Download Brain activation during micturition in women

Brain (1998), 121, 2033–2042
Brain activation during micturition in women
Bertil F. M. Blok, Leontien M. Sturms and Gert Holstege
Department of Anatomy and Embryology, Faculty of
Medical Sciences, University of Groningen, Groningen,
The Netherlands
Correspondence to: Bertil F. M. Blok, Department of
Anatomy and Embryology, Faculty of Medical Sciences,
University of Groningen, Oostersingel 69, 9713 EZ
Groningen, The Netherlands.
E-mail: [email protected]
Summary
Experiments in the cat have led to a concept of how the
CNS controls micturition. In a previous study this concept
was tested in a PET study in male volunteers. It was
demonstrated that specific brainstem and forebrain areas
are activated during micturition. It was unfortunate that
this study did not involve women, because such results
are important for understanding urge incontinence,
which occurs more frequently in women than in men.
Therefore, a similar study was done in 18 right-handed
women, who were scanned during the following four
conditions: (i) 15 min prior to micturition (urine withholding); (ii) during micturition; (iii) 15 min after micturition; and (iv) 30 min after micturition. Of the 18
volunteers, 10 were able to micturate during scanning
and eight were not, despite trying vigorously. Micturition
appeared to be associated with significantly increased
blood flow in the right dorsal pontine tegmentum and the
right inferior frontal gyrus. Decreased blood flow was
found in the right anterior cingulate gyrus during urine
withholding. The eight volunteers who were not able to
micturate during scanning did not show significantly
increased regional cerebral blood flow in the right dorsal,
but did so in the right ventral pontine tegmentum. In the
cat this region controls the motor neurons of the pelvic
floor. In the same unsuccessful micturition group,
increased blood flow was also found in the right inferior
frontal gyrus. In all 18 volunteers, decreased blood flow
in the right anterior cingulate gyrus was found during
the period when they had to withhold their urine prior
to the micturition condition. The results suggest that in
women and in men the same specific nuclei exist in
the pontine tegmentum responsible for the control of
micturition. The results also indicate that the cortical and
pontine micturition sites are more active on the right
than on the left side.
Keywords: pontine micturition centre; M-region; pontine storage centre; L-region; anterior cingulate gyrus; inferior frontal
gyrus
Abbreviations: BA 5 Brodmann area; PAG 5 periaqueductal grey; PMC 5 pontine micturition centre; rCBF 5 regional
cerebral blood flow; SPM 5 statistical parametric mapping
Introduction
Micturition or urination is a co-ordinated action between the
urinary bladder and its external urethral sphincter. When the
bladder contracts, the sphincter relaxes. Although the motor
neuronal cell groups of both bladder and sphincter are located
in the sacral spinal cord, their co-ordination takes place in
the pons. This brainstem organization is best shown in
patients with spinal cord injuries above the sacral level. They
have great difficulty emptying the bladder, because when
their bladder contracts their urethral sphincter also contracts,
a disorder called detrusor–sphincter dyssynergia. Such
disorders never occur in patients with neurological lesions
rostral to the pons, which indicates that the co-ordinating
neurons are located in the pontine tegmentum (Blaivas, 1982).
As early as 1925, Barrington showed in the cat that the
neurons involved in the control of micturition are probably
© Oxford University Press 1998
located in the dorsolateral part of the pontine tegmentum,
because bilateral lesions in this area produced an inability to
empty the bladder, leading to urinary retention. Tracing
studies in cat (Holstege et al., 1979) and rat (Loewy et al.,
1979) revealed that a distinct cell group in the dorsal pontine
tegmentum, called Barrington’s area or the pontine micturition
centre (PMC) or M-region, projects to the sacral cord
intermediolateral cell column. Blok and Holstege (1997) have
shown that this projection is excitatory in nature and contacts
dendrites and somata of parasympathetic preganglionic
bladder motor neurons. Electrical or chemical stimulation in
the PMC produces bladder contractions (Holstege et al.,
1986; Mallory et al., 1991) and bilateral destruction of the
PMC leads to chronic urinary retention (Griffiths et al., 1990).
