Medical College of Wisconsin Digestive Disease Center, Division of Gastroenterology and Hepatology, Department of Medicine and Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
Submitted 2 May 2003 ; accepted in final form 18 August 2003
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
fecal continence; functional magnetic resonance imaging
In addition to physiological importance, a better understanding of the cortical control of the continence mechanism has clinical significance because fecal incontinence has been reported in patients following cerebrovascular accident (5, 33) and injuries of the frontal lobe (46).
The aims of the present study were therefore to determine the areas of the human cerebral cortex involved in voluntary contraction of the external anal sphincter and the relationship between cerebral cortical activity and two effort levels of willful contraction of this sphincter.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Magnetic resonance imagery scanning. Gradient echo planar magnetic resonance (MR) images were acquired using a 1.5 Tesla GE Signa System (General Electric Medical Systems, Waukesha, WI) equipped with a custom three-axes head coil designed for rapid gradient field switching and a shielded transmit/receive birdcage radiofrequency coil. The MR scanner and head coil were used to acquire a time course of echo planar images over the entire brain volume. In each of 13 contiguous 10-mm thick sagittal slices, 120 images were captured with an echo time (TE) of 40 ms and a repetition time (TR) of 1,000 ms. Echo planar images were 64 x 64 pixels over a 240-mm field of view (in-plane resolution of 3.75 mm). High resolution spoiled gradient recalled acquisition at steady-state images were also obtained consisting of 124 1.2-mm-thick slices (TE of 76 ms, TR of 16,000 ms). These high-resolution anatomic images were used for subsequent superposition of cortical activity regions derived from the lower-resolution echo planar blood oxygenation level-dependent (BOLD) contrast image data. All MR imagery (MRI) data were stereotaxically transformed to the Talairach-Tournoux coordinate (42) system for comparison and display purposes.
Image registration, data analysis, and movement correction. To compensate for subtle changes in head position over the course of the MRI scanning sessions, an algorithm for three-dimensional (3-D) volume registration was used. (9) This algorithm is designed to be efficient at fixing motions of a few millimeters and rotations of a few degrees. With the use of this limitation, the basic technique is to align each volume in a time series to a fiducial volume (usually an early volume from the first imaging run in the scanning session). The fiducial volume is expanded in a first-order Taylor series at each point in the six motion parameters (3 shifts, 3 angles). This expansion is used to compute an approximation to a weighted linear least-squares fit of the target volume to the fiducial volume. The target volume is then moved according to the fit, and the new target volume is refit to the fiducial. This iteration proceeds until the movement is small. Effectively, this is gradient descent in the nonlinear least-squares estimation of the movement parameters that best make the target volume fit the fiducial volume. This iteration is rapid (usually only 2-4 iterations are needed), because the motion parameters are small. It is efficient, based on a new method using a four-way 3-D shear matrix factorization of the rotation matrix. It is also accurate, because Fourier interpolation is used in the resampling process. On the Intel workstation used for this project, a 64-pixel x 64-pixel x 13-slice volume can be aligned to a fiducial in <1 s.
All functional MRI (fMRI) signal analysis was carried out using the Analysis of Functional NeuroImaging (AFNI) software package developed by Robert Cox of the National Institute of Mental Health (8). This software allows the user to visualize a 3-D representation of two-dimensional MRI data in an interactive Unix-based X11 Windows format. In addition to providing a straightforward method for image visualization, the AFNI package also provides the statistical tools for testing the correlation of fMRI signal waveforms to applied stimulation protocols. A nonbiased method of detecting cortical regions that exhibit BOLD changes is achieved by applying a cross-correlation technique that compares an idealized waveform with an actual MRI-generated magnetic signal time course. This technique has been used in many fMRI investigations including studies of cortical response to esophageal stimulation. A threshold correlation coefficient of 0.7 was used as a limiting criterion for accepting an fMRI time course as being correlated to the stimulus paradigm.
AFNI analyses and statistical comparisons were performed on a Pentium III-based PC (Southwest Computers, Houston, TX) with dual-boot capabilities for running both the AFNI software out of a Linux operating system and SigmaStat statistics software (SPSS, Chicago, IL) out of the Microsoft (Redmond, WA) Windows 98 operating system.
Data are represented as means ± SE unless stated otherwise. Gender comparisons of cortical activity volume and temporal signal characteristics were performed using unpaired Student's t-testing with Bonferroni correction for multiple comparisons. Intragroup comparison of cortical activity volume and temporal characteristics of fMRI signals were done using analysis of variance with paired Student's t-test and Tukey's correction.
External anal sphincter contraction effort. All subjects participated in a similar paradigm-driven external anal sphincter contraction protocol. All contraction scans were performed in a block trial format alternating 10 s of sustained external anal sphincter contraction with 10 s of rest.
