The Journal of Neuroscience, October 8, 2003 • 23(27):9185–9193 • 9185

Behavioral/Systems/Cognitive

Brain Activation during Human Male Ejaculation

Gert Holstege,1 Janniko R. Georgiadis,1 Anne M. J. Paans,2 Linda C. Meiners,3 Ferdinand H. C. E. van der Graaf,4 and
A. A. T. Simone Reinders5
1Department of Anatomy and Embryology, University of Groningen, 9713 AV Groningen, The Netherlands, and 2Positron Emission Tomography Centre
and Departments of 3Radiology, 4Neurology, and 5Biological Psychiatry, University Hospital Groningen, 9713 AV Groningen, The Netherlands

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron
emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation
in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer’s female partner. Primary activation was
found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding
behaviors. Parallels are drawn between ejaculation and heroin rush. Other activated mesodiencephalic structures are the midbrain lateral
central tegmental field, zona incerta, subparafascicular nucleus, and the ventroposterior, midline, and intralaminar thalamic nuclei.
Increased activation was also present in the lateral putamen and adjoining parts of the claustrum.
Neocortical activity was only found in Brodmann areas 7/40, 18, 21, 23, and 47, exclusively on the right side. On the basis of studies in
rodents, the medial preoptic area, bed nucleus of the stria terminalis, and amygdala are thought to be involved in ejaculation, but
increased rCBF was not found in any of these regions. Conversely, in the amygdala and adjacent entorhinal cortex, a decrease in activation
was observed.
Remarkably strong rCBF increases were observed in the cerebellum. These findings corroborate the recent notion that the cerebellum
plays an important role in emotional processing. The present study for the first time provides insight into which regions in the human
brain play a primary role in ejaculation, and the results might have important implications for our understanding of how human
ejaculation is brought about, and for our ability to improve sexual function and satisfaction in men.
Key words: amygdala; cerebellum; heroin; midbrain; PET (positron emission tomography); sex

Introduction tivate the MPOA and BNST. Lesions in the posterodorsal preop-
The recent success of drugs that increase male sexual perfor- tic nucleus and posterodorsal MeA in gerbils (Heeb and Yahr,
mance emphasizes the enormous impact of sexual function on 2000) resulted in a delay in ejaculation, but lesions in the sub-
the overall quality of life. Ejaculation represents a major compo- parafascicular nucleus did not. In male rats, bilateral lesions in
nent of male sexual behavior. It is the result of a coordinated the area of the LCTF completely eliminated mating behavior
action of male sexual organs such as the prostate, seminal vesicles, (Brackett and Edwards, 1984), as was the case after a unilateral
urethra, and pelvic floor muscles (Gil-Vernet et al., 1994) and is MPOA lesion combined with a lesion in the LCTF on the con-
typically accompanied by orgasmic sensations. tralateral side. Apparently, in rodents, connections between the
Studies in rats and gerbils have revealed that the medial pre- MPOA and LCTF are essential for copulation.
optic area (MPOA), medial nucleus of the amygdala (MeA), bed These studies did not elucidate the precise role of the respec-
nucleus of the stria terminalis (BNST), midbrain lateral central tive regions in sexual behavior. There are two reasons for the
tegmental field (LCTF), and parvocellular part of the subparafas- problems with determining the precise role of c-Fos in these
cicular nucleus (SPFp) express Fos activity with ejaculation events: (1) c-Fos has a temporal resolution of ⬎1 hr and, there-
(Baum and Everitt, 1992; Coolen et al., 1996; Heeb and Yahr, fore, cannot be conclusively linked to one specific event. (2)
1996). In primates, however, a decrease in c-Fos activity was There is a difference in sensitivity to c-Fos between different brain
found in the BNST and hypothalamic regions (Michael et al., structures (Kovács, 1998). The impact of lesion studies is also
1999). Baum and Everitt (1992) suggest that in rats, genital and limited, because they do not provide insight into which systems
olfactory vomeronasal input induces c-Fos activity in the LCTF/ become dysfunctional as a result of various lesions. In conclu-
SPFp and MeA, respectively, and that these regions, in turn, ac- sion, even in rodents, a complete concept regarding the sensory
and motor systems involved in ejaculation is still lacking. In other
Received May 26, 2003; revised July 16, 2003; accepted Aug. 12, 2003. species, however, almost nothing is known about the cerebral
We thank C. A. Jaspers (a member of the board of the University Hospital Groningen) and R. T. Meijer for their help organization of ejaculation.
in performing this study. We are especially indebted to members and staff of the PET and MRI centers of the With the introduction of positron emission tomography
Academic Hospital Groningen.
Correspondence should be addressed to Dr. Gert Holstege, Department of Anatomy and Embryology, University
(PET) and functional magnetic resonance imaging (fMRI) it be-
of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. E-mail: g.holstege@med.rug.nl. came possible to register and map activity in all parts of the hu-
Copyright © 2003 Society for Neuroscience 0270-6474/03/239185-09$15.00/0 man brain, including the brainstem. Several investigators have
9186 • J. Neurosci., October 8, 2003 • 23(27):9185–9193 Holstege et al. • Brain Activation during Human Male Ejaculation

