Central mechanisms of ejaculatory dysfunction: a multi-modal fMRI investigation

Extremes in the duration of the intravaginal ejaculation latency time (IELT)
may give rise to subjective complaints of ejaculatory dysfunction, e.g.
premature ejaculation (PE) or retarded ejaculation (RE). These problems are
prevalent in the male population, and cause considerable distress. Given the
well-established link between men*s sexual and general health, and in
consideration of the fact that sexual health may be an important contributor to
healthy ageing, it would be important to get to the heart of sexual
dysfunctions like those that affect ejaculatory/climacteric behaviors.

The brain is the primary suspect in ejaculatory problems as the genitalia seem
to function normally in these conditions. Experimental neurobiological
investigations in rodent models have focused heavily on subcortical circuitry
as the primary mediator of the IELT, but this may only partly be relevant for
the human situation where the role of phylogenetically more recently developed
brain structures, like the cerebral cortex, is likely to be important for the
control of sexual behavior. Critically, we have highly promising pilot fMRI
data suggesting that the integrity of the corticospinal tract close to the
genital/pelvic part of the primary sensorymotor cortex may modulate the human
IELT. In this project, we will therefore look more closely at the higher brain
mechanisms that control the IELT.

Our planned research is very relevant in the field of sexual medicine. Current
treatment strategies for ejaculatory dysfunction, like anti-depressants, are
suboptimal, and the treatment regime is not always tolerated because of adverse
side-effects.

The aim of the proposed research is to assess, using multimodal fMRI, both
functional (BOLD responses) and structural (white matter) cerebral
characteristics of the human IELT. In turn, this could provide specific novel
(neocortical) targets in the brain, , through which treatment could be refined.
The latter is important as ejaculatory dysfunctions are often treated with
anti-depressants, which may have considerable side effects.

The research we propose is minimally invasive observational research. It
consists of two stages:
Stage 1 is a thorough sexual medical assessment/screening, including filling
out questionnaires, giving blood and saliva, and an interview with a
sexologist.

Stage 2 is an fMRI experiment aimed at uncovering both structural and
functional central characteristics of the IELT. In the functional part of the
fMRI experiment subjects will receive (non-erotic) penis stimulation and will
be asked to contract their pelvic floor muscles. The structural scans will not
involve any task. The male subject's female partner will perform the necessary
penis stimulations.

The intervention entails mild stimulation of the glans penis. Stimulation will
occur in a standardized way, and is not aimed to induce feelings of sexual
arousal in he subject. Stimulations will be executed by the female partners of
the subjects.

Most subjects will pay two visits to the UMCG. The first visit, the sexual
medical assessment, will take about one hour. Subjects give a small amount
blood, which may be slightly uncomfortable.

The second visit is for the fMRI experiment. Subjects will be exposed to a
magnetic field of 3 Tesla and rapidly alternating magnet gradients and radio
frequency fields. This field strength is used on a routinely basis in fMRI and
MRI research. So far, no side effects have been described. On rare occasions, a
peripheral nerve (abdomen) is stimulated by the changing magnet gradients. This
will cause an itching feeling, but it is not harmful. Therefore, the
participating subjects will have minimal to negligible burden due to the nature
of the study itself (e.g. staying in the scanner for an hour). Including
questionnaires that should be filled in prior to the experiment, and a
post-fMRI psychological task, the total duration of the second visit will
amount to approximately two hours.

Female partners only participate in the fMRI experiment, that is, they assist
in the fMRI task (penis stimulation).