Studies were carried out in two stages. Stage 1 was monitored contraction, in which we studied 10 healthy volunteers (5 males, 5 females). Sphincter contraction was monitored by recording pressure using a catheter-affixed, air-filled bag positioned within the anal sphincter segment. The latency of sphincter contraction to recorded pressure signal upstroke was tested before each scanning session by having the subject verbally report the instant of a practice sphincter contraction while we monitored the pressure recording 30 ft from the magnet. We observed the upstroke in recorded pressure to be concurrent with the subject's reported instant of sphincter contraction. Subjects participating in the stage 1 studies performed maximal and submaximal effort external anal sphincter contractions during two different fMRI scanning sequences. These subjects were instructed before the submaximal effort scans as to what level of effort produced a bag pressure that was approximately one-half the recorded maximum effort pressure. Subjects performed 10 s of sustained contraction followed by 10 s of rest for a total of five pairs per scanning period. Before each fMRI scanning sequence, subjects were told that they would be cued to contract their anal sphincter to the desired level by a light tap on the right lower leg and to then stop the contraction when cued by another light tap on the right leg. This cuing procedure has been used previously and shows no confounding fMRI signal activity. (24)
At the conclusion of stage 1 studies, four subjects performed three additional scans in which maximum contraction followed by rest were alternated with submaximum contractions followed by rest in the same scanning period.
Stage 2 was self-reported contraction without catheter-affixed balloon. To ascertain the effect of the presence of a measuring device on topography of cortical representation of external anal sphincter contraction, we studied an additional four male and three female healthy subjects. They performed six scans of alternating 10-s intervals of self-determined maximum external anal sphincter contraction and rest in the absence of the pressure-measuring device.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
|
|
|
Stage 1: comparison of objectively monitored maximal and submaximal external anal sphincter contractions. During maximal anal sphincter contraction, cerebral cortical fMRI signal changes were detected in the sensory motor cortex in 10 of 10 subjects, cingulate gyrus and prefrontal cortex in 7 of 10, parietooccipital activity in 9 of 10, and insular cortex in 6 of 10 subjects. The volumes of regional cortical activity associated with voluntary maximum external anal sphincter contraction and its accompanied maximum percent change in signal intensity are shown in Table 1. Cerebral cortical activity during submaximal external anal sphincter contraction was detected in the majority but not all individuals who exhibited activity with maximum anal sphincter contraction (Table 2). The volume of cortical activity and its related maximum percent fMRI signal changes for submaximal external anal sphincter contraction are shown in Table 3.
Comparison of the volume of cerebral cortical activity during maximal and submaximal anal sphincter contraction showed significant differences in the total cortical activity volume between the two tested effort levels (Fig. 4; P < 0.05). Comparison of regional cortical activity volumes between maximal and submaximal contraction, however, showed significant differences between effort levels only for the sensory motor cortex (P < 0.05). The differences for parietooccipital, cingulate gyrus, and prefrontal cortices did not reach statistical significance. The fMRI activity volume for the insular cortex was virtually identical between the two effort levels (Fig. 4). Similar to the findings for total activity volume, the maximum fMRI percent signal changes associated with maximal external anal sphincter contraction (4.8 ± 0.1) were significantly higher (P < 0.05) than those of submaximal contraction (2.2 ± 0.1).
|
Comparison of the incidence of cortical activity in various regions associated with maximal and submaximal anal sphincter contraction between male and female subjects (5 males, 5 females) using a Fischer exact test revealed that insular activation was significantly more prevalent among female subjects compared with male subjects (P < 0.05). Insular activity was observed in 100 vs. 20% for maximal and 80 vs. 20% for submaximal anal sphincter contraction among female and male subjects, respectively. There were no gender differences for activation incidence in other studied brain regions.
Stage 2. Self-reported maximum external anal sphincter contraction without the presence of a measurement device resulted in changes in cerebral cortical blood oxygenation level in four distinctive areas of the brain, similar to studies conducted with the presence of the manometric device. The cortical activity was detected in the sensory motor cortex in seven of seven subjects, the cingulate gyrus and prefrontal regions in four of seven, the parietooccipital area in five of seven, as well as the insular cortex in three of seven subjects (Table 4). Because the studied groups were different, no comparison could be done on magnitude of volume of cortical activation or its maximum percent fMRI signal change in activity between monitored maximum contraction and self-reported maximum contraction.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
We asked the volunteers to induce two levels of anal sphincter contraction; the maximum level of contraction that they could generate and a second level of contraction approximately one-half the maximum. Applying these two levels of effort was easily learned by the subjects before they were placed in the scanner. Applying any predetermined level of effort in contracting the external anal sphincter requires planning, control, and execution. Regional cortical activity observed in this study in areas other than the primary motor cortex, which previously has been shown to be involved in external anal sphincter contraction (44), may reflect these requirements. For example, activity detected in Brodmann area six corresponds to the supplementary motor areas that have been thought to be involved in the execution of simple tasks (37). Whereas the anterior cingulate gyrus activity detected in this study is in agreement with previous reports implicating this region of the brain in many motor behaviors, especially those that concern novel or difficult tasks (20), it is also believed that the anterior cingulate gyrus is involved in attention to body parts (36). Both of these areas have been reported to participate in control of the pelvic floor musculature (4). Representation of the pelvic floor muscles in the primary motor cortex has been previously demonstrated using direct stimulation of this region in humans as well as various animal species.