Table 1. Time of ejaculation

Ejaculation 1 Ejaculation 2
Volunteer Seconds after T0 Frames Seconds after T0 Frames
1 51 5⫹6
2
3 73
4 71
5 35 3⫹4 32 3⫹4
6 74 48 4⫹5
7 55 5⫹6 60 6⫹7
8 60 6⫹7
9
10 34 3⫹4
11
Each volunteer tried to ejaculate twice (left and right column). The moment of ejaculation is measured in seconds
after tracer injection (T0), and the selected time frames are shown. When volunteers ejaculated ⬎70 sec after T0, the
corresponding time frames were not included in the present study.

studied brain activation during human sexual arousal (Stoleru et

al., 1999; Redouté et al., 2000; Bocher et al., 2001; Arnow et al.,
2002; Karama et al., 2002). The present study is the first to reveal
the brain regions in humans that are most active during
ejaculation. Figure 1. Protocol for the ejaculation condition. The bold black line shows a typical time-
activity curve. Vertical lines indicate time frames of 10 sec. Ejaculation took place within the
Materials and Methods early phase of the time-activity curve, as indicated by gray shading. kcps, Kilocounts per second.
Participants. Eleven healthy right-handed heterosexual male volunteers
(mean age, 33; range, 19 – 45) gave written informed consent according
to the Declaration of Helsinki, and the procedures were approved by the Protocol for ejaculation. The volunteers performed each of the first
Groningen University Hospital Medical Ethics Committee. None of the three tasks (rest, erection, and sexual stimulation) for 2 min, the total
volunteers had any history of physical, psychiatric, and sexual disorders. duration of a [ 15O] scan. The ejaculation task differed from the other
All volunteers, regardless of their performance, received a modest reim- three tasks in respect to its length, which, obviously, is much shorter than
bursement of travel expenses but no honorarium. 2 min (Gil-Vernet et al., 1994). To more precisely analyze the data
PET protocol. Measurements were made with an Ecat Exact HR⫹ around the actual moment of ejaculation, data acquisition was per-
(CTI/Siemens, Knoxville TN). This 32 ring PET scanner with an axial formed in multiple 10 sec frames (Silbersweig et al., 1994). For each
field of view of 15.5 cm was operated in three-dimensional mode to have ejaculation, two 10 sec frames were selected, summed, and used for sub-
maximum sensitivity of the system. A total of 63 planes were imaged sequent analysis: the time frame in which seminal expulsion, corrected
simultaneously. Spatial resolution is 4 –5 mm full-width half-maximum for a 5 sec delay between neuronal activity and regional cerebral blood
(FWHM) in all three directions. To allow for the decay of the 15O (half flow (rCBF) response (Jueptner and Weiler, 1995), took place, together
life, 122 sec), the consecutive scans were made with an interval of ⬃10 with the preceding time frame (Table 1, Fig. 1). Selection of these two
min. For each scan, 500 MBq of [ 15O] water in saline was injected into time frames approximately reflects the estimated length of human ejac-
the right median antebrachial vein and flushed with saline (total volume, ulation (Gil-Vernet et al., 1994). Because [ 15O] water diffuses into the
32 ml) at a speed of 8 ml/sec. Except for the first scan, PET scanning brain tissue most effectively during the first half of the 2 min scan, the
began 30 sec before the injection to acquire background correction in- volunteers were asked to ejaculate within the first 50 sec after the arrival