Another area, important during the filling phase, is located
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more ventrally and laterally in the dorsolateral pontine
tegmentum. This area, called the L-region, maintains direct
projections to the nucleus of Onuf in the sacral cord (Holstege
et al., 1979, 1986). In the cat (Sato et al., 1978; Kuzuhara
et al., 1980), monkey (Roppolo et al., 1985) and humans
(Onufrowicz, 1899; Schröder, 1981), Onuf’s nucleus contains
motor neurons innervating the pelvic floor, including the anal
and urethral sphincters. Stimulation of the L-region in the
cat results in a contraction of the pelvic floor, including the
external urethral sphincter (Holstege et al., 1986). Bilateral
lesions in the L-region cause an extreme form of ‘urge’
incontinence (Griffiths et al., 1990).
Experiments in the cat have led to a concept about the
basic micturition control systems in the CNS (Fig. 1).
Information about the degree of bladder filling is conveyed
by the pelvic nerve to neurons in the lumbosacral cord
(Morgan et al., 1981), which in turn project to the
periaqueductal grey (PAG) (Noto et al., 1991; Blok et al.,
1995; Vanderhorst et al., 1996). When the bladder is filled
to such a degree that voiding is appropriate, the PAG activates
neurons in the PMC (Blok and Holstege, 1994), which in
turn excite the sacral preganglionic parasympathetic bladder
motor neurons and inhibit the bladder sphincter motor
neurons. The bladder excitation is achieved by way of the
direct projection to the parasympathetic motor neurons (Blok
and Holstege, 1997), and the sphincter inhibition by way of
PMC projections to GABAergic interneurons in the sacral
cord dorsal grey commissure (Blok et al., 1997a; Blok and
Holstege, 1998). These GABA cells in turn project to the
motor neurons in Onuf’s nucleus (Konishi et al., 1985;
Nadelhaft et al., 1996). A recent PET study (Blok and
Holstege, 1995, 1996; Blok et al., 1997c) in healthy human
male volunteers revealed the same brainstem areas to be
associated with micturition as in the cat. The first example
is the dorsal pontine tegmentum, where the PMC is located
in the cat (see also Fukuyama et al., 1996). Other activated
areas are the midbrain PAG, the hypothalamus, the right
inferior frontal gyrus and the right anterior cingulate gyrus.
Withholding of urine, despite vigorous attempts to micturate,
was associated with increased regional cerebral blood flow
(rCBF) in the ventral pontine tegmentum, an area
corresponding to the L-region in the cat, and in the inferior
frontal gyrus and anterior cingulate gyrus, all regions on the
right side only.
PET scan studies are important for our understanding of
the micturition control system and its abnormalities. A PET
scan study on micturition in women is needed because
in women the incidence of neurogenic-related micturition
disorders is much greater than in men (Resnick et al., 1989).
In particular urge incontinence, in which a patient senses the
urge to void but is unable to delay micturition long enough
to reach a toilet, is most frequently seen in the elderly
population, mostly females (Jewett et al., 1981; Haschek,
1984; Resnick et al., 1989). Since animal studies (e.g.
Raisman and Field, 1971; Gorski et al., 1978; Breedlove,
1980) have provided ample evidence for important sex
Fig. 1 Schematic overview of pathways between spinal and
supraspinal structures involved in the control of micturition based
on experiments in cats and men. The locations of the micturition
control areas (see text) in the brainstem and diencephalon were
used in the null hypotheses for the present study in women.
Ascending (sensory-related) and descending (motor-related)
pathways are indicated on the respective left and right sides only.
BC 5 brachium conjunctivum; CA 5 anterior commissure;
IC 5 inferior colliculus; OC 5 optic chiasm; PON 5 pontine
nuclei; SC 5 superior colliculus; S2 5 second sacral segment;
(1) 5 excitatory effect; (2) 5 inhibitory effect.
differences in the structural organization of neuronal cell
groups in the CNS, the present study in women was designed
to identify the brain regions involved in micturition and to
compare the results with the PET scan findings in men, and
the anatomical and physiological findings in the cat.
Method
Experimental design
The volunteers were adult women between 20 and 51 years
of age (mean 27 years). The subjects completed a general
health questionnaire. Volunteers reporting a history of neurological, psychiatric or gastroenterological illness were
PET study on micturition in women
excluded from the study (n 5 3). The remaining 18
subjects were right-handed, and gave their written informed
consent according to the declaration of Helsinki. The
protocol of the study was approved by the research ethics
committee of the University Hospital of Groningen.
