3. Investigation of the Central Nervous System in Neurogenic Pelvic Dysfunctions by Imaging
KeywordsBladderBrain imagingfMRIMicturition controlSuprapontine
Several suprapontine structures contribute to the functional control of the pelvic organs, of micturition, defecation, continence and sexual function. They are coordinated in complex networks that are able to adapt themselves to altered conditions.
Damage to those suprapontine structures provokes basically a limited number of different clinical conditions: retention, incontinence, urgency and sexual dysfunction.
On the other hand, these clinical conditions themselves may cause functional modifications of the suprapontine structures as long as at least some connectivity with the cerebral structures is upheld. Psychological distress may contribute to the onset of an overactive bladder .
It is unclear to which point neurogenic pelvic dysfunctions are direct consequences of the damage of a defined structure or whether they are the sum of interdependent phenomena.
Therefore, it could be hypothesized that the recovery of neurogenic pelvic dysfunctions depends not only on the healing process of the CNS itself, but also on the way the involved areas as well as the pelvic organs will react and interact.
The conventional MRI and CT scan-based diagnosis of the damage of a cerebral area may well give hints about a possible subsequent neurogenic pelvic dysfunction—but only up to a certain degree.
The last two decades have seen a dramatic evolution of new techniques to investigate brain function. Actually, they may still have a limited clinical applicability in daily activity and only a limited number of algorithms of their use exist. Nevertheless, in the same way that the introduction of the PSA has boosted the development of the therapy of prostate cancer, it is to be expected that more sophisticated diagnostics will lead to a more efficient and punctual, a more tolerable and cheaper management of patients with neurogenic pelvic dysfunctions.
The goal of this chapter is to provide an introduction to the techniques of investigation of the suprapontine structures and to the evolution of the knowledge they have created.
3.2 What Do We Know About Methodology?
Conventional CT and MRI scans may correlate the site of cerebral lesions with the probability of the presence of a certain type of pelvic dysfunctions . Functional brain imaging, instead, provides information about the activation of brain areas in relation to physiological body functions and pathological conditions.
The major part of the contributions in this field derives from investigations with four techniques: single-photon emission computerized tomography (SPECT), positron-emission tomography (PET), near-infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI).
All these methods of functional brain imaging rely on the principle that an increase in neuronal activity requires an increase of blood supply [3, 4].
SPECT and PET are two nuclear medicine techniques, which may demonstrate cerebral activity through the accumulation of radioactive substances.
SPECT detects γ-rays emitted by photons. It has a limited temporal and spatial resolution of 10 mm, but it has a lower cost compared to PET.
In PET high-energy photons are produced by the annihilation of the positron-emitting isotopes. The spatial resolution is about 5 mm.
Given that in both nuclear medicine techniques a radioactive substance has to be injected prior to the investigation, they are considered invasive.
NIRS and fMRI rely on the fact that oxygenated and deoxygenated haemoglobin have different physical proprieties. While NIRS signal depends on the fact that oxygenated and deoxygenated haemoglobin have different absorption spectra, fMRI signal basically reflects its different paramagnetic proprieties. Therefore, both techniques are non-invasive.
While NIRS has the lowest spatial resolution (30 mm), its big advantages consist of a high temporal resolution, its low costs and not requiring a strict motion limitation [5, 6].
fMRI has surely established itself as the most feasible, basically given to it being non-invasive and free of radiation. Anyway, even if the last 20 years have seen an explosion of fMRI-based brain imaging studies, this methodology has at least two major limits—to some degree shared with the other techniques.
An intrinsic one lies on the fact that brain structure and circuitry pose a limit on how good fMRI signal can be interpreted. As Logothetis  has pointed out, the fMRI signal cannot either be easily differentiated or be easily quantified in its magnitude. In other words, a clear unidirectional discrimination between function-specific processing and neuromodulation, bottom-up and top-down signals, excitation and inhibition as well as brain region activation is not always possible.
A further limit consists of the high variability (if not fragmentation) of the investigation protocols used. Limited consensus exists about the tasks used to investigate brain activity during bladder filling, voiding or urge, while an investigation protocol about voiding in an ecological situation has been defined only few years ago. Procedures may vary according to how fast the bladder is filled, whether and in which position subjects are allowed to void, whether they have to contract or relax the pelvic floor muscle or whether they have to try to suppress urgency, to name a few.