formation. After injection of the radioactive bolus, data were collected of tracer in the brain, which is ⬃20 sec after tracer injection [Silbersweig
for a duration of 2 min. A scan-specific calculated attenuation correction et al. (1993), their Fig. 1, gray area]. Eventually, 11 ejaculations were
was performed to minimize interscan displacement-induced variance obtained, of which eight were timed successfully (Table 1); these eight
(Reinders et al., 2002). were used for additional analysis.
Tasks. The volunteers were asked to perform the following tasks twice: Data processing and statistical analysis. The 1999 version of Statistical
rest, erection, sexual stimulation, and ejaculation induced by sexual stim- Parametric Mapping (SPM99) software was used for spatial transforma-
ulation. To minimize motor activity by the volunteer during the scan, tion (realignment, normalization, and spatial smoothing using an isotro-
sexual stimulation was provided by his female partner by means of man- pic Gaussian kernel of 10 mm FWHM) and statistical analysis of the data
ual penile stimulation in the tasks stimulation and ejaculation. Manual (Talairach and Tournoux, 1988; Friston et al., 1995a,b). The data were
stimulation was continued throughout ejaculation. The volunteer’s head normalized for global effects by proportional scaling (multisubject, con-
was maintained in position with a head-restraining adhesive band, and, ditions and covariates). Although in the present paper we only describe
to minimize visual input, volunteers were asked to keep their eyes closed. two of the four conditions, all four were used to estimate the variance.
In the week before the experiments, the volunteers and their female The significance of differences in rCBF is assessed using multiple univar-
partners were informed about how the experiments would be conducted, iate regression analyses. Hypothesized differences in regional cerebral
and they were asked to practice at home, especially regarding minimizing activity attributable to task-related region-specific effects can be tested by
head and limb movements. Before the experiment, the precise procedure performing a Student’s t test on each voxel of the brain using regression
was again extensively discussed with the volunteers and their female parameters. Condition-specific effects can be assessed by setting specific
partners. Great effort was made to let the volunteers feel relaxed during contrasts on the parameter estimates, testing against a null hypothesis,
the experiments. When asked for their emotional experiences during the which states that there is no difference between conditions tested. Acti-
tasks, the volunteers did not report important differences between their vations are based on the contrast ejaculation minus sexual stimulation,
sexual experience under normal circumstances and in the scanner. All and were examined at a very conservative significance threshold of p ⬍
volunteers reported to have used visual imagery to better perform the 0.01, corrected for multiple comparisons with a voxel threshold of ⱖ8.
tasks, and that stimulation and ejaculation were accompanied by plea- Significant effects are reported as z-scores (conversion of t statistics to
surable sensations. Eventually, five of them ejaculated once, three others normal distribution) in Table 2 and displayed as t statistics in the statis-
ejaculated twice, and three volunteers did not succeed (Table 1). tical parametric maps (SPMs) (see Figs. 2–7).
Holstege et al. • Brain Activation during Human Male Ejaculation J. Neurosci., October 8, 2003 • 23(27):9185–9193 • 9187

