We briefly review the technique of functional brain imaging and its application in the assessment of the sexual response in men and women.
Magnetic resonance imaging (MRI) is a revolutionary medical imaging technique that was introduced into clinical use approximately 20 years ago. It has rapidly gained widespread acceptance because of several advantages it possesses compared with traditional medical imaging techniques, for example, X-rays, ultrasound, computed tomography and radioisotope scanning. For example, MR is exquisitely sensitive to subtle changes in tissue composition, is non-invasive and utilizes no ionizing radiation. MR is capable of providing dynamic assessment of tissue changes over time, and can also provide quantitative physiologic information such as information about three-dimensional anatomic volumes of specific anatomic structures, regional blood flow changes and information about regional metabolite composition.
Functional brain imaging (fMRI) in its most basic definition represents the ability to observe anatomic sites of brain activation in response to a specific task performed by a subject using rapid dynamic MRI. This technique is an ideal tool for exploring brain function associated with emotional attraction, feelings of pleasure and even sites of activation associated with sexual arousal and orgasm.
MRI uses radio waves and a magnetic field to generate detailed images of body tissues. It is ideally suited for brain imaging because of its ability to define different brain structures (white matter, gray matter, various nuclei) with very fine detail, compared to other imaging modalities. The magnetic field in an MRI unit causes hydrogen atoms in the body, which are magnetically polarized, to align themselves along the magnetic field lines. Radio waves agitate the atoms and tip them away from the magnetic field alignment. When this radio frequency (RF) excitation signal is turned off, the hydrogen atoms then return to their steady-state alignment, causing them to emit radio wave energy. This radio energy is then detected and measured by RF antenna coils inside the magnet bore and the resulting signals are computer processed to form an MRI image.
The strength of a magnetic field generated by an MRI magnet is measured in units called gauss (G) or tesla (T). Whereas the strength of the earth's magnetic field is approximately 1 G, the typical field strength of an MRI is 15 000 G, which is 15 kG or 1.5 T units. Most clinical brain imaging studies use 1.5–3 T machines. T1 and T2 refer to different physics properties that define how a proton relaxes and returns to its alignment along the magnetic field after it has been tipped by an RF excitation pulse. The MR images can be varied to supply different degrees of T1- or T2-weighting and this enables different tissues to appear with varying intensities. For example, on a T1 image, water appears dark, but on a T2 image, it appears bright (Figure 1).
Each MR image is a digital image that is composed of a number of picture elements or pixels. A pixel is a single, digitized ‘dot’ that has a level of whiteness or blackness that contributes to the picture. Pictures are made up of a matrix of pixels that is defined by the number of pixels on the longitudinal axis versus the number of pixels on the vertical axis. Thus, a 256 × 256 image is one that is composed of 256 rows of pixels in the vertical direction and 256 columns of pixels in the horizontal direction. The larger the number of pixels in the matrix, the higher the resolution of the image and the more detail it can provide. However, unlike digital pictures taken with a camera where a picture is a two-dimensional representation of the surfaces that reflect light, in MR each image of the brain is a ‘slice’ through the brain of a certain thickness – generally between 5 and 10 mm. Because of this slice thickness or depth of the tissue, each picture element is more often referred to as a voxel (a voxel being the three-dimensional equivalent of a pixel).
fMRI is based on the principle that when neurons become active, blood flow to them increases, and the MRI scanner is able to register this increased flow, because it results in a change in the ratio of oxygenated to deoxygenated blood in the area. Diamagnetic oxyhemoglobin affects MR signal differently than paramagnetic deoxyhemoglobin.1, 2 Although neuronal activation is accompanied by an increase in regional blood flow, a decoupling occurs between supply and utilization, as only a fraction of the oxygen in this increased flow is used to supply the increased metabolic demand imposed by the activated neurons. The result is an increase in the local tissue concentration of oxyhemoglobin, as well as a decrease in local deoxyhemoglobin concentration. This has the effect of increasing signal intensity on T2*-weighted images (T2* being a specially sensitized measure of T2 that can occur under circumstances of magnetic susceptibility disturbance) and is the basis for blood oxygen level-dependent fMRI. Thus, these local blood flow changes result in a slight change in MR signal intensity that is very subtle and is not discernable by visual inspection of a single image. However, through statistical comparison of the MR signal pattern in a set of dynamic images acquired during a resting state with those acquired during performance of a task, the area or areas of brain activation associated with that task can be identified via regional blood flow changes. Many studies have used this technique to document activation using a wide variety of motor, sensory or cognitive tasks. As the study is non-invasive and does not involve ionizing radiation, it can be repeated many times.
fMRI during sexual arousal
There have been a number of studies applying fMRI techniques to the evaluation of sexual arousal or emotional response mostly in men but also including several studies in women. Initial imaging studies analyzing the functional neuroanatomical correlates of visually evoked sexual arousal in men were performed using positron emission tomography scanning and results from these studies were first reported by Stoleru et al.3 In these studies, the brain activation response to sexually explicit video film clips was evaluated compared with emotionally neutral control film clips and humorous control film clips in ‘normal’ male subjects. This study identified for the first time the ability to define brain regions whose activation was associated with visually evoked sexual arousal in men.
Park et al.4 used fMRI together with a visual sexual stimulation paradigm similar to the design described by Stoleru et al.3 to study activation in women associated with sexual arousal. This group published the first fMRI study evaluating regions of cerebral activation associated with the female sexual arousal response. They were able to demonstrate that fMRI is also capable of showing sexual arousal response in women evoked by a visual sexual stimulus and that many of the brain activation sites overlapped with those previously described in males.
