, Lathrop DL, Chase KN: Aspiration following stroke: clinical correlates and outcome. Neurology 38: , Teasell RW, Bach D, McRae M: Prevalence and recovery of aspiration poststroke: a retrospective analysis. Dysphagia 9:35 39, Veis SL, Logemann JA: Swallowing disorders in persons with cerebrovascular accident. Arch Phys Med Rehabil 66: , Alberts ML, Horner J, Gray L, Brazer SR: Aspiration after stroke: lesion analysis by brain MRI. Dysphagia 7: , Chen MYM, Ott DJ, Peele VN, Gelfand DW: Oropharynx in patients with cerebrovascular disease: evaluation with videofluoroscopy. Radiology 176: , Johnson ER, McKenzie SW, Rosenquist CJ, Lieberman JS, Sievers AE: Dysphagia following stroke: quantitative evaluation of pharyngeal transit times. Arch Phys Med Rehabil 73: , Mesulam M-M, Mufson EJ: The insula of Reil in man and monkey: architectonics, connectivity, and function. In: Peters A,

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