During each scan the lights were dimmed, the subjects
had their eyes closed and did not move. Each scanning
session consisted of four measurements and lasted 1.5 h
in total.
Experimental protocol and training
The volunteers were scanned during the following four
conditions: (i) filled bladder, (ii) micturition, (iii) empty
bladder and (iv) empty bladder. Eight seconds before the
second scan and 15 s after the injection of the H2150 bolus,
the right index finger of the volunteer was touched to let her
know that she could start micturition. Prior to the other three
scans no specific assignment was given. The urine was
collected with a special urological device (Femicep bedpan;
SIMS Portex Inc., Hythe, UK) attached to a plastic urine
reservoir. The device was positioned close to the urethral
orifice during all four scans. The floor of the Femicep bedpan
was equipped with a self-made battery-driven urine detector,
which, during the second condition, indicated the onset of
micturition with a small red light.
A few days before the scanning session, the volunteers
were asked to practise at home, urinating horizontally using
the Femicep bedpan. When individual practice was successful,
the PET scan session during micturition was simulated at
the subjects’ home under the guidance of one of the authors
(L.M.S.). Volunteers who were not able to micturate during
this session at home were excluded from the study. They
were asked to volunteer in a PET study on the voluntary
control of the pelvic floor musculature (Blok et al., 1997b).
About 70 min prior to the first condition of the actual
scanning session, the urine volume of the bladder was
measured with the use of an ultrasonic device, called the
Bladder Manager (Diagnostic Ultrasound Corporation,
Seattle, Wash., USA). If the Bladder Manager indicated that
the bladder was hardly filled (,250 ml) and the volunteer
affirmed that she did not have a sensation of a filled bladder,
she was asked to drink an additional glass of water. When
there was successful micturition during condition 2, the
bladder volume was measured for a second time to determine
the residual urine volume. When the bladder appeared to
contain .200 ml, the subject was asked to micturate again.
One volunteer was unable to do so, and she was catheterized
by a trained physician. Catheterization also took place in the
eight volunteers in whom micturition during condition 2 was
not successful.
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parallel to and 5 cm below the OM (orbitomeatal) line,
as determined by external examination. An individually
constructed head mould was used to prevent substantial
changes in head position. Because of the technical
characteristics of the PET camera, the most caudal limit of
the scanned area was the pons and the most rostral was the
cingulate gyrus, which meant that images were obtained from
an axial field of view of 28 mm below to 48 mm above the
intercommissural plane. This implied, for example, that
the sensorimotor cortex could not be investigated.
In order to correct for absorption of γ-radiation by
surrounding tissue, a 20-min transmission scan was made at
the beginning of the scanning session. The relative attenuation
factors, obtained from this scan, were used for correcting the
subsequent emission scans and for image reconstruction.
After the transmission scan, the subjects were given
1.85 GBq of H215O diluted in saline for each of the four
scans. The H215O bolus, followed by 40 ml saline, was
injected in the right brachial vein using an automatic
pump. Data acquisition continued for 90 s and began 23 s
after the beginning of the injection, at which time the peak
in radioactivity was assumed to have reached the cerebral
circulation. To allow the radiation to return to the background
level, there was an interval of 15 min between the injections.
Data analysis
The data of each scan were summed and the resulting images
were centred to prevent loss of information during sampling.
Prior to the statistical procedure the data were sampled to a
voxel size of 2.2 3 2.2 3 2.4 mm. The data were further
analysed using the statistical parametric mapping (SPM)
procedure (SPM95 from the Wellcome Department of
Cognitive Neurology, London, UK) implemented in Matlab
(Mathworks, Sherborn, Mass., USA) on a SPARC workstation
(Sun Microsystems, Bagshot, UK). The SPM95 software was
used for anatomical realignment, normalization, smoothing
and statistical analysis.
Realignment corrected the images for the translational and
rotational movements of the head, using the first scan as
reference. Normalizing spatial transformation matches each
scan to a reference or template, which conforms to the
stereotaxic standard space (Talairach and Tournoux, 1988).
Finally, the images were smoothed with a Gaussian filter of
8 3 8 3 8 mm3 (full width half maximum in the x, y and z
axes, respectively). This relatively small filter was used
because the main part of the study was aimed at the relatively
small brainstem and diencephalon sites that have been found
to be involved in the central control of micturition in men
(Blok et al., 1997c).
