The voluntary sphincter muscles of the anorectum are. The Cortical Topography of Human Anorectal Musculature

GASTROENTEROLOGY 1999;117:32 39 The Cortical Topography of Human Anorectal Musculature GEOFFREY K. TURNBULL,* SHAHEEN HAMDY, QASIM AZIZ, KRISHNA D. SINGH, and DAVID G. THOMPSON *Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Medicine, Hope Hospital, Manchester, England; and Department of Psychology, The Royal Holloway College, Surrey, England Background & Aims: The muscles of the anorectum are important in the volitional control of continence, yet virtually no information exists on their cortical representation in humans. Methods: Topographic cortical mapping of both cerebral hemispheres was performed in 9 healthy subjects by applying suprathreshold transcranial magnetic stimulation to individual points on a scalp grid centered over the vertex and then recording the electromyographic responses from the external anal sphincter, rectum, and tibialis anterior muscles. Results: Cortically evoked anal and rectal response latencies were similar (20.2 1.7 and 19.8 1.5 milliseconds, respectively) and were shorter than those from the anterior tibialis muscle (right, 29.7 2.3 milliseconds; left, 29.9 1.8 milliseconds; P F 0.0005). Cortical mapping showed that the anal responses were bilaterally represented on the superior motor cortex (Brodmann area 4) of both cerebral hemispheres; a similar topography was found for the rectal responses. By comparison, the tibialis responses showed predominantly contralateral medial motor cortex representation. Subtle but consistent differences in the degree of bilateral hemispheric representation were also apparent both between and within individuals for the anal responses and to a lesser extent for the rectal responses. Conclusions: The anorectal musculature has bilateral motor cortex representation with similar topography, but there is intersubject variation in the degree of symmetry. The voluntary sphincter muscles of the anorectum are vital for the maintenance of fecal continence and are under strong descending control from the cerebral cortex. 1 Animal data have shown that anal sphincter contractions can be elicited by direct electrical stimulation of the superomedial aspect of the motor cortex (adjacent to the falx cerebri), 2,3 whereas data from human studies performed during neurosurgery 4,5 could not specify which anorectal muscles responded to cortical stimulation, referring to the area as the perineum. It remains, unclear, therefore, whether the pelvic muscles that make up the anorectum are represented in the same areas of the cerebral cortex or if there indeed is representation on the motor cortex for rectal musculature. Fecal incontinence is frequently encountered in instances in which there is peripheral nerve damage. However, there are instances in which fecal incontinence presents in a setting where central nervous system damage has occurred, such as in patients with stroke 6,7 or frontal lobe damage. 8 Nakayama et al. 7 found fecal incontinence primarily in patients with larger strokes and when the cerebral cortex was involved. Central motor pathways may also be important in modulating sphincter muscle function 9 (e.g., in patients who cannot relax the anal sphincter and pelvic floor properly, as in anismus). Constipation and fecal incontinence are also frequently found in patients with multiple sclerosis, 10,11 and one study of anorectal function in subjects with multiple sclerosis has suggested there may be central motor mechanisms involved. 12 The recent development of transcranial magnetic stimulation, a noninvasive technique for assessing human cerebral motor function, 13 now provides a reliable method for evaluating the corticofugal pathways innervating the striated musculature. Previous reports using this technique have described the conduction velocities and response characteristics of the anal sphincter and levator ani muscles after diffuse stimulation of the cortex 9,14 17 but have not assessed their individual cortical representations in each hemisphere. We therefore studied the topographic representation of the anal sphincter within the motor cortex by applying focal magnetic stimuli to frontocentral areas over each hemisphere. Focal magnetic stimulation techniques can stimulate discrete areas of cerebral cortex to a mapping resolution of 2 cm 2, with the central area being maximally stimulated. We also used an intrarectal electrode to take electromygraphic (EMG) recordings from within the rectum. Because cortical mapping also allows a comparison of the magnitude of representation in each hemisphere, 18 we were also able to conduct an assessment of the interhemispheric Abbreviations used in this paper: EMG, electromyographic; MRI, magnetic resonance imaging; PET, positron emission tomography. 1999 by the American Gastroenterological Association 0016-5085/99/$10.00

