Brain activation by visual erotic stimuli in healthy middle aged males (2006)

Abstract

The objective of the present study was to identify brain centers, whose activity changes are related to erotic visual stimuli in healthy, heterosexual, middle aged males. Ten heterosexual, right-handed males with normal sexual function were entered into the present study (mean age 52 years, range 46-55). All potential subjects were screened over 1 h interview, and were encouraged to fill out questionnaires including the Brief Male Sexual Function Inventory. All subjects with a history of sexual arousal disorder or erectile dysfunction were excluded.

We performed functional brain magnetic resonance imaging (fMRI) in male volunteers when an alternatively combined erotic and nonerotic film was played for 14 min and 9 s. The major areas of activation associated with sexual arousal to visual stimuli were occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, caudate nucleus.

However, hypothalamus and thalamus were not activated. We suggest that the nonactivation of hypothalamus and thalamus in middle aged males may be responsible for the lesser physiological arousal in response to the erotic visual stimuli.

Introduction

With the development of the functional imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), the knowledge for brain substrate for the sexual response is accumulating.^{1, 2} Park et al.³ had investigated relationships between brain activation and sexual response in 12 young males (mean age=23 years) with normal sexual function. They reported that the activated brain areas by erotic visual stimuli were inferior frontal lobe, cingulate gyrus, insula, corpus callosum, caudate nucleus, globus pallidus, inferior temporal lobe, and thalamus. Arnow et al.² developed an experimental paradigm including an objective measure of tumescence and erotic visual stimuli, as well as neutral and visually stimulating control segments using fMRI technology to evaluate regional brain activation during sexual arousal. The major areas of activation associated with tumescence were right insula/subinsular region, including the claustrum, caudate nucleus, putamen, cingulate gyrus, occipito-temporal area, and hypothalamus. A study compared gender differences in sexual stimuli showed that only for the male subjects had a significant activation of hypothalamus.⁴ Although the understanding for the brain substrate for sexual arousal has been much increased like these studies, subject of all studies were limited into young adults. Since the sexual dysfunction is very prevalent in older male than younger ones, it should be elucidated the aging-related changes of brain activation by sexual stimuli.⁵ To identify brain regions where functional perturbations disrupt the regulation of sexual arousal in patients with sexual arousal disorders, a study that is exploring the brain activation in the middle aged males would be needed.

The objective of the present study was to identify brain centers, whose activity changes are related to erotic visual stimuli in healthy, heterosexual middle aged males. Comparing with the findings reported in the functional neuroimaging studies in young males, different brain activation profiles would be expected.^{2, 3, 4}

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Methods

Subjects

Ten heterosexual, right handed males with normal sexual function were entered into the present study (mean age 52 years, range 46–55). All potential subjects were screened over 1-h interview, and were encouraged to fill out questionnaires including the Brief Male Sexual Function Inventory (Table 1).⁶

Table 1 – Brief male sexual function inventory.

Full table

The absence of physical disorders and of any pharmacological treatment was checked through a medical examination. The study design was explained in detail and the selected subjects read and signed informed consent before entering the study. All subjects with a history of sexual arousal disorder or erectile dysfunction were excluded. The study protocol was approved by the institutional review board at St. Mary’s Hospital, The Catholic University of Korea.

Activation stimuli and MRI image acquisition

We presented to the subjects a film clip, which lasted for 14 min and 9 s. This clip consisted of alternating segments of relaxing scenes (R), sports highlights (S) or sexually arousing erotic scenes (E) in the following order: S, R, E, R, E, R, S, R, S, R and E. The respective times for these segments in seconds were: 129, 60, 120, 30, 120, 30, 120, 30, 60, 30 and 120 (s). A number of considerations informed the design and specific stimuli. Given data suggesting that subject disengagement from emotionally stimulating visual material under fMRI conditions takes approximately 15 s, the S and E segments were not contiguous and were separated by a minimum of 30 s of R.⁷ The content of the erotic segments involved four types of sexual activities: rear-entry intercourse, intercourse with the female in the superior position, fellatio, and sexual intercourse with the male in the superior position. Of eight different sexual activity-depicted films, these four activities were associated with the highest level of perceived sexual arousal and penile erection in a sample of 40 healthy males. Finally, in order to control possible anticipation effect, subjects were not informed of the ordering of segments.

