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is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. The present article reviews relevant literature on procedures or devices applied either in contact with the cerebral cortex or cranial nerves or in deep sites inside the brain in order to treat various refractory neurological conditions such as: a) chronic pain (facial, somatic, deafferentation, phantom limb), b) movement disorders (Parkinson’s disease, dystonia, Tourette syndrome), c) epilepsy, d) psychiatric disease, e) hearing deficits, and f) visual loss. These data indicate that in operative neuromodulation, a new field emerges that is based on neural networks research and on advances in digitised stereometric brain imaging which allow precise localisation of cerebral neural networks and their relay stations; this field can be described as because it aims to act extrinsically or intrinsically on neural networks and to alter therapeutically the neural signal transmission with the use of implantable electrical or electronic devices. The authors also review neurotechnology literature relevant to neuroengineering, nanotechnologies, brain computer interfaces, hybrid cultured probes, neuromimetics, neuroinformatics, neurocomputation, and computational neuromodulation; the latter field is dedicated to the study of the biophysical and mathematical characteristics of electrochemical neuromodulation. The article also brings forward particularly interesting lines of research such as the carbon nanofibers electrode arrays for simultaneous electrochemical recording and stimulation, closed-loop systems for responsive neuromodulation, and the intracortical electrodes for restoring hearing or vision. The present review of cerebral neuromodulatory procedures highlights the transition from the conventional neurosurgery of resectiveor ablative techniques to a highly selective “surgery of networks”. The dynamics of the convergence of the above biomedical and technological fields with biological restorative approaches have important implications for patients with severe neurological disorders.

Two approaches are utilized when targeting the brain to treat pain. The first, a non-destructive approach, uses either electrical stimulation of brain targets thought to modulate the process of pain perception, or pharmacological agents are introduced into ventricular spaces to target pain modulating receptors. Electrical stimulation targets include; the thalamic nuclei, the periventricular and periaqueductal grey (PVG and PAG) matter or the motor cortex. Currently, the pharmacological agent of choice for intracerebroventricular injection is morphine. In general, electrical stimulation is used for nonmalignant type pain, and pharmacological modulation for malignant type pain. The second, a destructive approach, is usually employed with the goal of interrupting the signals that lead to pain perception at various levels. Neuroablation is usually performed on cellular complexes such as “nuclei, or gyri” or on tracts with the aim of disrupting the sensory and limbic pathways involved in the emotional processes associated with pain. Specific cerebral neuroablation targets include; the thalamic medial group of nuclei, the cingulated gyrus, and the trigeminal nucleus and tract. There are fewer reports in the literature detailing the brain, when compared to the spine, as a target to treat pain, and further research is required.

Central pain results from a central nervous system injury and represents a challenge for the pain therapist. Human studies have shown that motor cortex stimulation (MCS), i.e. the placement of a stimulating plate on the dura overlying the motor cortex can relieve brain central pain. Studies suggest that MCS directly affects activity in the first and second order somatosensory areas, thalamic nuclei and also inhibits spinal primary afferents and spinothalamic tract neurons. The following factors have been found to predict analgesia by MCS: intact or almost intact corticospinal motor function, mild or negligible sensory loss, absence of thermal sensory threshold alteration within the painful area, positive response to the barbiturate and/or ketamine test, positive response to the propofol test, positive response to transcranial magnetic stimulation (TMS). The targeting of the cortical area is made by anatomical localization by computed tomography (CT), magnetic resonance imaging (MRI), neuronavigation, intraoperative neurophysiological recordings, functional MRI (fMRI), and intraoperative clinical assessment. We perform the procedure under local anaesthesia.We describe in detail our surgical technique and stimulation protocol. Furthermore, we review the most important studies with respect to their results, the observed side effects and complications. The future prospects and likely developments of MCS for central pain are also discussed.

Since the initial publication of Tsubokawa in 1991, epidural motor cortex stimulation (MCS) is increasingly reported as an effective surgical option for the treatment of refractory neuropathic pain although its mechanism of action remains poorly understood. The authors review the extensive literature published over the last 15 years on central and neuropathic pain. Optimal patient selection remains difficult and the value of pharmacological tests or transcranial magnetic stimulation in predicting the efficacy of MCS has not been established. Pre-operative functional magnetic resonance imaging (fMRI), 3-dimensional volume MRI, neuronavigation and intra-operative neurophysiological monitoring have contributed to improvements in the technique for identifying the precise location of the targeted motor cortical area and the correct placement of the electrode array. MCS should be considered as the treatment of choice in post-stroke pain, thalamic pain or facial anesthesia dolorosa. In brachial plexus avulsion pain, it is preferable to propose initially dorsal root entry zone (DREZ)-tomy; MCS may be offered after DREZotomy has failed to control the pain. In our experience, the results of MCS on phantom limb pain are promising. In general, the efficacy of MCS depends on: a) the accurate placement of the stimulation electrode over the appropriate area of the motor cortex, and b) on sophisticated programming of the stimulation parameters. A better understanding of the MCS mechanism of action will probably make it possible to adjust better the stimulation parameters. The conclusions of multicentered randomised studies, now in progress, will be very useful and are likely to promote further research and clinical applications in this field.