July 1999 CORTICAL TOPOGRAPHY OF THE ANORECTUM 33 symmetry between anal and rectal responses to cortical stimulation. Recordings of cortically evoked responses from the lower leg musculature, being contralaterally represented in the motor cortex, were used as a control for interhemispheric symmetry: the tibialis anterior muscle was thus used because it is represented on the medial surface of the cerebral cortex, distinct and inferior to the perineal area referred to by Woolsey et al. 5 Materials and Methods Subjects All subjects (n 9) were healthy adult volunteers recruited from personnel affiliated with the research units involved in the project. All claimed to have normal bowel function, and none reported a history of neurological or other illnesses. All had normal findings on examination of the perineum and anorectum before the study. This study was approved by the Salford Health Authority Ethics Committee, and all subjects gave informed written consent before participating in the study. The subjects were 8 men and 1 woman, and all were right-handed. Their mean ( SD) age was 31.7 7.9 years (range, 22 45 years). Magnetic Stimulation of the Cerebral Cortex A commercially available magnetic stimulator was used in the experiments (Magstim 200; Magstim Co. Ltd., Whitland, Dyfed, Wales). When connected to a 70-mm figure-eight coil (model type 9790; Magstim Co.), this system allows the generation of maximal magnetic fields of 2.2 T that are focused at the cross point of the coil. The area of cortex stimulated by the figure-eight coil is 2 cm 2, ideal for mapping purposes, and will preferentially activate interneurons of the motor cortex (transsynaptic stimulation). One of the natural advantages of magnetic stimulation is its ability to stimulate neural tissue deep to the scalp, skin, or bone with virtually no signal attenuation. Thus, lower energies are required to excite nerve fibers, which makes the technique almost painless. A single pulse of transcranial magnetic stimulation to the scalp, with the center of the coil at the cranial vertex, penetrates brain tissue to a depth of 4 5 mm, 19 and even at high intensities there is little evidence that the stimuli penetrate beyond the gray matter of the cortex. Because cortical excitation produced by magnetic stimulation is dependent on coil orientation relative to the scalp surface, the figure-eight coil was always placed with the anterior edge of the cross point positioned over the site of interest and with the handle pointing backward (for the midline grid points) or at an angle of 45 tangential to the scalp surface (for lateral grid points), as described by Mills et al. 20 Anorectal and Anterior Tibial EMG Responses Anal sphincter EMG responses were recorded by using an anal plug electrode system with three Ag/AgCl EMG plate electrodes arranged radially 120 apart (EPS-30; Farrall Instruments, Inc., Grand Island, NE) and positioned in the anal canal. Rectal EMG responses were recorded from a single pair of Ag/AgCl ring electrodes (interelectrode distance, 1.5 cm) mounted on a 5-mm-diameter catheter that was inserted into the rectum through the center of the anal plug (length, 5.5 cm) and positioned so that the rectal electrodes were 10 cm from the outside edge of the anal plug at the anal verge. The anal plug, constructed of hard plastic, was orientated in the anal canal to position the rectal catheter 4.5 cm above the inside edge of the anal plug against the anterior wall of the distal rectum close to the pelvic floor muscles. Anterior tibialis muscle responses were recorded by using a pair of Ag/AgCl surface EMG electrodes (no. 13L20; Dantec, Tonsbakken, Skovlunde, Denmark) placed over each muscle with an interelectrode distance of 1 cm. The EMG responses from all four sites were recorded with a multichannel EMG recording system (Counterpoint; Dantec) using filter settings of 20 Hz and 2 khz, a sweep length of 100 milliseconds, and a full-scale deflection of 200 2000 µv. Electrode contact was monitored during the study at regular intervals by using real-time EMG responses to voluntary contractions of each muscle group. Topographic Mapping Procedure A12 8 cm grid, with rows of points 2 cm apart anteroposteriorly and 1 cm apart mediolaterally, was superimposed onto a transparent plastic sheet and attached to a surgical hood that was securely fastened to each subject s head. The grid was positioned to allow stimulation of sites up to 6 cm lateral and anterior to the vertex and up to 2 cm posterior to the vertex (Cz on the 10 20 international system 21 ) over both hemispheres. During the mapping procedure, subjects reclined on a comfortable examination couch, with their legs flat. After a digital examination to ensure that the rectum was empty, the EMG anal plug was inserted, and the rectal catheter was passed through the lumen of the anal plug and sited on the rectal wall 10 cm above the anal margin. Protocols Study 1: Topographic mapping of the cortical representation of the anorectum. All 9 subjects participated in this study. First, to determine the threshold intensity for cortical stimulation, a preliminary mapping study was performed. This was conducted by discharging the figure-eight coil with a stimulation intensity of 2.2 T (100% stimulator output) over the medial points of the scalp grid surrounding the vertex. By this means, the sites evoking maximal EMG responses were identified, and their positions were noted for each hemisphere. After identification of the sites that gave the largest responses, cortical stimulation of these sites was repeated, starting at a subthreshold intensity of 0.6 T (30% stimulator output) and increasing in 0.1 T steps until intensities were found that first evoked quantifiable anal, rectal, and tibial EMG responses in at least 3 of 6 consecutive trials. These values were defined as the stimulation threshold intensities.