Table 2. Stereotaxic (Montreal Neurological Institute) coordinates of increases and decreases in rCBF during ejaculation compared with penile stimulation
Coordinates
Side Brain region x y z z-score
Activations
Brainstem
Right Medial pontomesencephalic tegmentum 2 ⫺28 ⫺22 5.80
Left Lateral pontine tegmentum ⫺18 ⫺14 ⫺34 6.69
Right Lateral pontine tegmentum 14 ⫺28 ⫺30 5.28
Midline Dorsal medulla (solitary complex) 0 ⫺46 ⫺50 5.48
Thalamus/midbrain
Left Mesodiencephalic junction ⫺8 ⫺24 0 7.75
Right Mesodiencephalic junction 12 ⫺24 0 6.53
Right Anterior thalamus 12 ⫺4 6 6.03
Basal ganglia
Right Claustrum/insula 34 14 ⫺8 6.21
Left Claustrum/putamen ⫺32 6 4 6.28
Right Claustrum/putamen 32 6 0 6.50
Right Putamen 20 4 8 5.38
Cortical areas
Left Inferior occipital gyrus (BA 18) ⫺2 ⫺100 ⫺4 5.20
Right Lingual gyrus (BA 18) 4 ⫺86 ⫺12 6.22
Midline Lingual gyrus (BA 18) 0 ⫺92 ⫺6 5.74
Right Precuneus/post. cingulate (BA 31/23) 16 ⫺62 24 6.38
Right Precuneus (BA 7) 8 ⫺54 50 6.05
Right Supramarginal gyrus (BA 40) 52 ⫺48 28 7.70
Right Inferior parietal lobule (BA 40) 28 ⫺38 50 5.39
Right Paracentral lobule (BA 5) 18 ⫺26 58 5.93
Right Frontal dorsal gyrus (BA 6) 16 4 60 5.88
Left Superior/medial frontal gyrus (BA 6) ⫺30 ⫺4 64 5.61
Right Superior temporal gyrus (BA 39) 54 ⫺60 36 7.05
Right Temporal operculum (BA 42) 52 ⫺28 12 6.20
Right Inferior temporal gyrus (BA 20/21) 64 ⫺6 ⫺32 6.33
Right Insula 44 14 12 5.54
Right Inferior frontal gyrus (BA 47) 54 44 ⫺12 7.03
Right Inferior frontal gyrus (BA 47) 56 38 ⫺6 6.71
Cerebellum
Left Deep cerebellar nuclei ⫺6 ⫺44 ⫺24 5.88
Left Deep cerebellar nuclei ⫺8 ⫺52 ⫺30 5.31
Left Vermis ⫺4 ⫺88 ⫺28 5.33
Right Vermis 2 ⫺58 ⫺4 6.61
Right Vermis 2 ⫺66 ⫺32 6.47
Left Hemisphere ⫺34 ⫺58 ⫺40 7.38
Left Hemisphere ⫺30 ⫺84 ⫺34 7.19
Right Hemisphere 32 ⫺68 ⫺46 6.55
Deactivations
Left Entorhinal cortex ⫺16 0 ⫺38 4.34
Left Entorhinal cortex ⫺18 10 ⫺32 3.91
Left Amygdala ⫺18 2 ⫺24 3.34
The height threshold for activations was t ⫽ 6.09 (p ⬍ 0.01; corrected for multiple comparisons) and for deactivations t ⫽ 3.21 (p ⬍ 0.001; uncorrected for multiple comparisons; extent threshold 8 voxels). Activations and deactivations
are reported in the table as z-scores (conversion of t statistics to normal distribution). After transformation to Talairach coordinates, the cortical regions were identified using the Talairach atlas (Talairach and Tournoux, 1988). The thalamic
and rostral midbrain structures were identified according to the stereotactic atlas of the human brain by Mai et al. (1997).