Motor cortex stimulation (MCS) was proposed by Tsubokawa in 1991 for the treatment of post-stroke thalamic pain. Since that time, the indications have been increased and included trigeminal neuropathic pain and later other types of central and peripheral deafferentation pain. The results reported in the literature are quite good; the mean long-term success rate is 80% in facial pain and 53% in non-facial pain. Our own results are less impressive: 4 of 14 patients (28%) experienced a greater than 40% pain relief, but in 2 of them the effect faded with time. Only few minor complications have been reported. The accurate placement of the epidural electrode over the motor cortex that somatotopically corresponds to the painful area is believed to be essential for pain relief. Predictive factors included the response to pharmacological tests, the relative sparing from the disease process of the cortico-spinal tract and the sensory system, and the analgesic response achieved during the test period of MCS. A possible predictive factor might be a test of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. MCS may act by rebalancing the control of non-nociceptive sensory inputs over nociceptive afferents at cortical, thalamic, brainstem and spinal level. In addition, it may interfere with the emotional component of nociceptive perception. Biochemical processes involving endorphins and GABA may also be implicated in the mechanism of MCS. It is time for a large multicenter prospective randomized double blind study evaluating not only the effect of MCS on pain (based on the available guidelines for assessment of neuropathic pain), but also the optimal electrode placement and stimulation parameters, and the possible relationship with the response to rTMS. New electrode design and a new generation of stimulators may help in improving the results.

The stimulation of the primary motor cortex (M1) has proved to be an effective treatment for intractable deafferentation pain. This treatment started in 1990, and twenty-eight studies involving 271 patients have been reported so far. The patients who have been operated on were suffering from post-stroke pain (59%), trigeminal neuropathic pain, brachial plexus injury, spinal cord injury, peripheral nerve injury and phantom-limb pain. The method of stimulation was: a) epidural, b) subdural, and c) within the central sulcus. Overall, considering the difficulty in treating central neuropathic pain, trigeminal neuropathic pain and certain types of refractory peripheral pain, the electrical stimulation of M1 is a very promising technique; nearly 60% of the treated patients improved with a higher than 50% pain relief after several months of follow-up and sometimes of a few years in most reports. The mechanism of pain relief by the electrical stimulation of M1 has been under investigation. Recently, repetitive transcranial magnetic stimulation (rTMS) of M1 has been reported to be effective on deafferentation pain. In the future, rTMS may take over from electrical stimulation as a treatment for deafferentation pain.

The conditions of motor cortex stimulation (MCS) applied with epidural electrodes, in particular monopolar (cathodal or anodal) and bipolar stimulation, are discussed. The results of theoretical studies, animal experiments and clinical studies lead to similar conclusions. Basically, cortical nerve fibres pointing at the epidural electrode and those normal to this direction are activated by anodal and cathodal stimulation, respectively. Because MCS for the relief of chronic pain is generally applied bipolarly with electrodes at a distance of at least 10mm, stimulation may actually be bifocal. The polarity and magnitude of a stimulus needed to recruit cortical nerve fibres varies with the calibre and shape of the fibres, their distance from the electrode and their position in the folded cortex (gyri and sulci). A detailed analysis of intra-operative stimulation data suggests that in bipolar MCS the anode of the bipole giving the largest motor response in the pain region is generally the best electrode for pain management as well, when connected as a cathode. These electrode positions are most likely confined to area 4.

Functional neuroimaging has demonstrated that a relationship exists between the intensity of deafferentation pain and the degree of deafferentation- related reorganization of the primary somatosensory cortex. It has also revealed that this cortical reorganization can be reversed after the attenuation of pain. Deafferentation pain is also associated with hyperactivity of the somatosensory thalamus and cortex. Therefore, in order to suppress pain, it seems logical to attempt to modify this deafferentation- related somatosensory cortex hyperactivity and reorganization. This can be achieved using neuronavigation-guided transcranial magnetic stimulation (TMS), a technique that is capable of modulating cortical activity. If TMS is capable of suppressing deafferentation pain, this benefit should be also obtained by the implantation of epidural stimulating electrodes over the area of electrophysiological signal abnormality in the primary somatosensory cortex. The first studies demonstrated a statistically significant pain suppression in all patients and a clinically significant pain suppression in 80% of them. This clinical experience suggests that somatosensory cortex stimulation may become a neurophysiology- based new approach for treating deafferentation pain in selected patients. In this chapter, we review the relevant recent reports and describe our studies in this field.

According to recent clinical data, motor cortex stimulation (MCS) is an alternative treatment for central pain syndromes. We present our minimal invasive technique of image guidance for the placement of motor cortex stimulating electrode and assess the clinical usefulness of both neuronavigation and vacuum headrest. Neuronavigation was used for identification of precentral gyrus and accurate planning of the single burr-hole. The exact location was reconfirmed by intraoperative phase reversal of somatosensory evoked potential (SSEP) and clinical response after electrical stimulation test. Implementation of navigation technique facilitated localization of the precentral gyrus with a high degree of accuracy. Determination of stimulating electrode placement was possible in every case. Postoperative clinical and neuroradiological evaluations were performed in each patient. All patients experienced postoperative relief from pain. Our preliminary series may confirm image guidance as a useful tool for surgery of MCS. Additionally, minimal and safe exposure can be performed using a single burr-hole and vacuum head rest.

The analgesic efficacy of cortical stimulation on refractory neuropathic pain has been established. Although it offers pain relief to 45–75% of the patients, this technique remains under evaluation and the definitive protocol for its application has not been established yet. The mechanisms underlying the analgesic efficacy of cortical stimulation are still largely unknown. Successive technical adaptations have been proposed and tried in order to reduce the number of non-responding patients. In this chapter, we summarize the limited amount of crucial information that has been acquired so far on pain processing in the central nervous system, on the functional pathophysiology of neuropathic pain and on the mechanisms underlying the efficacy of cortical stimulation. We also discuss key issues that could help to increase the success rate and enhance the future prospects of the technique.