34 TURNBULL ET AL. GASTROENTEROLOGY Vol. 117, No. 1 After these thresholds had been determined, the stimulation coil was repositioned over each point on the scalp grid (the order of which was randomized between each subject), and the coil was discharged at 0.4 T (20% stimulator output) above the predetermined threshold intensity. By applying this constant, albeit relative, level of stimulation above that subject s threshold intensity, a uniform level of neural stimulation can be achieved and assessable EMG responses recorded. The use of 120% of the threshold intensity for mapping is recommended by the guidelines proposed for magnetic stimulation technique, 22 because at this level the maps generated are considered to give a relatively reliable estimate of the representative size of the motor cortex area devoted to a muscle group. Three stimuli, at least 15 seconds apart, were delivered at each point, and the EMG responses from each muscle group were recorded. Study 2: Reproducibility of the cortical topography. To provide an assessment of reproducibility, 3 subjects who participated in study 1 underwent a second identical mapping study at least 14 days after the first. Study 3: Coregistration of topographic scalp data with surface-rendered magnetic resonance brain images. In 3 subjects, the cortical structures underlying the grid points from which EMG responses were obtained were identified by performing magnetic resonance imaging (MRI) of the head with a 1.0 T field strength Magnetom Impact Scanner (Siemens, Erlangen, Germany). The topographic data obtained for each of the 3 subjects were then coregistered with their surface-rendered MRI brain image by using magnetic source digitalization (Polhemus 3-space Isotrak system; Kaiser Aerospace Inc., Colchester, VT) of each of the scalp grid coordinates. 23 Those interested in these techniques are referred to an excellent review of their application to study of the brain-gut axis by Aziz and Thompson. 24 Data Analysis For each grid point, the mean value of the three EMG responses evoked for each muscle group was calculated. In using the averaged data, any potential trial-to-trial variation in the shape of the response tracing can thus be reduced. Definition of Terms Latency. Latency was the interval from the onset of the stimulus to the onset of the individual muscle EMG response, expressed in milliseconds. To provide a single figure for analysis in each subject, the shortest five latencies for each muscle group were identified, and the mean value was calculated. Amplitude. Amplitude was the peak-to-peak voltage of the EMG responses, expressed in microvolts. Only responses of 5 µv were used. A mean amplitude value for each subject was calculated by using the five largest responses. Magnitude of representation. The magnitude of representation was the number of sites on the scalp grid over each hemisphere (including midline sites) from which an EMG response was obtained. Interhemispheric asymmetry. The intraindividual hemispheric magnitudes of representation were calculated as a percentage of each hemisphere s responses (number of grid sites) to the total number of responses from both hemispheres and were considered asymmetric if the larger hemisphere representation was 60%. Construction of Topographic Scalp Maps Scalp maps representing the area of response for each muscle group were generated in each subject by assigning to each scalp grid point an EMG response amplitude. These data were then imported into the UNIRAS interactive program UNIMAP (AVS/UNIRAS Systems, Waltham, MA) and were interpolated onto regular two-dimensional grids. Statistical Tests The Wilcoxon rank sum test was used to compare data for significance, and the Spearman rank correlation was used to assess correlation of the paired data. Amplitudes from each muscle group in each patient were converted into a ratio of response and visually compared after cortical maps of the amplitude response had been generated. The statistical package Instat (GraphPad Software, San Diego, CA) was used as appropriate. Data are expressed as means SD, unless stated otherwise, and a P value of 0.05 was taken to indicate statistical significance. Results In all subjects, cortical stimulation (mean threshold intensity, 2.0 0.1 T) evoked assessable biphasic or triphasic EMG tracings in each muscle group. Examples of the averaged responses are presented in Figure 1. Response Characteristics Latencies. There were no consistent latency differences between anal sphincter and rectal responses. The mean anal latency was 20.2 1.7 (SD) milliseconds, and the