These similarities were also documented in a study by Karama et al.5 that compared the responses of men and women during viewing of erotic video film clips. They demonstrated that the levels of cerebral activation correlated with sexual arousal as measured by fMRI were significantly higher in the male subjects when compared with the female subjects. They also found that there were many similar areas of brain activation between both genders, although activation of the thalamus and hypothalamus was significantly greater in male subjects. Furthermore, the greater levels of arousal observed in male subjects were also correlated with greater levels of sexual arousal among the male subjects as reported by subjective questionnaire. Hamann et al.6 showed that although men and women showed similar brain activation patterns, activation of the amygdala and hypothalamus was more prominent in men than in women when shown the same sexual stimuli, even when women reported greater sexual arousal. They concluded that the amygdala may mediate the greater role of visual stimuli in male sexual behavior.
Our group has also studied healthy, premenopausal women without reported sexual difficulties. Analysis of the fMRI studies using two types of analyses demonstrated interesting results. The first analysis was the conventional fMRI activation analysis to define areas of increased (positive) activation associated with the sexual arousal response (Figure 2). A second analysis was conducted to evaluate for areas of the brain that showed decreased activation during sexual arousal. It was found that positive activation occurred in association with sexual arousal in many brain areas previously reported by several other groups, as expected. Analysis of areas showing decreased activation, on the other hand, revealed localized areas of decreased regional cerebral blood flow during sexual arousal in both temporal lobes, predominately in the superior and middle temporal gyri. Additionally, the areas of decreased activation on the right temporal lobe were significantly greater than those observed on the left (Figure 3). The hypothesis for this is that these areas represent sites of normally active inhibition that underwent a decrease in their level of activation during the sexual arousal response. In support of this theory, similar anatomic sites in the superior and middle temporal gyri on the right side have been associated in previous cognitive fMRI studies with embarrassment or moral judgment.7, 8
By defining normal areas of activation, one can begin to define the multiple associated cerebral components of the sexual arousal response. From these data, we can begin to construct a model of the normal cerebral sexual arousal response and the various components associated with it. Thus, these techniques show promise in eventually providing us a better understanding of previously elusive information regarding the brain components related to sexuality.
Of even greater importance, however, is the fact that these techniques may prove useful to analyze possible new methods of treatment, whether they are pharmacological treatments or psychotherapeutic approaches. For example, a study carried out by Montorsi et al.9 analyzed brain activation patterns in men during video sexual stimulation both before and following administration of apomorphine, a known proerectile mediator. The role of apomorphine in initiating the erectile process has been defined in animal models, although there have not been any direct data confirming its effectiveness in humans. The study by Montorsi et al.9 utilized sublingual apomorphine versus a placebo control agent to study 10 male patients with psychogenic arousal (erectile) dysfunction. Their responses were assessed with fMRI of the brain during visual stimulation using a video of alternating neutral and erotic content. Six volunteers with no history of erectile dysfunction served as controls. In the men with psychogenic erectile dysfunction, the sublingual apomorphine produced an increase in the extent of the activated networks of the brain plus additional activation in deep structures including the nucleus accumbens, hypothalamus and mesencephalon that was greater compared with the placebo control group. In addition, the pattern of increased responses among the apomorphine group more closely resembled the fMRI response pattern seen in control subjects without erectile dysfunction. This study demonstrates the potential utility of fMRI techniques for helping to confirm the positive response to a pharmacologic therapy as well as to define possible anatomic sites within the brain at which the pharmacologic therapy acts to produce its effect.
Finally, another area where fMRI is helping to define brain responses to sexual arousal and orgasm has been explored by Komisaruk et al.10 This group studied the brain response to vaginal-cervical self-stimulation in women with complete spinal cord injury. They found that cervical self-stimulation increased activity in the region of the nucleus of the solitary tract, which is the brain stem nucleus to which the vagus nerves project. Their findings suggest that the vagus nerve can convey genital sensory input directly to the brain in women with spinal cord injury, thus completely bypassing the injured spinal pathways.
Limitations of fMRI
There are also several limitations to the fMRI method that one should be aware of when reading the literature regarding these studies. Very small amounts of head motion, if they occur during the dynamic MR image acquisition phase of the study, can have detrimental effects on the desired result. Correct task performance by subjects must be verified – are they performing the paradigm (task) as designed or did they misunderstand the instructions or even fall asleep while lying in the magnet? Finally, paradigm design is a major consideration and must be carefully formulated when designing a study in order to produce the intended result. There are multiple phases to the sexual response: desire, arousal, orgasm, and multiple physiological occurrences during each of the phases: hormonal variation, cardiovascular changes, ejaculation and pelvic floor contractions. The brain is a very complex organ and responds in multiple different ways. Trying to isolate a specific function without interference from other tasks that may be performed simultaneously by the brain is a difficult undertaking. Ferretti et al.11 measured penile tumescence along with fMRI of brain activation to correlate different phases of the sexual response with patterns of brain activation. Further studies in a similar vein are needed to dissect out the temporal associations of central nervous system activity and peripheral/end organ responses.
Understanding of brain function associated with sexual arousal represents a truly unique and exciting application of fMRI that may enable us to unlock the mystery of the cerebral response. The hope is that such increased understanding will inevitably lead to better methods of treatment. Thus, this exciting technology promises to improve quality of life for many individuals in the coming years.
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The P300 Event-Related Potential Technique for Libido Assessment in Women with Hypoactive Sexual Desire Disorder
The Journal of Sexual Medicine (2009)