Statistical analysis
Data acquisition
The subject was placed in a horizontal position in the
PET camera (Siemens-CTI 951/31, Knoxville, Tenn., USA)
The differences in global activity within and between subjects
were removed by ANCOVA (analysis of covariance) on a
pixel-by-pixel basis with global count as the covariate. For
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B. F. M. Blok et al.
each pixel in stereotaxic space, the ANCOVA generated a
condition-specific adjusted mean rCBF value (normalized to
50 ml/dl/min) and an associated adjusted error variance. A
repeated measures ANCOVA was used for the comparison
of the four conditions.
The following contrasts for both groups were planned:
(i) scan 2 (successful/unsuccessful micturition) minus scan
3 (empty bladder), (ii) scan 2 (successful/unsuccessful
micturition) minus scan 1 (filled bladder) and (iii) scan 1
(filled bladder) minus the other conditions.
The differences between conditions were assessed by
weighting each condition with an appropriate contrast. The
significance of each contrast was assessed with a statistic
whose distribution had Student’s t distribution under the null
hypothesis. For each contrast a t statistic was computed for
every voxel to form a statistical parametric map [SPM{t};
Friston et al., 1991]. Finally, the SPM{t} was transformed
to the unit normal distribution (SPM{Z}).
Since the location of the expected micturition related areas
was predicted a priori on the basis of the PET study in males,
an uncorrected threshold of P , 0.001 was used for these
areas. Trends towards activation in the expected micturition
control areas were reported when they reached a significance
level of P , 0.005 or a Z value of 2.5. This level of
significance gives sufficient protection against false positives
(Kosslyn et al., 1994; Warburton et al., 1996).
The activation in brain areas other than those predicted to
be activated during micturition was considered statistically
significant only after correction for multiple comparisons.
This correction is necessary because, with so many voxelby-voxel comparisons, many t values will reach a
conventional level of significance by chance. The problem
was resolved by using a Bonferroni-like correction for the
number of voxels studied and reporting only those voxels
that achieved a corrected level of significance of P , 0.05
after such a correction (Friston et al., 1991).
Results
Ten of the 18 volunteers were able to micturate within 15 s
after the beginning of scan 2. The collected urine volume of
this group of volunteers was 423 6 97 ml (mean 6 SD).
One successful volunteer, who urinated 320 ml of urine
during the second scan, had to be catheterized to remove a
urine volume of 380 ml prior to scan 3. The results obtained
in this group will be referred to as ‘successful micturition’.
The other eight volunteers tried to micturate during scanning
but did not succeed (the ‘unsuccessful micturition’ group).
Of the unsuccessful micturition group, all were catheterized
(urine volume 780 6 162 ml). The data from the two groups
are reported separately.
Successful micturition group
In the 10 subjects who were able to micturate during
scanning, the sites showing significant activation (uncorrected
P , 0.001) in brain areas previously implicated in micturition
control are presented in Table 1.
During micturition (scan 2), the right dorsal pontine
tegmentum (Fig. 2, left) and the right inferior frontal gyrus
were significantly activated compared with the empty bladder
condition (scan 3). Using the same comparison, trends
towards activation (uncorrected P value between 0.001 and
0.005) were observed in the most caudal extension of the
PAG (uncorrected P , 0.002) and the rostral hypothalamus
(uncorrected P , 0.004). Other regions, previously not
implicated in micturition control, were not found to be
significantly activated (corrected P , 0.05).
Comparing the micturition condition (scan 2) with the filled
bladder condition (scan 1), increased rCBF was observed in
the right inferior frontal gyrus with micturition (Fig. 3). A
trend towards activation was found in the dorsal pontine
tegmentum (uncorrected P , 0.005). With this comparison,
other regions that have not previously been implicated in
micturition control were not found to be significantly activated
(corrected P , 0.05). The rCBF in the right anterior cingulate
gyrus (Fig. 3) was significantly decreased during the filled
bladder condition (scan 1) compared with the micturition
condition (scan 2), but also compared with the empty bladder
conditions (scans 3 and 4).
Similar significant decreases in rCBF (corrected P , 0.05)
were observed during micturition (scan 2) compared with
the other three conditions in the left medial frontal gyrus and
the right inferior frontal gyrus.