Deactivations were based on the contrast sexual stimulation minus Fig. 2) is based primarily on the ejaculation/orgasm and not on
ejaculation. They were examined at a significance threshold of p ⬍ 0.001 the stimulation event.
uncorrected for multiple comparisons with a voxel threshold of ⱖ8, The most intense area of activation was at the mesodience-
because at significance thresholds of p ⬍ 0.01 or p ⬍ 0.05 (corrected for
phalic transition zone (see Figs. 3, 4, 7), which encompasses sev-
multiple comparisons), deactivations were not found.
Anatomical MRIs. Individual MRIs were obtained with a 1.5 T Siemens eral structures, including the midline, ventroposterior, and in-
Vision magnetic resonance scanner and then normalized and averaged to tralaminar thalamic nuclei, subparafascicular nucleus, zona
acquire an accurate template for projection of the PET activations. This incerta, LCTF, and ventral tegmental area (VTA).
template was very similar to the mean rCBF image of all scans but was In the telencephalon, increased rCBF was observed bilaterally
preferred because of its higher resolution. in the claustrum and adjoining parts of the rostral insula as well as
Results in the striatum (ventrolateral putamen) (Fig. 5a– c). Increased
In eleven healthy right-handed heterosexual male volunteers, rCBF was also found in the anterior nucleus of the right thalamus
rCBF was measured during ejaculation and associated feelings of (Fig. 5c,d). In the neocortex, the activated regions were primarily
orgasm. Because ejaculation is a result of stimulation, we first on the right side (Fig. 6), and increased rCBF was seen in the
scanned sexual stimulation without achieving ejaculation and the inferior frontal gyrus [Brodmann area (BA) 47], in parts of the
resulting scans were compared with scans in which ejaculation parietal cortex (BA 7 and 40), and in the inferior temporal cortex
had taken place. Thus, the emerging activation pattern (Table 2, (BA 20 and 21). Increased activation was also present in the pre-
9188 • J. Neurosci., October 8, 2003 • 23(27):9185–9193 Holstege et al. • Brain Activation during Human Male Ejaculation

Figure 2. So-called glass brains for ejaculation minus stimulation. Activations are shown in a sagittal, coronal, and horizontal orientation.

Figure 3. Strong activation in the mesodiencephalic transition zone. Increased rCBF is represented in coronal sections (a– h) through the brain. The red lines on the glass brain on the left indicate
the orientation and location of the sections. Activations are superimposed on the averaged MRI of the volunteers. The activated cluster contains the VTA (sections a– d). The midline thalamic nuclei
are located slightly more caudally (sections d–f ). The lateral central tegmental field (lctf; sections c–f ) and the zona incerta are located lateral to this area. The activated region extends dorsally into
the intralaminar nuclei (intralam. nucl.; sections d– h) and the ventroposterior thalamus. Note also the activation in the medial pontine tegmentum (pt; sections g and h). y ⫽ ⫺14 (means 14 mm
posterior to the anterior commissure). r, Right side.

cuneus (BA 23/31) (Fig. 7c). In the left hemisphere (Fig. 6), in- accidents (CVAs) or Parkinson’s disease also experience sexual
creased rCBF was only found in a small portion of the superior dysfunction (Monga et al., 1986; Sakakibara et al., 2001). These
frontal gyrus (BA 6). The visual cortex (BA 18) showed increased clinical observations emphasize the importance of the brain for
rCBF bilaterally (Fig. 7b), despite the fact that the volunteers had sexual function.
their eyes closed. The brain organization of human sexual behavior is a largely
Large regions with increased activation were also seen in the unresolved matter. The techniques to investigate the brain struc-
cerebellum, including deep cerebellar nuclei, vermis, and hemi- tures involved in mating behavior, used in rats, gerbils, cats, and
spheres (Fig. 8). Of all of the cerebellar regions, the left cerebellar other animals, are not applicable to humans. Modern neuroim-
hemisphere was most heavily involved (Fig. 8f– h). aging techniques can detect brain structures that are specifically
One distinct deactivated cluster was observed. This area was in involved in ejaculation and orgasm, perhaps even better in hu-
the anterior part of the left medial temporal lobe, comprising mans than in animals. However, the spatial resolution in these
parts of the amygdala and entorhinal cortex (Fig. 9). neuroimaging techniques is much lower than most techniques
Discussion used in animals.
Clinical observations (Jochheim and Wahle, 1970) indicate that Two previous studies have attempted to register brain activa-
pathways exist between the brain or brainstem and thoracolum- tion in humans during ejaculation. An EEG study showed no
bar and/or sacral spinal cord that control sexual performance, remarkable changes in brain activity (Graber et al., 1985),
including ejaculation, because urogenital function is severely im- whereas a single positron emission computed tomography study
paired in patients with spinal cord injuries. The importance of (Tiihonen et al., 1994) indicated a decrease in blood flow in all
these pathways is also emphasized by the fact that the main com- cortical areas, except for a significant increase in the right pre-
plaint of these patients is the inability to maintain a normal sex frontal cortex.
life rather than the inability to walk (Comarr, 1971). Not only The design of the present PET study provides the time-scale
ejaculation, but also the accompanying orgasmic sensations are resolution necessary to identify brain regions that are specifically
gravely impaired or abolished in these patients (Sipski, 1998). activated during ejaculation and orgasm. Although fMRI has su-
Patients suffering from brain diseases such as cerebrovascular perior spatial and temporal resolution, we have applied PET
Holstege et al. • Brain Activation during Human Male Ejaculation J. Neurosci., October 8, 2003 • 23(27):9185–9193 • 9189