mean rectal latency was 19.8 1.5 milliseconds, significantly shorter than the mean right tibial latency of 29.7 2.3 milliseconds and the mean left tibial latency 29.9 1.8 milliseconds (P 0.0005). As expected, there was a strong latency correlation between the right and left tibial responses (Spearman correlation r 0.91; P 0.0001). There was also a strong correlation between the anal and rectal latency responses (Spearman correlation r 0.71; P 0.005). Amplitudes. The individual amplitudes of the responses for each muscle studied are shown in Table 1. Amplitude responses were more variable between subjects, the anal and rectal responses being smaller than the leg responses. Scalp Topography Figure 2 illustrates the scalp topography of the anal and rectal responses in 3 subjects. In general,

July 1999 CORTICAL TOPOGRAPHY OF THE ANORECTUM 35 responses from both muscle groups were localized either adjacent to or anterior to the vertex and showed similar, but not identical, topographic representation, with little evidence for discrete somatotopic organization on the Figure 1. Individual examples of the averaged EMG responses recorded from the anal sphincter, rectum, right tibialis, and left tibialis muscles after cortical stimulation. (A) EMG responses in all four muscle groups after stimulation of a site close to the vertex of the scalp. The morphology of each response is different, suggesting that each was generated from an independent source and that the latency of the anal sphincter response is longer than that of the rectal response, both being shorter than the tibial responses. Arrows indicate the onset of anal and rectal responses. (B) EMG responses after stimulation of a site over the right hemisphere. Both anal and rectal responses have been evoked, whereas, as expected, only the contralateral left tibial response is evoked. (C) EMG responses after stimulation of a site over the left hemisphere. Again, both anal and rectal responses are evoked, whereas only the contralateral right tibial response is evoked. (D) Responses to stimulation of a second midline scalp site. In contrast to the responses shown in A, the rectal response has been evoked in the absence of an anal response, indicating that the rectal response was unlikely to have been induced by contraction of the anal sphincter. Table 1. Individual Cortically Evoked Response Amplitude Characteristics Subject Study Anal mean ( V) Rectal mean ( V) Right leg ( V) Left leg ( V) 1 1 38.0 50.0 355 384 2 28.2 37.9 602 494 2 1 16.1 36.5 377 144 2 16.1 28.0 585 631 3 1 28.9 26.4 359 289 2 30.8 26.7 318 210 4 1 14.3 44.2 137 225 5 1 33.3 35.2 444 113 6 1 12.3 55.8 119 230 7 1 25.4 19.4 104 58.6 8 1 36.1 28.1 474 185 9 1 17.0 16.1 303 354 motor cortex. Although both the anal and rectal responses could be evoked by stimulation of either hemisphere, indicating a bilateral representation, subtle differences in the magnitude of representation from the two hemispheres were observed. Compared with the anterior tibialis responses, there is only 1 subject who lateralized anal representation to the left hemisphere (subject 2, Tables 2 and 3), with a hemisphere asymmetry of 60%. Two additional subjects (subjects 6 and 8, Tables 2 and 3) had clearly asymmetric anal sphincter representation, with 67% and 61% of the responses from the right hemisphere; anal representation appears more symmetric in the other 6 subjects. By comparison, only 1 subject lateralized the rectal response representation to the left hemisphere (subject 3 in Tables 2 and 3), with a hemisphere asymmetry of 61%. The rectally recorded responses in the other 8 subjects had more equal representation in both hemispheres. Responses from the tibialis anterior muscles were also located in medial sites adjacent to the vertex, and they overlapped with the anorectal representations. Not surprisingly, the right and left leg muscles showed clear contralateral hemisphere lateralization, although some ipsilateral hemisphere responses were observed (probably related to stimulus spread; Tables 2 and 3). The left hemisphere/right leg representation was usually larger than the right hemisphere/left leg representation, reflecting the right-handed bias in this study group. Reproducibility Comparisons of the topographic maps between the two studies indicated that the magnitude of representation was similar in each of the 3 subjects investigated. In addition, the interhemispheric differences in representation showed a reasonable degree of consistency for both the anal sphincter and the rectal responses, being always in the same direction (Tables 2 and 3).

