We focused on neuropsychologic aspect of sexual hormone, and investigated to the association of sexual hormones in basal state and brain activation during visual erotic stimulation. As our results, we found the higher plasma concentration of sexual hormones was associated with the higher brain activation by erotic visual stimulation and prolactin and testosterone might have different target region.
In our result, brain processing to visual erotic stimuli was associated with significant activation in the limbic (hippocampal-amygdalar complex) and paralimbic regions (frontal and parietal lobe, parahippocampal gyri, insula), associative cortices (temporal and occipital cortices), thalamus, midbrain, pons and cerebellum. As expected, this result is consistent to finding of the previous studies.20,23,26,27
As regards the neurobehavioral model of the brain related in sexual arousal proposed by Redouté et al.20
composed of the cognitive, emotional, motivational, and autonomic component, each component includes several areas having a same functional meaning. The cognitive component includes the frontal and parietal lobe, occipitotemporal cortex, and cerebellum. Activation of the amygdale and insula, the caudal part of the anterior cingulate gyrus and nucleus accumbens belong to the emotional component and the motivational component, respectively. Finally, the autonomic component includes the hypothalamus and the rostral part of the anterior cingulate gyrus. In the result of the current study, the visual erotic stimulation induced brain activation included all components consisting cognitive, emotional, motivational and autonomic ones proposed by Redouté et al.20
(supplementary Table 1
) This means that erotic stimuli used in our study was enough, at least, to induce attention as sexual incentives.
Our regression analysis showed that the concentration of plasma prolactin in basal state has a positive association the brain activity for the visual erotic stimulation in several regions, including left middle frontal gyrus, paracingulate/superior frontal/anterior cingulate gyri, the bilateral parietal lobule, the right cerebellum. Interestingly, these areas belong to a part of cognitive component of Redoute's neurobehavioral model of sexual arousal. Therefore, we propose that the plasma concentration of prolactin in basal state is positively correlated to the cognitive component for sexual arousal. Most of the regions overlapped with the regions positively correlated with subjective sexual desire to erotic pictures (, ). However, the negative result of the correlation analysis suggests the concentration of prolactin in basal state may not be directly related with subjective sexual desire to erotic pictures. In terms of hyperprolactinemia induced sexual dysfunction, our result, the positive correlation between prolactin and the activity of cognitive component for sexual arousal finding, may look like an inconsistent finding. Some studies, however, suggested acute or short-term elevation of prolactin might affect the facilitatory effect to sexual behavior, though the limited evidences in rat.32,33
Thus, it is considered that concentration of prolacin in our study was in the range of normal level, and duration of hyperprolactinemia, even if abnormally high level of prolactin.
The plasma concentration of testosterone in basal state showed a statistically significant positive association with the activity of the bilateral supplementary motor area (SMA) in our results. The SMA is known as a key structure for behavioral planning and execution. Both human and primates studies have reported an importance of SMA in motor tasks that demand retrieval of motor memory. The SMA appears also crucial in temporal organization of movements,34,35
and more active when performing a sequence already learned, while pre-SMA is involved in acquiring new sequences.36,37
Thus, the SMA has been suggested to be a motor-limbic interface in the transformation of emotional experiences into motor actions including erectile responses.38,39
Transforming of erotic visual inputs into the related goal-directed behavior, it is showed that the SMA may be regarded as the motivational component of Redoute's model.20
Therefore, our result suggests that testosterone in basal state associated with motivational aspect for sexual response. Our finding is consisted with previous study18
showed correlation between testosterone and sexual motivation, and might be showed this result in brain aspect with neuroimaging study.
Although the precise mechanism cannot be explained with the results of the current study, we consider possible mechanisms of prolactin in brain. The one possibility is direct effect of prolactin. The prolactin-receptor mRNA expressed on several cerebral areas suggests the possibility of the direct effect of prolactin in central nervous system.40
Several reports demonstrated that prolactin-receptor mRNA were expressed to varying degrees in the cerebral cortex as well as choroid plexus, preoptic area, mediobasal hypothalamus, amygdale, pons-medulla in both male and female rats.41,42
Although prolactin can not pass the blood-brain barrier because of its size of 199 amino acid peptide, it may reach the cortical areas through the choroid plexi. The other possibility is the indirect effect of prolactin through the dopamine system. Prolactin may feedback to dopaminergic system which is related the pleasure such as sexual behavior. An example of this feedback is the surge of release of prolactin in orgasmic state.43
If this feedback also works in basal state, the plasma concentration of prolactin may be related with the activity in dopaminergic, such as incerto-hypothalamic, mesolimbocortical or nigrostriatal, pathway44
(e.g., a person with the higher dopaminergic activity may have the higher prolactin level in basal state). The prolactin level in basal state may affect the activity of cortical region, medial frontal and anterior cingulate cortex of the cognitive component, for erotic stimulation through dopaminergic pathway such as mesolibocortical dopaminergic system which originated in the ventral tegmental area and projects to the medial limbic system including mesial frontal cortex. The association of prolactin with the brain activity in the other area of cognitive component such as middle frontal, superior parietal cortex may a secondary phenomenon which reflects the interaction between prolactin and dopaminergic activity in incerto-hypothalamic, mesolimbocortical or nigrostriatal pathway. The testosterone in basal state may also associate with the activity of SMA directly or indirectly through the interaction with dopamine in nigrostriatal or mesolibocortical pathway. However, further studies are needed to confirm the direct or indirect effect of sexual hormones such as prolactin, testosterone on a specific dopaminergic pathway and to explore the possible mechanism of the effect.