A strong theory about brain function not the data in themselves explains the phenomena observed.
Only an integration of data and knowledge coming from different investigative methods (not least anatomical and in vivo studies) can shed light on brain function.
3.3 What Do We Know About the Central Control of Micturition in Healthy Subjects?
3.3.1 Systematizing the Knowledge About Brain and Bladder
In the last decades a growing interest in the investigation of the central control of bladder and micturition has led to many experimental studies as well as many reviews, the latter systematizing the accumulated knowledge in general conceptualizations. In this section the efforts of some authors to derive models of central control of micturition from the data available are presented. The goal of this section is to describe the ongoing evolution of the understanding of central control of micturition.
The neuroimaging studies of today rely on the seminal work of many authors who in the twentieth century investigated the suprapontine control of micturition with methods other than neuroimaging. These authors investigated animal models and pathologies in human patients and were able to formulate important hypotheses which still inform the way we understand the control of micturition.
Examples are represented by the work of Barrington , Ueki .
What Barrington had described in the cat as “a part of the brain just ventral to the internal edge of the superior cerebellar peduncle from the level of the V° nerve behind to the level of the anterior end of the hind brain in front” has later been referred to as the M-region by Holstege and colleagues  and as the pontine micturition centre (PMC) by Loewy and colleagues .
Ueki  made important observations about micturition in brain tumour patients. In his study he reported that in brain tumours some kind of dysuria (defined as retardation or retardation combined with protraction) was more frequently observed than incontinence. He also stressed the importance of the role played in micturition by the pons, basically confirming Barrington’s hypothesis that “there are important centres partaking in contracting the bladder (…) somewhere between the pons and the medulla oblongata, and also close to the lower part of the midbrain”.
Until the 1990s there was consensus about the fact that pontine structures were the principal players in micturition control. Later the focus was extended also to suprapontine structures. For example, Blok  summarized the components of neural pathways involved in micturition and continence, underlining that “apparently, centers in the pons coordinate micturition as such, but suprapontine centers are responsible for the beginning of micturition”. He stressed the important practical observation that “patients with suprapontine lesions never show detrusor-sphincter-dyssynergia”.
Later, Fowler and Griffiths presented a “working model of brain activity during bladder filling and emptying” .
Basing on the work of Blok  these authors underlined the importance of “interoception” defined by Craig [14, 15] as “the sense of the physiological condition of the entire body” which not only is limited to visceral sensation but also comprehends the sensation of pain and temperature. The afferent input regarding these stimuli is conducted through small-diameter (Aδ and C) fibres entering the spinal cord through lamina 1, where lamina 1 neurons relate to homeostatic information. These afferents project to subcortical homeostatic centres (i.e. hypothalamus and PAG) converging—after relaying in the thalamus—on the non-dominant anterior insula. This structure can be seen as the “homeostatic afferent cortex” or “the sensory cortex of the autonomic nervous system”  and is activated in a range of tasks involving visceral sensation such as heart rate, respiration, digestive processes and micturition.
Interoceptive sensation is always associated to affective and motivational aspects, which in turn are associated to anterior cingulate cortex (ACC). The ACC can also be seen as “the motor cortex of the autonomic nervous system”, given that it is responsible for emotional, behavioural and motor responses to visceral stimuli. Activity in both structures—insula and ACC—has been shown in functional imaging experiments involving the bladder. These structures together with the hypothalamus and the amygdala form the limbic system which is extensively connected with the orbitofrontal or prefrontal lateral cortex, itself involved in “making the decision whether or not micturition should take place”.
These data allowed Fowler and Griffiths [12, 16] to describe a “brain bladder control matrix”. This matrix involves the following brain structures: brainstem (pons and midbrain), cerebellum, insula and ACC as well as prefrontal cortex (PFC).
Although being a very good attempt to systematize the knowledge about central control of the bladder, this description has two principal limits. On the one hand, it represents a flat map of the structures involved, where connectivity directions are presented as only probable: an attempt to investigate connectivity during visceral interoception has been recently made by Jarrahi and colleagues . On the other hand, it hypothesizes brain activity during bladder filling and emptying, respectively, only generically and in a linear manner.
De Groat and colleagues  tried to further differentiate the central control of bladder function, arranging the structures involved in three different circuits.