Interestingly, the right anterior insula and/or the right
frontal operculum were strongly activated (corrected P ,
0.003) during the filled bladder condition (scan 1) compared
with the empty bladder conditions, and, to a lesser degree,
compared with the micturition condition (Z score 5 4.3).
Unsuccessful micturition group
In the eight subjects who were unable to micturate during
scanning, the sites showing significant activation are
presented in Table 2. Comparing the second condition
(unsuccessful micturition; scan 2) with the condition whilst
the bladder was empty (scan 3), significantly increased rCBF
(uncorrected P , 0.001) was found in the right ventral
pontine tegmentum (Fig. 2, right) and a trend towards
significant activation (P , 0.002) in the right inferior frontal
gyrus. Comparison of the first condition (withholding of
urine) with the unsuccessful micturition condition (scan 2)
showed a significant decrease in rCBF (uncorrected P ,
0.001) in the right anterior cingulate gyrus. A similar decrease
was also found in a comparison with the empty bladder
conditions (scans 3 and 4). A trend towards significant
activation (P , 0.004) was found in the right inferior frontal
gyrus, but not in the ventral pontine tegmentum.
The ventral pontine tegmentum was also strongly activated
(corrected P , 0.05) during the filled bladder condition (scan
1) compared with the empty bladder conditions (scans 3 and
4). The right anterior insula and/or the right frontal operculum
PET study on micturition in women
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Table 1 Regional differences in cerebral blood flow during successful micturition
Coordinates of peak activation (mm)
Micturition, successful (scan 2) minus empty bladder (scan 3)
Increased rCBF
Right inferior frontal gyrus (BA 44 and 45)
Dorsal pontine tegmentum
Periaqueductal grey
Hypothalamus
Decreased rCBF
Right inferior frontal gyrus (BA 44 and 45)
Left medial frontal gyrus
Micturition, successful (scan 2) minus withholding urine (scan 1)
Increased rCBF
Right inferior frontal gyrus (BA 45 and 46)
Right anterior cingulate gyrus (BA 24 and 32)
Dorsal pontine tegmentum
Decreased rCBF
Right inferior frontal gyrus (BA 44 and 45)
Left medial frontal gyrus
Withholding urine (scan 1) minus micturition, successful (scan 2)
Increased rCBF
Right frontal operculum and/or anterior insula
Decreased rCBF
Right anterior cingulate gyrus (BA 24 and 32)
Withholding urine (scan 1) minus empty bladder (scan 3)
Increased rCBF
Right frontal operculum and/or anterior insula
Decreased rCBF
Right anterior cingulate gyrus (BA 24 and 32)
Z score
x
y
z
152
112
12
28
124
236
238
110
112
228
224
28
3.1
3.6
2.8
2.6
146
242
114
140
124
120
4.3
3.6
152
114
116
122
130
240
14
116
228
4.4*
3.6
2.5
146
242
114
140
120
120
4.7*
4.5*
138
110
18
4.3
118
138
18
3.9
138
110
112
5.1*
116
132
112
3.8
Peak activations are indicated by x, y and z coordinates according to the stereotaxic atlas of Talairach and Tournoux (1988).
BA 5 estimated Brodmann area. *Significant after multiple comparisons correction with a threshold of corrected P , 0.05.
were also strongly activated (corrected P , 0.005) during
the filled bladder condition (scan 1) compared with the empty
bladder conditions (scan 3 and 4), but not in comparison
with the unsuccessful micturition condition (scan 2).
Discussion
The present study was designed to determine the brain regions
activated during micturition in women and to compare the
results with those obtained in the previous study in men. It
appeared that the micturition-related brain regions in the
pons and cerebral cortex in men and women are the same,
and that the PAG and the hypothalamus, which have been
found to be significantly activated during micturition in men,
showed trends towards increased activation in women. It
should be stated that the axial field of view of the camera
did not involve the more superior parts of the cerebral cortex.
Areas related to micturition
Dorsal pontine tegmentum
A distinct area in the dorsal pontine tegmentum was activated
during micturition (scan 2) when compared with the empty
bladder condition (scan 3). The location of this pontine area
is similar to that of the pontine region found to be activated
in men. Since this dorsal pontine region in the cat represents
the pontine micturition centre, it seems most likely that a
similar group of neurons in the dorsal pons exists in humans
(men and women).