Figure 4. Increased rCBF is represented in oblique (45°) sections (a– d) through the brain, to enable comparisons with sections obtained in experimental animals. The red lines on the glass brain
on the left indicate the orientation and location of the sections. Activations are superimposed on the averaged MRI of the volunteers. The activated cluster contains the VTA (sections a– d). r, Right side.

Figure 5. Activations in the basal ganglia and the anterior nucleus of the thalamus and absence of activation in the hypothalamus. Increases in rCBF are superimposed on the averaged MRI of the
volunteers and are depicted in coronal sections (see the red lines on the glass brain on the left). Activations are found in the lateral putamen and perhaps the laterally adjoining claustrum and insula
(cp; sections a– c). Note that in sections c and d, the anterior nucleus (na) of the thalamus is on the right side. Sections (b-d) demonstrate that in the hypothalamus (hyp) no activation is found. y ⫽
⫺6 (means 6 mm posterior to the anterior commissure). r, Right side.

cocaine (Breiter et al., 1997) and heroin

rush (Sell et al., 1999). The finding that
heroin addicts experience orgasmic plea-
sure with heroin usage (De Leon and Wex-
ler, 1973; Mirin et al., 1980; Seecof and
Tennant, 1986) fits with the notion that the
VTA is the key element in both heroin and
sexual orgasm. It also may explain why
heroin addicts have a suppressed sex drive
(Minz et al., 1974; Cicero et al., 1975), be-
cause heroin already heavily stimulates this
region (Sell et al., 1999). The present find-
Figure 6. Activations in the cerebral cortex rendered onto a standard anatomical template (SPM99). Note that the cortical ings may represent an anatomical sub-
activations are almost exclusively on the right side. strate for the strongly reinforcing nature of
sexual activity in humans. Because ejacula-
tion introduces sperm into the female re-
scanning, because it is less sensitive to movement artifacts than productive tract, it would be critical for reproduction of the spe-
fMRI (Turner et al., 1998). The various regions in which in- cies to favor ejaculation as a most rewarding behavior.
creased rCBF was found will be discussed successively. Another candidate for involvement in ejaculation is the dopa-
minergic A11 cell group, which is also located within the acti-
Mesodiencephalic junction vated region in the mesodiencephalic transition zone (Pearson et
The strongest activation was found in the mesodiencephalic tran- al., 1990). The A11 cell group in rats (Skagerberg and Lindvall,
sition zone. On the basis of the limited spatial resolution of the 1985; Holstege et al., 1996), cats, and monkeys (Holstege et al.,
PET technique, it is not possible to distinguish specific brainre- 1996) maintains direct projections to all parts of the gray matter
gions within this area. The activated area at the mesodiencephalic throughout the length of the spinal cord, but its strongest projec-
junction comprises the VTA, subparafascicular nucleus, LCTF, tions are to the pelvic floor motoneurons in the upper sacral cord,
and medial and ventral thalamus. the cremaster motoneurons in the L2 or L3 segments, and the
The VTA is located ventrally in the activated cluster. It con- T1-L2/3 sympathetic preganglionic motoneurons, including
tains the A10 dopaminergic cell group and plays a crucial role in those innervating the genital organs.
a wide range of rewarding behaviors (McBride et al., 1999). In- An additional region that might play a role in ejaculation is the
creased activation in the area of the VTA was also seen during LCTF. In male rats, in which the LCTF comprises the SPFp, it is
9190 • J. Neurosci., October 8, 2003 • 23(27):9185–9193 Holstege et al. • Brain Activation during Human Male Ejaculation