36 TURNBULL ET AL. GASTROENTEROLOGY Vol. 117, No. 1 Table 2. Topographic Mapping Data for Each Subject Showing the Magnitudes of Representation Magnitude of representation (no. of grid points) Right hemisphere Left hemisphere Subject Study no. Anal Rectal Right leg Left leg Anal Rectal Right leg Left leg 1 1 17 19 6 24 15 18 20 8 2 19 21 11 27 19 20 22 6 2 a 1 10 11 8 10 13 15 15 4 2 8 18 12 23 12 23 28 8 3 b 1 12 9 4 11 11 14 12 6 2 8 13 6 15 9 18 20 5 4 1 4 15 7 15 4 17 18 6 5 1 18 20 8 19 17 19 21 5 6 c 1 20 24 6 24 10 17 18 4 7 1 23 22 7 16 18 16 19 2 8 c 1 22 15 9 15 14 13 15 1 9 1 13 12 7 16 15 15 21 7 NOTE. See Definition of Terms for explanation of cortical lateralization. a Subject lateralized anal responses to the left hemisphere. b Subject lateralized rectal responses to the left hemisphere. c Subject lateralized anal responses to the right hemisphere. Coregistration Data An example of the coregistered data in 1 subject is shown in Figure 3. For all 3 subjects who had MRI scans, the colocalization of the cortical maps with the MRI scans showed the maximal response for both the anus and rectum to overlay the precentral gyrus of the motor cortex (Brodmann area 4) just anterior to the central sulcus, corresponding to the area previously described by Woolsey et al. 3 for perineal motor localization in animals. Discussion These data show, for the first time, that the human anal sphincter has discrete motor representation within both hemispheres of the cerebral cortex, possibly implying a bilaterally integrated pattern of recruitment at the cortical level during the volitional control of anal continence. In addition, our observation that the representation for the anal sphincter is located at the most medial aspect of the superior motor cortex, adjacent to the interhemispheric fissure, is consistent with data from both animal 2,3 and human studies 4,5,25 that used direct cortical stimulation methods and have shown that this muscle is represented on the mesial motor strip (Brodmann area 4). Indeed, tracer studies in rats 26 have shown strong projections from the motor cortex to the sacrocaudal spinal cord, which innervates the pelvic muscles, whereas functional positron emission tomography (PET) imaging 27 during the task of pelvic floor straining in women has also shown activation of the superomedial precentral gyrus. This PET study raised the intriguing possibility that a difference might exisit between men and women, although the similarity of findings in our study (consisting of mostly male subjects) and those in Table 3. Hemisphere Symmetry as a Percentage for Each Subject Responses from right hemisphere (%) Responses from left hemisphere (%) Subject Study no. Anal Rectal Right leg Left leg Anal Rectal Right leg Left leg 1 1 53 51 23 75 47 49 77 25 2 50 51 33 82 50 49 67 18 2 1 43 42 35 71 57 58 65 29 2 40 44 30 74 60 56 70 26 3 1 52 39 25 65 48 61 75 35 2 47 42 23 75 53 58 77 25 4 1 50 47 28 71 50 53 72 29 5 1 51 51 28 79 49 49 72 21 6 1 67 59 25 86 33 41 75 14 7 1 56 58 27 89 44 42 73 11 8 1 61 54 37 94 39 46 63 6 9 1 56 44 25 70 54 56 75 30 NOTE. See Definition of Terms for explanation of hemispheric percentage score for each muscle.