During fMRI sessions, the film clips were presented to the subjects through a mirror located at the top of the head coil that receives video-images from outside of the magnetic room. Echoplanar images (EPI) were acquired on 1.5 T MRI system (Magentom Vision Plus, Siemens, Erlangen, Germany). Thirty slices (5 mm thick) were acquired every 3.106 s in an inclined axial plane, aligned with the AC-PC axis. These T2-weighted functional images were acquired using an EPI pulse sequence (TR=0.6 ms, TE=60 ms, Flip 90, FOV=240 mm, Matrix=64 64). After functional scanning, high-resolution data were acquired via a T1-weighted 3D volume acquisition obtained using a gradient echo pulse sequence (TR=9.7 ms, TE=4 ms, Flip=12, FOV=240 mm, Matrix=200 256).

Data were analyzed using Statistical Parametric Mapping (SPM99, Wellcome Department of Cognitive Neurology, London, UK). Scans were realigned and spatially normalized using the standard Montreal Neurological Institute (MNI) template. Images were then convolved in space with a 3D isotopic Gaussian kernel (full-width at half-maximum, FWHM, of 8 mm) to improve the signal-to-noise ratio and to accommodate for residual variations in functional neuroantomy that usually persist between subjects after spatial normalization. Effects at each and every voxel were estimated using the general linear model. Voxel values for each contrast yielded a statistical parametric map of the t statistic (SPMt), subsequently transformed to the unit normal distribution, SPM{Z}. A ‘random-effects model’ was implemented to produce the E (erotica) minus N (neutral) contrasts. This model is implemented within SPM99 using a multi-stage approach.

The hypothalamus, thalamus, anterior cingulate gyrus, occipitotemporal cortex, anterior temporal cortex, parietal cortex, amygdala, hippocampal formation, orbitofrontal cortex, ventral striatum, the claustrum, the nucleus accumbens, the parietal lobules have all been shown to respond to sexually explicit films in male subjects.^{2, 3, 4, 8} For each of the brain areas mentioned above, a set of coordinates was calculated by taking the average for each orthogonal axis X, Y and Z of reported Talairach coordinates.⁹ Predetermined regions of interest (ROI) were limited by spheres having a radius of 9 mm and for center, the calculated average reported coordinates. For these priori ROIs, height threshold was set at P<0.001 (z=3.09), uncorrected for multiple comparisons. For other brain areas, height threshold was set at P<0.05, corrected for multiple comparison.

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Results

When the blood oxygen level dependent (BOLD) activity associated with viewing the emotionally neutral film segment (S) was subtracted from that associated with viewing the erotic segment (E), significant (P<0001, uncorrected) loci of activation are listed in Table 2 and illustrated in Figures 1 and 2. The major areas of activation associated with sexual arousal to visual stimuli were occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, caudate nucleus. However, hypothalamus and thalamus were not activated.

Figure 1.

Brain areas whose activation was related to erotic-visual stimuli in healthy middle aged male subjects (pooled group data, N=10).

Full figure and legend (162K)

Figure 2.

Axial view of activated brain areas by erotic visual stimuli in healthy middle aged male subjects (pooled group data, N=10).

Full figure and legend (355K)

Table 2 – Brain regions with a differential activity in response to sexually explicit and emotionally neutral visual stimuli in healthy middle aged male subjects (pooled group data, N=10).

Full table

Discussion

It has been proposed that human sexual arousal, which is usually triggered by external stimuli or endogenous factors, is a multidimensional experience comprised of four closely interrelated and coordinate component: cognitive, emotional, motivational, and physiological.^{8, 10}

In the present study, the major areas of activation associated with sexual arousal to visual stimuli were occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, caudate nucleus. However, hypothalamus and thalamus were not activated. Activation of the occipitotemporal area accords with results of recent functional study, in which emotionally laden visual stimuli elicited increased activation in this cortical region.^{11, 12} Reiman et al.¹³ provided some evidence that the anterior cingulate gyrus is involved in the conscious experience of emotion. In functional neuroimaging study, the activation of anterior cingulate gyrus was highly correlated with the levels of perceived sexual arousal, which were related to the perceived urge to perform sexual actions.⁸ These results have been replicated in following studies using fMRI.^{2, 3, 4} Orbitofrontal cortex has been shown to be implicated in the representation of rewards.¹⁴ Redoute et al.⁸ suggested that the orbitofrontal activation noted in their PET study might have been related to the representation of the pleasant bodily sensations induced by penile tumescence.