Right inferior frontal gyrus
The activation of the right inferior frontal gyrus during
micturition (scan 2) in comparison with a full (scan 1) or
empty bladder (scan 3) is the same in men and women,
although it is much less extensive in women. The inferior
frontal gyrus, in addition to the dorsolateral prefrontal cortex,
is involved in attention mechanisms (Pardo et al., 1991) and
response selection (Jenkins et al., 1994). With respect to
micturition, the area might play a role in deciding whether
or not micturition can take place. The observation that this
region is activated during micturition is in agreement with
specific involvement of the right prefrontal cortex in
micturition control (Kuroiwa et al., 1987; Griffiths, 1998).
Right anterior cingulate gyrus
The right anterior cingulate gyrus showed a significantly
decreased rCBF during the withholding of urine condition
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B. F. M. Blok et al.
Fig. 2 Left: significant differences in rCBF in the right dorsal pontine tegmentum (indicated by pmc 5 pontine micturition centre) after
the comparison between conditions ‘successful micturition’ (scan 2) and ‘empty bladder’ (scan 3). Right: significant differences in rCBF
in the right ventral pontine tegmentum (indicated by L-region) after the comparison between the conditions ‘unsuccessful micturition’
(scan 2) and ‘empty bladder’ (scan 3). The threshold used for display is uncorrected P , 0.005. The number 228 refers to the distance
in millimetres relative to the horizontal plane through the anterior and posterior commissures (z direction). The numbers on the colour
scale refer to the corresponding Z scores. Areas with significant activity are superimposed on averaged MRI scans (from six normal
subjects) which have been transformed stereotactically to fit a standard atlas. L 5 left side of the brain; R 5 right side.
(scan 1) compared with the successful micturition (scan 2) and
empty bladder (scans 3 and 4) conditions. This observation is
similar to that in the PET study on micturition in men.
Possibly, the decrease of rCBF in the right cingulate gyrus
during the withholding of urine results in a decrease in the
urge to void. Another argument in favour of the anterior
cingulate gyrus playing a role in micturition control is that
lesions in the forebrain have been reported to cause urge
incontinence (Andrew and Nathan, 1964; Maurice-Williams,
1974). Moreover, studies using SPECT (single photon
emission computed tomography) scanning indicate that urge
incontinence is associated with hypoperfusion of the right
forebrain (Griffiths, 1998).
Areas related to continence
Ventral pontine tegmentum
Eight of the 18 volunteers were unable to micturate when
requested, although they tried vigorously (scan 2). In this
group the ventral pontine tegmentum showed increased rCBF
during scan 2 in comparison with scan 3 (empty bladder
condition). During scan 2, the volunteers were not successful
in their attempt to micturate, probably for emotional reasons.
Despite a full bladder they contracted their urethral sphincter
and withheld their urine. The location of the activated region
in the ventral pons is similar to the region which showed
increased rCBF in the group of male volunteers, who were
also unable to micturate during scanning. In the cat this same
pontine region corresponds with the L-region, which is
involved in continence control (see Introduction).
Interestingly, this same area in the ventral pontine tegmentum
also showed strongly increased rCBF during the filled bladder
condition (scan 1) compared with the empty bladder
conditions (scans 3 and 4). Activation of the ventral pons,
including the L-region, is probably responsible for the
increased activity of the striated urethral sphincter during the
continence phase in order to keep the bladder closed. This
sphincter activity is at its highest just prior to micturition
when the bladder is filled (de Groat, 1990). However, although
in the successful group one would expect an increased rCBF
in the ventral pons during the filled bladder condition (scan 1)
compared with the empty bladder conditions (scans 3 and
4), such an increase was not found.
Right inferior frontal gyrus
The right inferior frontal gyrus was activated during
unsuccessful micturition (scan 2) in women. This result is
similar to that observed in the previous PET study in men.
The importance of the right inferior frontal gyrus in attention
mechanisms and response selection has been discussed in
the previous paragraph.