Stimulation of the upper area of the precentral gyrus is reported to cause protrusion of the anal canal and closure of the anal sphincter in monkeys (13, 45) and chimpanzees. Transcranial electrical stimulation of the primary motor cortex stimulated the external anal sphincter (12, 28). Transcranial magnetic stimulation in humans has shown that the anorectal muscles are represented bilaterally in the motor cortex (44). The finding of the present study of voluntary contraction of the external anal sphincter corroborates the involvement of the primary and secondary motor cortices in motor control of the external anal sphincter. However, study findings indicate that motor control of the external anal sphincter involves several other regions in addition to the motor cortex.
The external anal sphincter is part of the pelvic floor musculature that also includes the levator ani, puborectalis, and the external sphincter of the urinary bladder. Although each one of these muscles has a primary function, all are closely related and show concurrent activity during other functions. For example, during pelvic straining and during voluntary external anal sphincter contraction, other muscles including the levator ani and puborectalis unintentionally contract along with the external anal sphincter. Therefore, areas of the cerebral cortex activated during the present experiments may also represent function of muscles other than the external anal sphincter. This issue also exists with experiments using direct cortical stimulation. Because the above mentioned muscles of the pelvic floor were not recorded during these cortical stimulations, the specificity of cortical areas reported in these studies including the present report to the external anal sphincter is not conclusive. However, from a functional point of view, these short-comings are of less importance, because the external anal sphincter usually contracts voluntarily in concert with other muscles involved in continence. From this perspective, areas of the brain identified in this study practically may represent the voluntary continence mechanism of the anorectum and not only the external anal sphincter.
Previous studies (7, 39, 40) of simple motor tasks such as finger tapping have documented activation of multiple cortical regions. Animal studies have shown correlated neuronal discharge between the sematosensory and motor cortex (31) as well as between the thalamus and sensory cortex (21) and within and between hemispheres (34). These correlated or synchronous activities of different regions of the brain for performing a motor task are believed to be important for sensory motor integration and memory (25). Our findings also support the fact that generating external anal sphincter contraction requires correlated activities of various cortical regions, including primary and secondary sensory motor cortex as well as association areas of the brain, such as the cingulate gyrus and parietooccipital lobe. Of interest is the activity of the insular cortex, predominately found in female subjects, during external anal sphincter contraction.
The role of the insular cortex in voluntary motor activity is inconclusive. Studies of cortical activity during finger flexion have reported no activity in the insula (14) using combined fMRI and electromyography. Similarly, positron emission tomographic (PET) studies during arm flexion have not reported changes in blood flow in the insular cortex (38). Illusionary arm flexion/extension has been reported to be associated with insular activity (32). Additionally, studies of coordinated hand movement and simultaneous hand and foot movement have reported insular activity using PET (11). Activation of the insula is not confined to motor activity of the extremities. Volitional swallowing and swallow-related motor tasks such as lip pursing, tongue rolling, and jaw clenching have also been associated with activity in the insula (22, 24, 30, 43).
Although not a part of the original aims of this study, results indicate that there are significant differences in recruitment of the insular cortex during external anal sphincter contraction between male and female subjects. Gender differences in cortical processing of intestinal visceral sensations have been reported previously (2, 23). The findings of the present study support the notion of gender differences with regard to voluntary contraction of the external anal sphincter and indicate a broader spectrum of differences than previously thought regarding cortical control of intestinal function between males and females.
Previous studies (16, 17) of the primary motor cortex in monkeys have reported a direct relationship between exerted force and discharge rate of the single neurons. A direct relationship between flexion force of the index finger and the increase in cerebral blood flow in the motor cortex detected by PET has also been reported (10). In this study, activity was observed in four regions of the brain including contralateral sensory motor cortex, supplementary motor area, cingulate cortex, and cerebellum. Similarly a recent study (14) of cerebral cortical activity related to handgrip clearly demonstrated that the degree of striated muscle activity measured either as force or electromyographic signals is directly proportional to the amplitude of the brain signals determined by fMRI.
Findings of the present study documenting a significantly larger area of brain activity with significantly higher signal intensity during maximum compared with submaximum contraction of the external anal sphincter corroborate these previous findings and indicate that the cerebral cortical activity measured by fMRI signals is directly related to external anal sphincter contractile output.
In summary, voluntary contraction of the external anal sphincter is associated with correlated, multifocal cerebral cortical activity. These regions of activity include the primary and secondary sensory/motor cortices, the insula, as well as the association areas of the brain such as the cingulate gyrus, prefrontal cortex, and the parietooccipital region. The volume and intensity of activation of recruited cortical regions during external anal sphincter contraction is commensurate with the level of contractile effort.
![]() |
FOOTNOTES |
---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|