The hormones having our attention, prolactin and testosterone, have a circadian periodicity, and it might be a confounding factor in our study. Concentration of prolactin in adult men is the higher at night than the day, but it is relatively consistent in the daytime.45,46
The diurnal variation of the plasma concentration of testosterone is reported that the highest in the morning and gradually decreased across daytime in adult men.29,30
Our correlation analyses were failed to show any relationship between the scan time, corresponded to the time for blood sampling, and the plasma concentration of the two sexual hormones. To decrease of the confounding effect of the diurnal variation, the time of blood sampling for each subject should be same. In spite of the limitation of our study, our results suggested inter-subject variation of the plasma concentration of testosterone and prolactin might associate with brain activity.
Our result show no significant correlation between the plasma concentration of testosterone and subjective sexual desire raise the question whether the plasma concentration of testosterone in basal state is associated with sexual behavior. One possible reason is relatively small sample size for performing correlation analysis. Another is subjects would not report their feeling as much as they felt because they were not informed what exactly were viewed and/or their cultural background. The result of the current study showed the positive correlation of subjective feeling to erotic pictures with the brain activity of the cognitive, not emotional or motivational, component. Thus, the other is subjects would report the degree of attentional incentives, not sexual arousal or drive, as their subjective feeling.
Complex neuroendocrine system for sexual response in human might not be explained with just two sexual hormones, prolactin and testosterone. Other hormones, such as oxytocin or estrogen, and neurotransmitters, such as serotonin, norepinephrine could be related sexual behavior. Oxytocin, especially, is increased during warm social contact with the partner, such as hugging,47
and is related to monogamous pair bonding, social cognition of mating partner and sexual interaction.48
The fMRI study for maternal or romantic love showed activation of the reward system including the anterior cingulate cortex, putamen, caudate nucleus, periaqueductal gray, and substantia nigra.49
These regions coincide with areas rich in oxytocin receptors.50
These previous fMR studies suggest that oxytocin may be related with limbic area among rewarding component and/or emotional component. Further studies are needed to explore the relationship between the erotic stimulation related-brain activity and oxytocin.
Limitations of the study
In our knowledge, the current study is the first fMR study presented the association of sexual hormones in basal state with brain activity for visual erotic stimuli. However, it has a several methodological and interpretational limitations. We were not able to show a significant activation of the hypothalamus that is correlated to penile tumescence23
or sexual intensity51
to erotic stimuli, as previously reported by other fMRI studies of sexual arousal. The one possible reason is a relatively small sample size of 12 subjects. The other is that the presented erotic images might not be enough to induce the sexual arousal such as penile response. Three times repetition of the same condition block in our experimental design might be problematic if a certain brain activity sustained across the 3 blocks. This activity might not be separated from various fMR noises using high pass filter. We considered this issue. We, however, have believed the possible influence of erotic block to the subsequent happy-faced block could be more problematic than that of the repetition of the same condition block like our experimental design. Our results from the ERO minus HA contrast indicated that the induction of attention as sexual incentives was achieved with our study paradigm. In terms of diagnostic exclusion, Structured Clinical Interview for DSM-IV would be better than DSM-IV. Likert scale of 8, not 5 or 7, would affect mean score. However, the type of Likert scale may not affect the regression analyses because of their demeaned scale. Only Korean male subjects were included in the study, so this factor maybe affects the generalization of our results. Women may be show the different result from men because of the effect of estrogen on sexual behavior. Further studies might be needed to explore the relationship between sexual hormone including estrogen and brain activity in women and ethical or cultural difference in sexual behavior.
Considering the above statements and our finding, prolactin and testosterone may have a specific target regions associated with sexual response, cognitive and motivational components, respectively. Our study could be applied to explore the hormonal effect on gender difference in sexual behavior, the specific functional component of sexual dysfunction and any hormone-brain relationship using functional neuroimaging.