Magnetic source imaging combined with image-guided frameless stereotaxy: a new method in surgery around the motor strip

OBJECTIVE: In this study, information about the localization of the central sulcus obtained by magnetic source imaging (MSI) was intraoperatively translated to the brain, using frameless image-guided stereotaxy. In the past, the MSI results could be translated to the surgical space only by indirect methods (e.g., the comparison of the MSI results, displayed in surface renderings, with bony landmarks or blood vessels on the exposed brain surface). METHODS: Somatosensory evoked fields were recorded with a MAGNES II biomagnetometer (Biomagnetic Technologies Inc., San Diego, CA). Using the single equivalent current dipole model, the localization of the somatosensory cortex was superimposed on magnetic resonance imaging with a self-developed contour fit program. The magnetic resonance image set containing the magnetoencephalographic dipole was then transferred to a frameless image-guided stereotactic system. Intraoperatively, the gyrus containing the dipole was identified as the postcentral gyrus, using neuronavigation, and the next anterior sulcus was regarded as the central sulcus. With intraoperative cortical recording of somatosensory evoked potentials, this assumption was verified in each case. RESULTS: In all cases, the preoperatively assumed localization of the central sulcus and motor cortex with MSI agreed with the intraoperative identification of the central sulcus using the phase reversal technique. CONCLUSION: The combined use of MSI and a frameless stereotactic system allows a fast orientation of eloquent brain areas during surgery. This may contribute to a safer and more radical surgery in lesions adjacent to the motor cortex.     

Correlation of functional magnetic source imaging with intraoperative cortical stimulation in neurosurgical patients

This study compared noninvasive preoperative functional imaging by using magnetoencephalography (MEG) with intraoperative direct cortical stimulation in ten patients undergoing neurosurgery. The goal was to assess the accuracy and reliability of MEG-based functional imaging in these patients as a possible replacement or adjunct for direct cortical stimulation with electrocorticography. Objective comparison of intraoperative mapping with preoperative MEG procedures was achieved by intraoperative recording of mapped cortical locations for motor responses using an interactive image-guided surgical device, the ISG viewing wand, with which mapping points could be marked on a previously acquired (MRI) set. In all ten patients, at least one stimulation site elicited a response during both MEG and intraoperative mapping. The central sulcus ipsilateral to the lesion was only directly visible on high-resolution MRIs in 3/10 cases and equivocally in 2/10. Coregistered with MRI to form magnetic source images (MSIs), MEG predictions of the postcentral gyrus were possible in all 10 cases. In all 10 cases, these were in agreement with intraoperative estimation of the precentral gyrus. Functional mapping of somatosensory cortex was achieved noninvasively in surgical patients by using MSI. The accuracy, compared with cortical stimulation, was always sufficient to define motor and somatosensory strips.     

Intra-operative localization of sensorimotor cortex by cortical somatosensory evoked potentials: from analysis of waveforms to dipole source modeling

Intra-operative localization of sensorimotor cortex is of increasing importance as neurosurgical techniques allow safe and accurate removal of lesions around the central sulcus. Although direct cortical recordings of somatosensory evoked potentials (SEPs) are known to be helpful for cortical localization, source localization models can provide more precise estimates than subjective visual analysis. In addition to intra-operative analysis of waveforms and amplitudes of SEPs to median nerve stimulation in 20 neurosurgical patients, we used a spatiotemporal dipole model to determine the location of the equivalent dipoles consistent with the cortical distribution of the SEPs. The early cortical SEPs were modeled by 2 equivalent dipoles located in the postcentral gyrus. The first dipole was primarily tangentially oriented and explained N20 and P20 peaks. The second dipole was primarily radially oriented and explained P25 activity. We found consistent localization of the first dipole in the postcentral gyrus, which was always located within 8 mm of the central sulcus, with an average distance of 3 mm. This finding provides an objective basis for using the SEP phase reversal method for cortical localization. We conclude that dipole source modeling of the cortical SEPs can be considered as an objective way of localizing the cortical hand sensory area.     

Combined utility of functional MRI, cortical mapping, and frameless stereotaxy in the resection of lesions in eloquent areas of brain in children

We studied 16 children with lesions in the eloquent brain to determine if the amalgamation of information from functional magnetic resonance imaging (fMRI), frameless stereotaxy, and direct cortical mapping and recording could facilitate the excision of these lesions while minimizing potential neurological deficits. The mean age of the children was 10 years. Fourteen children presented with seizures. All lesions were located in or near eloquent cerebral cortex. fMRI was successful in all patients in delineating the relationship between the lesion and regions of task-activated cortex. The ISG wand was utilized in all cases for scalp and bone flap placement, and for intraoperative localization of the lesion. Direct cortical stimulation or recording of phase reversals with somatosensory evoked potentials helped delineate the central sulcus and language cortex in patients with lesions near the motor or language cortex. Intraoperative electrocorticography (ECoG) was utilized in all patients who presented with seizures to guide the extent of resection of the epileptiform cortex. Ten children had benign cerebral neoplasms, nine of which were totally resected. The other diagnoses included vascular malformations, Sturge-Weber, tuberous sclerosis, Rasmussen's encephalitis, and primitive neuroectodermal tumor. Only 1 patient with a left Rolandic AVM developed a new neurological deficit postoperatively. Thirteen of fourteen patients who presented with seizure disorders were rendered either seizure free or improved in terms of seizure control postoperatively. Follow-up has ranged from 12 to 18 months, with a mean follow-up of 15 months. We conclude that the techniques of fMRI, frameless stereotaxy, direct cortical stimulation and recording can be utilized in sequence to accurately localize intracerebral lesions in eloquent brain, and to reduce the morbidity of resecting these lesions in children.     