Right anterior cingulate gyrus
In a similar manner to the successful micturition group, in
the unsuccessful group the right anterior cingulate gyrus
PET study on micturition in women
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Fig. 3 Significant differences in rCBF in cortical areas after the comparison between the conditions ‘successful micturition’ (scan 2) and
‘urine withholding’ (scan 1). Note the activations in the right anterior cingulate gyrus (acg) in z planes 18 to 116, and the right inferior
frontal gyrus (gfi) in z planes 0 to 112. For other details see legend to Fig. 2.
showed decreased rCBF during scan 1 compared with the
second scan. This finding is identical to that obtained in the
PET study in men who were not able to micturate during
scanning.
Insular and opercular activation during filled
bladder condition
The right frontal operculum and/or the right anterior insula
were significantly activated (corrected for multiple
comparisons) during the filled bladder condition (scan 1)
compared with the other three conditions in the successful
micturition group, and with the empty bladder condition in
the unsuccessful micturition group. In the previous PET
study on micturition in men we did not comment on
activation related to the filled bladder condition (Blok et al.,
1997). In retrospect, unpublished results of this study
revealed that the rCBF in the right anterior insula was also
increased during the filled bladder phase (peak activation
x 5 132 mm, y 5 124 mm, z 5 112 mm; Z score 5 4.1)
compared with the empty bladder condition, which is similar
to the findings in the present study in women. However, in
men this activation was not significant for multiple
comparisons (corrected P , 0.05).
In a recent PET study (Aziz et al., 1997) the right human
anterior insula was associated with the processing of nonpainful and painful sensation from the oesophagus. Possibly,
the bladder-filling information is another example of visceral
sensation processed by the anterior insula.
Alternatively, activation of the right human insula results
in increased sympathetic tone (Oppenheimer et al., 1992).
Activation of sympathetic fibres has been shown to inhibit
mechanoreceptor discharge in the bladder wall (Vaughan and
Satchell, 1992). The result is a relaxation of the bladder wall
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B. F. M. Blok et al.
Table 2 Regional differences in cerebral blood flow during unsuccessful micturition
Coordinates of peak activation (mm)
Z score
x
y
z
Micturition, unsuccessful (scan 2) minus empty bladder (scan 3)
Increased rCBF
Right inferior frontal gyrus (BA 45)
Ventral pontine tegmentum (5 L-region)
136
18
120
222
116
228
2.8
3.8
Micturition, unsuccessful (scan 2) minus withholding urine (scan 1)
Increased rCBF
Right anterior cingulate gyrus (BA 32)
Right inferior frontal gyrus (BA 47)
116
144
136
144
116
112
3.2
2.6
136
18
122
224
112
228
5.1*
4.5*
118
134
120
3.7
Withholding urine (scan 1) minus micturition, unsuccessful (scan 3)
Increased rCBF
Right frontal operculum and/or anterior insula
Ventral pontine tegmentum (5L-region)
Decreased rCBF
Right anterior cingulate gyrus (BA 24 and 32)
For details see Table 1.
leading to increased bladder capacity. This is exactly what
happened during the first condition of the present study,
when the volunteers had a filled bladder but were not allowed
to micturate.
Predominance of the right brain in micturition
control
The micturition-related brain regions in women (frontal and
cingulate cortices) were located predominantly on the right
side of the brain, which is similar to the result of the previous
study in men. This finding corresponds with studies indicating
that urge incontinence is specifically correlated with lesions
in the right hemisphere (Maurice-Williams, 1974; Kuroiwa
et al., 1987; Griffiths, 1998). Although this right-sided
predominance was also found in the pontine tegmentum, it
should be kept in mind that, at least in cats, bilateral lesions
of the PMC are necessary to induce urinary retention.
Unilateral lesions were not sufficient to produce this effect
(Griffiths et al., 1990; Mallory et al., 1991). It is, therefore,
premature to conclude that only one side of the brain controls
micturition.
Acknowledgements
We wish to thank all the participating volunteers and members
of the Groningen PET centre involved in the micturition
project, and A. Nieuwenburg of the Department of Urology
and Dr A. M. Blok-Korenhof of the University Hospital of
Groningen for performing the catheterization. The Femicep
devices were a generous gift from Laprolan B. V. Beuningen,
The Netherlands. This research was supported by a grant
entitled ‘Neuronal control of micturition (SO-95)’ by the
Faculty of Medical Sciences of the University of Groningen.
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Accepted June 24, 1998