Figure 7. Sagittal view of the activations in midline cortical structures, the mesodiencephalic transition zone, and the cerebellum. Increased rCBF is represented in sagittal sections, of which the
location is indicated by the red lines on the glass brain on the left. Activations are superimposed on the averaged MRI of the volunteers. In b and c, activation in the secondary visual cortex (BA 18)
and posterior cingulate/precuneus (BA 23/31), respectively, can be found. Note in sections a– c that the activation in the mesodiencephalic transition zone (mes-di) extends from the rostral midbrain
into the ventral parts of the caudal thalamus. x ⫽ ⫺12 (means 12 mm left to the intercommissural line).

Figure8. Activationsinthecerebellum,brainstem,andoccipitalcerebralcortex.IncreasesinrCBFaresuperimposedontheaveragedMRIofthevolunteersandaredepictedinoblique(45°)sections(seethe
red lines on the glass brain on the left). Cerebellar activations can be observed in the vermis (v; sections b– h), the cerebellar hemispheres (ch; sections d– h), and the deep cerebellar nuclei (dcn; sections b– d).
Note that activation in the cerebellar hemisphere is more pronounced on the left than on the right side. Brainstem activation is present in the medial pontine tegmentum (section a), the lateral pontine
tegmentum (sections b and c), and in a region possibly involving the dorsal vagal nuclei and the solitary complex (sections f and g). pt, Pontine tegmentum; r, right side.

Figure 9. Deactivation in the anterior part of the left medial temporal lobe, comprising parts of the amygdala and entorhinal cortex (entorhin.). Decreases in rCBF are superimposed on the
averaged MRI of the volunteers and are depicted in coronal sections (see the red lines on the glass brain on the left). The significance threshold was p ⬍ 0.001 (uncorrected for multiple comparisons).
y ⫽ ⫺2 (means 2 mm caudal to the anterior commissure).

known to contain c-Fos-immunoreactive neurons after ejacula- lumbar segments has been shown to send fibers through the spi-
tion (Baum and Everitt, 1992; Coolen et al., 1996). Lesions of the nal cord and brainstem to terminate in the LCTF/SPFp (Truitt et
LCTF/SPFp have been reported to disrupt ejaculatory behavior in al., 2003). Ablation of these neurons by the selective toxin [Sar9,
rats (Brackett and Edwards, 1984). The present results further Met (O2) 11 substance p]-saporin resulted in complete disrup-
corroborate the importance of the LCTF/SPFp in ejaculation. In tion of ejaculatory behavior, while other components of sexual
rats, a galanin-containing group of cells in the third and fourth behavior remained intact (Truitt and Coolen, 2002).
Holstege et al. • Brain Activation during Human Male Ejaculation J. Neurosci., October 8, 2003 • 23(27):9185–9193 • 9191

The pattern of thalamic activation might include both the (Fig. 5c). In rodents, the MPOA is considered critical for sexual
midline and intralaminar nuclei, as well as the ventral part of the behavior, because rat studies (Hansen et al., 1982; Brackett and
ventroposterior nuclei. The midline and intralaminar nuclei have Edwards, 1984; Baum and Everitt, 1992) suggest that it plays an
been associated with generalized arousal (Kinomura et al., 1996), important role in arousal and ejaculation. In primates, however,
and the outer or “shell” portion of the ventroposterior thalamic none of these regions show increased c-Fos in males that ejacu-
nuclei has been associated primarily with visceral sensory re- lated compared with unmated males (Michael et al., 1999). Our
sponses (Bruggeman et al., 1994). Thus, the activation of the data support the latter findings. Perhaps in primates the MPOA is
thalamus during ejaculation might reflect both the sensory expe- not involved in ejaculation but plays a role in creating the proper
rience as well as its arousing aspects. conditions for sexual behavior.