In the present study, the thalamus and hypothalamus were not activated. The afferent stimuli are routed to the cortex via the thalamus that regulates the flow of sensory information. Interestingly, the thalamus represents a hub from which any area in the cortex can communicate with any other brain regions. This extensive thalamocortical inter-connectivity has been theorized to constitute a neural basis for conscious awareness.¹⁵ If this hypothesis were correct, the thalamus would be implicated in the cognitive dimension of sexual arousal. One of the major thalamocortical interconnections is cortico-striato-thalamo-cortical curcuit. Projections from the orbitofrontal cortex via the caudate nucleus, both of which are considered as inhibitory systems, is thought to mediate context-related operations and response inhibition.¹⁶ In light of such a view, the non-activation of thalamus, and activation of orbitofrontal cortex and caudate nucleus in this study might suggest that middle aged males be more inhibited by thalamocortical interconnection and then less aroused to the visual sexual stimuli than young ones. A large number of studies have linked the hypothalamus to sexual response. Neuroanatomically, lesions in the medial preoptic area of the hypothalamus impair male copulatory behavior in all species tested,¹⁷ and electrical stimulation of the paraventricular nucleus of the hypothalamus is associated with erection in rats.¹⁸ In addition, neurochemically, direct injection of apomorphine, dopamine agonist, into the paraventricular nucleus stimulates erections in the rats.¹⁹ Redoute et al.⁸ demonstrated a correlation between activation in the hypothalamus and measures of penile tumescence in the PET study. Arnow et al.² also reported similar results in the fMRI study. Interestingly, Karama et al.⁴ reported that the hypothalamus was less activated in female than in male in response to visual sexual stimuli, and suggested that female subjects were physiologically less aroused than male subjects. Yang²⁰ examined the brain activation to the visual sexual stimuli in depressed patients with sexual dysfunction, and reported that hypothalamus and thalamus were less activated than normal control group. Based on the results mentioned above, hypothalamic nonactivation in this study for the middle aged males suggests that these subjects were physiologically less aroused in response to the erotic visual stimuli. Although evidences for such inhibitory mechanisms over hypothalamus has been largely indirect and has received much less attention than excitatory mechanisms, a recent attempt to locate the specifically sexual inhibitory effects of serotonin does have an inhibitory role in the lateral hypothalamic area.²¹ This is consistent with the well-established inhibitory effects of specific serotonin re-uptake inhibitors (SSRIs) on sexual response.²²

Considering extensive inter-connectivity of the brain, and ‘dual control’ model over sexual response, one of the mechanisms of the nonactivation in the thalamus and hypothalamus, which are known as primitive center for sexual arousal could be exaggerated inhibition of the inhibitory system.

Regarding the limitations of the study, it should firstly be noted that we had studied only middle aged males and young control group were not included. Since our study design, (e.g. the lasting time of erotic and neutral film segments) was very similar to the previous works for the young ones, it would be possible to compare each others indirectly.^{2, 4} However, to control the variability of functional imaging research, the comparison study for middle aged and young adults at the same time should be needed. Secondly, we could not demonstrate directly the inter-connectivity of particular brain regions involving excitatory and inhibitory system. Thus, our interpretations should be considered as a hypothesis to be tested in the future more direct study focused on these brain circuitry. Another limitation concerns the lack of objective measures of the sexual arousal such as penile tumescence.

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Conclusions

We have identified by using fMRI, for the first time, the functional neuroanatomy of the brain associated with sexual arousal in middle aged males. The result was the activation of occipitotemporal gyrus, anterior cingulate gyrus, orbitofrontal cortex, and nonactivation of hypothalamus and thalamus. We suggest that the nonactivation of hypothalamus and thalamus in middle aged males may be responsible for the lesser physiological arousal in response to the erotic visual stimuli.

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Acknowledgements

This work was supported by Grant No. R01-2003-000-10432-0 from the Basic Research Program of the Korea Science & Engineering Foundation.