Functional results after resective procedures involving the supplementary motor area

In this article, the authors report their experience with surgically induced supplementary motor area (SMA) deficiency syndrome in a prospective clinical trial of 28 patients who underwent surgery for tumorous (19 patients) or nontumorous (nine patients) lesions. The dominant side was affected in 17 patients and the nondominant side in 11 patients. The primary presenting symptoms included seizure activity (23 patients), hemiparesis (four patients), and aphasia (one patient). Functional topographic mapping, achieved by phase reversal of somatosensory evoked potentials, allowed precise localization of the central sulcus in 25 of the 28 patients. Motor evoked potential (MEP) monitoring, which was performed successfully in 13 of 15 cases during the resective procedure, showed no significant changes in the potentials in any patient. Immediately after surgery, 25 (89%) of the 28 patients displayed additional neurological deficits (aphasia and/or hemiparesis) that depended on the extent of the SMA resection. In 12 patients the SMA was resected completely: nine of these patients demonstrated a complete and three an incomplete deficit. In 16 patients the SMA resection was incomplete: 13 of these patients displayed an incomplete deficit, whereas three had no deficit. Neurological disorders resolved completely within 3 to 42 days (mean 11 days), except for a minimal disturbance of fine motor and/or speech function in complex tasks or at high speed. Electromagnetically elicited MEPs, examined postoperatively in five patients, were initially absent but recovered with improvement of motor function. In conclusion, although the SMA is known to control important functions such as initiation of motor activity or speech, our findings show that unilateral SMA removal can be accomplished without resulting in significant permanent deficits. Functional topographic mapping and monitoring facilitate the exact delineation of the adequate resection plane along the precentral sulcus, and postoperative magnetic resonance imaging allows precise correlation of clinical and anatomical data.     

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We report a case of transient left lateral gaze paresis due to a hemorrhagic lesion restricted in the right precentral gyrus. A 74-year-old female experienced a sudden clumsiness of the left upper extremity. A neurological examination revealed a left central facial paresis, distal dominant muscle weakness in the left upper limb and left lateral gaze paresis. There were no other focal neurological signs. Laboratory data were all normal. Brain CTs and MRIs demonstrated a subcortical hematoma in the right precentral gyrus. The neurological symptoms and signs disappeared over seven days. A recent physiological study suggested that the human frontal eye field (FEF) is located in the posterior part of the middle frontal gyrus (Brodmann's area 8) and the precentral gyrus around the precentral sulcus. More recent studies stressed the role of the precentral sulcus and the precentral gyrus. Our case supports those physiological findings. The hematoma affected both the FEF and its underlying white matter in our case. We assume the lateral gaze paresis is attributable to the disruption of the fibers from the FEF. It is likely that fibers for motor control of the face, upper extremity, and lateral gaze lie adjacently in the subcortical area.     

Cortical activation during fast repetitive finger movements in humans: dipole sources of steady-state movement-related cortical potentials

Fast repetitive finger movements are associated with characteristic EEG patterns described in humans as steady-state movement-related cortical potentials (ssMRCPs). The objective of the present study was to determine the electrical generators of ssMRCPs (movement rate, 2 Hz) by dipole modelling. The generators for the initial ssMRCP phase (peak approximately 60 msec before EMG onset) were located in the central region bilaterally, with largely radial orientation, consistent with activation of the crown of the precentral gyrus. The generator of the next phase (peak approximately 10 msec after EMG onset) was located in the contralateral central region with tangential posterior orientation, consistent with activation of the anterior wall of the central sulcus. The postmovement phase (peak approximately 95 msec after EMG onset) was explained by another source in the contralateral central region with tangential anterior orientation, consistent with activation of the posterior wall of the central sulcus. This pattern probably corresponds to a sequence of activation of the bilateral dorsal premotor cortex, contralateral primary motor, and primary somatosensory cortex that takes place within approximately 200 msec around EMG onset. Steady-state movement-related cortical potentials in combination with dipole modelling provide a novel, noninvasive approach to assessing changes of human cortical premotor, motor, and somatosensory activation in the millisecond range.     

Detection of cortical activities on eye movement using functional magnetic resonance imaging

Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann's areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann's areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement.     