July 1999 CORTICAL TOPOGRAPHY OF THE ANORECTUM 37 Figure 2. (A C ) Topographic scalp maps of the cortical representation of the anal and rectal responses for 3 subjects. All plots are oriented as viewed from above, with the vertex of each plot marked with an X. Scale indicates the percentage of the amplitude of the maximum response evoked from either hemisphere for each muscle group in each subject. Subject in A has bilateral anal and rectal representation, whereas subjects in B and C show clear lateralization of both the anal and rectal responses to the left and right hemispheres, respectively. the PET study would make this unlikely. Thus it appears that the primary motor control of anorectal function does reside in the mesial region of the motor strip. Our data also provide the first description of the cortical topography of responses from within the human rectum, indicating that it appears to have a separate, but overlapping, medial motor cortex representation compared with the anal sphincter. The question that arises, however, is which striated muscle structure within the pelvis generated these responses. The most plausible explanation for these responses is that they arose from the pelvic floor muscles via conduction of the EMG signal through the rectal wall, because motor cortex stimulation predominantly activates pyramidal motor pathways to striated muscle (including the levator ani muscles), 19 and the only striated muscle in immediate proximity to the intraluminal electrode within the rectum is that of the pelvic floor. It could be argued, however, that these responses might simply represent an EMG artifact induced by catheter movement generated in the rectum, a consequence of anal sphincter contraction. This seems unlikely for the following two reasons. First, we identifed scalp sites where rectal responses could be evoked in the absence of an anal sphincter response (Figure 1D), a finding difficult to reconcile if the rectal responses were dependent on anal sphincter activation. Second, we observed that although the scalp topography of the anal Figure 3. Individual data from 1 subject shown as a series of right lateral oblique surface-rendered brain MRI images onto which scalp map data have been colocalized. Arrow indicates central sulcus. The areas of cortex under the colocalized representation of the anal, rectal, right leg, and left leg responses are shown. The responses from all four muscle groups localize to the superomedial motor cortex (Brodmann area 4), but they have different morphologies and extents of representation. In particular, in this individual, the anal and rectal responses have bilateral representation, whereas the leg responses show clear lateralization to the contralateral hemisphere.

38 TURNBULL ET AL. GASTROENTEROLOGY Vol. 117, No. 1 and rectal representations overlapped, they were neither at identical sites nor directly similar in contour shape, which is inconsistent with the hypothesis that anal sphincter contraction generated both responses. It should also be emphasized that the anal plug used for recording sphincter EMG was constructed of hard plastic with the rectal catheter inserted through the plug lumen, thus isolating the rectal catheter from any artifact associated with anal sphincter contractions. A further, but improbable, explanation for the rectal responses is that they could have originated from the smooth muscle of the rectum. This is unlikely, because the elicitation of myoelectric activity within the smooth muscle fibers of viscera by single pulse magnetoelectric stimulation of motor cortex has not been shown previously, 19,28 and the pattern of EMG response that was found was more typical of striated muscle. We observed that within individuals there were subtle but consistent differences in the motor representation of anal and rectal responses between hemispheres. From our data, it appears that the anal sphincter may have greater representation in the right hemisphere of right-handed subjects, whereas the rectal responses tend to be more bilaterally represented. It could be suggested, however, that these interhemispheric differences are simply a reflection of differences in the ability of the magnetic stimulus to access and thus to excite the relevant motor neurons on the two hemispheres, a consequence of their anatomic position with respect to the surface gyri and sulci. There is, nevertheless, evidence that unilateral cerebral injury, such as hemiplegic stroke, leads to defecatory impairment independent of mental state or immobility. 