Striatum and cerebral cortex

Deactivations in amygdala and entorhinal cortex
Strong activation in the lateral putamen and adjoining claustrum
and insula, very similar to the present study, was found to be The only cluster of deactivation that could be found was in parts
correlated with male sexual arousal (Redouté et al., 2000) and of the amygdala and entorhinal cortex (Fig. 9), albeit at a thresh-
penile turgidity (Redouté et al., 2000; Arnow et al., 2002). The old of p ⬍ 0.001 (uncorrected for multiple comparisons). From
intense activation of the parietal lobe (BA 7 and 40) on the right rodents to primates, the amygdala is well known for its role in
side has been reported previously during sensory stimulation and vigilance and fear. Neuroimaging experiments have confirmed
may represent attention to the body surfaces that are being con- these observations in humans by demonstrating increased amyg-
tacted (Coghill et al., 2001). dala activation by fearful stimuli (for review, see Davis and
Activation of the precuneus (BA 31) may be related to the Whalen, 2002; Rauch et al., 2003). Our results correspond with
visual imagery that the volunteers used, because this region has the finding of Redouté et al. (2000), who found that the medial
been associated with memory-related imagery (Fletcher et al., temporal lobe showed a negative correlation with penile tumes-
1995). The prefrontal activation (BA 47) on the right side was also cence and sexual arousal. In other neuroimaging studies, de-
found in successful micturition (Blok et al., 1997, 1998). Perhaps creased amygdala activity was found when volunteers who were
this part of Brodmann area 47 is the urogenital part of the pre- deeply in love viewed pictures of their loved ones (Bartels and
frontal cortex, which plays a role in deciding whether or not Zeki, 2002). Breiter et al. (1997) showed a similar deactivation
micturition or ejaculation occurs at a particular time and place. when volunteers experienced cocaine rush, and they suggested
The finding that the cortical activations are found almost exclu- that amygdala deactivation correlates with euphoric psychologi-
sively on the right side corresponds with the results of Coslett and cal states. The orgasmic experience during ejaculation in the
Heilman (1986), who reported that the frequency of sexual dys- present study might also be considered as an example of such
function is significantly higher after CVAs in the right than in the euphoric states.
left hemisphere.
At first glance, the activation of the secondary visual cortex
(BA 18) seems surprising, because the volunteers had their eyes Epilogue
closed. This activation might be explained, however, by the vol- Understanding the inter-relationships of the neuronal popula-
unteers using visual imagery during the experiments. BA 18 is tions that are activated during ejaculation will provide an impor-
reported to be activated during visual hallucinations also (Silber- tant challenge for future studies. The recent enormous success of
sweig et al., 1995). sexual potency-increasing drugs is a reflection of the magnitude
of problems in the field of sexual health. To confront problems
Cerebellum such as impotence and premature ejaculation, it is crucial to un-
Most prominent activation was found in large portions of the derstand how the human brain controls penile erection, sexual
cerebellum during ejaculation. It is possible that this activity rep- arousal, and ejaculation. The present study for the first time re-
resents movements made by the volunteers during ejaculation, veals brain regions involved in human male ejaculation and or-
although these movements were relatively limited. The cerebel- gasm. We expect that future studies will disclose more precisely
lum, however, is not only involved in motor but also in emotional the role of these structures and the neurotransmitters and neuro-
processing (Middleton and Strick, 2000). Our results correspond modulators that are involved. The results will have important
with reports of cerebellar activation during heroin rush (Sell et implications for our ability to influence these specific brain re-
al., 1999), sexual arousal (Redouté et al., 2000), listening to plea- gions, to improve sexual function and satisfaction in men.
surable music (Blood and Zatorre, 2001), and monetary reward
(Martin-Sölch et al., 2001). Moreover, clinical studies have re-
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