6,7,29 This observation would be difficult to explain if the muscles of continence were equally innervated from motor areas of both hemispheres, and it suggests that cortical damage to the hemisphere dominant for sphincteric control might be damaged in such cases. The anatomic and functional relevance of anorectal musculature lateralization within the cortex clearly merits further exploration, and indeed there is evidence from magnetoencephalographic studies of human anal sphincter sensation to indicate that at least in sensory areas of the cortex there is laterality. 30 However, in the absence of direct intracortical stimulation techniques, this possibility must remain the subject of speculation. It is of relevance to note that our mapping of the cortical representation of the anterior tibialis muscle overlapped with the anal and rectal muscle responses, presumably a consequence of the inability of the magnetic stimulus to access motor fields within the medial wall of the precentral cortex adjacent to the falx cerebri. Despite this overlap, the tibialis responses were clearly lateralized to the contralateral hemisphere, lending further support to our observation that the interhemispheric asymmetry for the anorectal musculature was a true finding. In relation to the specific location of the anorectum with the motor homunculus of the gut, parallel studies of esophageal and pharyngeal responses to cerebral magnetic stimulation have also been performed by our group and were found to be quite distinct from the anorectal and tibialis anterior responses, being clearly more lateral and anterior. 31,32 Our findings begin to explain why neurological diseases alter anorectal function especially when there is an isolated injury to the central nervous system. 6 11,29 For example, an understanding of the cortical organization of the anal sphincter mechanism might be important in explaining disordered sphincter muscle control such as anismus or pelvic floor dyssynergia. In addition, similar studies could be conducted to evaluate the cortical representation of the urethral sphincter, comparing the central neural organization of the anal and urethral sphincters to see whether these muscles are selectively disrupted in patients with both fecal and urinary incontinence after cerebral injury. From a clinical perspective, the method is easy to perform, is well tolerated by subjects, and can be applied repeatedly, allowing longitudinal assessments of the motor pathways from cortex to anorectum in patients with disorders of continence. However, further studies need to be performed to evaluate whether these techniques provide valuable information about cortical function and incontinence after injury that may predict the recovery of continence. In conclusion, we have found that anal musculature is bilaterally represented in the superomedial motor cortex but appears to display subtle interhemispheric differences. 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Electroencephalogr Clin Neurophysiol 1996;100:126 140. 26. Masson RL Jr, Sparkes ML, Ritz LA. Descending projections to the rat sacrocaudal spinal cord. J Comp Neurol 1991;307:120 130. 27. Blok BF, Sturms LM, Holstege GA. PET study on cortical and subcortical control of pelvic floor musculature in women. J Comp Neurol 1997;389:535 544. 28. Aziz Q, Rothwell JC, Barlow J, Hobson A, Alani S, Bancewicz J, Thompson DG Esophageal myoelectric responses to magnetic stimulation of the human cortex and the extracranial vagus nerve. Am J Physiol 1994;267:G827 G835. 29. Brittain KR, Peet SM, Castleden CM. Stroke and incontinence. Stroke 1998;29:524 528. 30. Stottrop K, Schnitzler A, Witte OW, Freund HJ, Enck P. Cortical representation of the anal canal (abstr). Gastroenterology 1998; 114:A843. 31. Hamdy S, Aziz Q, Rothwell JC, Singh KD, Barlow J, Hughes DG, Tallis RC, Thompson DG. The cortical topography of human swallowing musculature in health and disease. Nat Med 1996;2: 1217 1224. 32. Aziz Q, Rothwell JC, Hamdy S, Barlow J, Thompson DG. The topographic representation of eosphageal motor function on the human cerebral cortex. Gastroenterology 1996;111: 855 862. Received May 12, 1998. Accepted April 12, 1999. Address requests for reprints to: Geoffrey K. Turnbull, M.D., Gastroenterology Unit, Room 927, Queen Elizabeth II Health Sciences Centre, 1278 Tower Road, Halifax, Nova Scotia, Canada, B3H 2Y9. Fax: (902) 473-4406. Supported by a Royal College of Physicians and Surgeons of Canada Detweiler Travelling Fellowship and a Canadian Society of Clinical Investigation/Schering Fellowship (to G.K.T.). Dr. Hamdy is a Medical Research Council Training Fellow, and Dr. Aziz was a British Digestive Foundation Training Fellow. Presented in part at the British Society of Gastroenterology Meeting, Edinburgh, Scotland, September 1994. The authors thank J. Barlow and A. Hobson for their assistance, S. Larkin in the Manchester University Computer Graphics Unit for producing the color maps, and Dr. J. Rothwell, Medical Research Council Human Movement and Balance Unit, Institute of Neurology, for his advice on cortical mapping.