Role of the premotor cortex in recovery from middle cerebral artery infarction

OBJECTIVE: To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. INTERVENTIONS: Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. RESULTS: The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%, P<.001), the motor evoked potentials in the hand and leg muscles contralateral to the infarctions were normal, whereas the somatosensory evoked potentials from the contralateral median nerve were reduced. During fractionated finger movements of the recovered hand, regional cerebral blood flow increases occurred bilaterally in the dorsolateral and medial premotor areas but not in the sensorimotor cortex of either hemisphere. CONCLUSIONS: Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated.     

Precentral glioma location determines the displacement of cortical hand representation

OBJECTIVE: Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS: We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS: Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION: Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.     

Localization of the central sulcus and adjacent sulci in human: a study by MRI

Variations in localization of the central sulcus and the sulci around the central sulcus namely the superior frontal sulcus, precentral sulcus, postcentral sulcus, marginal ramus of cingulate sulcus were studied in vertex sections retrospectively by magnetic resonance imaging (MRI) method in 3580 cases. Out of total number of cases, 1000 who did not show any macroscopic intracranial pathology were carefully selected for research. Additionally, 0-1 age group was excluded from the study because the sulci develop in first year of postnatal life, excluding the possibility of considering these as anatomical variations. Thus, the total number of cases is decreased to 990. 16 variations related to localization of the superior frontal sulcus, precentral sulcus, central sulcus, postcentral sulcus and the marginal ramus of the cingulate sulcus were identified. The asymmetries of the sulci, the most variable sulci and the distribution of the variations according to sex were statistically analysed.     

Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex

To clarify the topographical relationship between peri-Rolandic lesions and the central sulcus, we carried out presurgical functional mapping by using magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) on 5 patients. The sensory cortex was identified by somatosensory evoked magnetic fields using MEG (magnetic source imaging (MSI)). The motor area of the hand region was identified using f-MRI, during a hand squeezing task. In addition, transcranial magnetic stimulation localized the hand motor area on the scalp, which was mapped onto the MRI. In all cases, the sensory cortex was easily identified by MSI and the results of MSI correlated well with the findings obtained by the intraoperative recording of somatosensory evoked potentials. In contrast, the motor cortex could not be localized by f-MRI due to either the activated signal of the large cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions [corrected].     

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation

OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning.     

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Methods to directly and indirectly identify the central sulcus are presented. In the axial plan, direct method is remarkable but obviously requires good visualization of the sulci in the central region. Sulci are readily visible in 90% of the cases on CT scans and in 50% of the cases on MRI. The method can also be applied when tumoral development erases the cerebral sulci by direct lecture of the controlateral rolandic region and right-left transfer. Within the precision limits of the method, it can be considered that the central sulci are symmetrical. The main signs are: the relative morphologies of the superior frontal sulcus and the precentral sulcus, the hook-shaped aspect of the middle part of the central sulcus, the internal end of the central sulcus projection anteriorly to the pars marginalis, the bifid nature of the internal end of the posterior central sulcus contouring the pars marginalis, and the lesser thickness of the posterior central gyrus compared with the precentral gyrus. The indirect method is less precise and is used when the direct method is unsuccessful. The central sulcus is identified on the sagittal images and, using the lateral view of the skull as a reference image, the topographic information is transferred to the axial images.     

Magnetoencephalographic mapping: basic of a new functional risk profile in the selection of patients with cortical brain lesions

OBJECTIVE: Surgical management of cortical lesions adjacent to or within the eloquent cerebral cortex requires a critical risk: benefit analysis of the procedure before intervention. This study introduced a measure of surgical risk, based on preoperative magnetoencephalographic (MEG) sensory and motor mapping, and tested its value in predicting surgical morbidity. METHODS: Forty patients (21 men and 19 women; mean age, 36.5 yr) with cortical lesions (12 arteriovenous malformations and 28 tumors) in the vicinity of the sensorimotor cortex were classified into high-, medium-, or low-risk categories by using the MEG-defined functional risk profile (FRP). This was based on the minimal distance between the lesion margin and the sensory and motor MEG sources, superimposed on a magnetic resonance imaging scan. Case management decisions were based on the MEG mapping-derived FRP in combination with biopsy pathological findings, radiographic findings, and anatomic characteristics of the lesion. A recently developed protocol was used to transform MEG source locations into the stereotactic coordinate system. This procedure provided intraoperative access to MEG data in combination with stereotactic anatomic data displays routinely available on-line during surgery. RESULTS: It was determined that 11 patients diagnosed as having gliomas had high FRPs. The margin of the lesion was less than 4 mm from the nearest MEG dipole or involved the central sulcus directly. A nonoperative approach was used for six patients of this group, based on the MEG mapping-derived FRP. In the group with arteriovenous malformations, 6 of 12 patients with high or medium FRPs underwent nonoperative therapy. The remaining 28 patients, whose lesions showed satisfactory FRPs, underwent uneventful lesion resection, without postoperative neurological deficits. CONCLUSION: Our results suggest that MEG mapping-derived FRPs can serve as powerful tools for use in presurgical planning and during surgery.     

Introduction of magnetoencephalography to stereotactic techniques

Magnetoencephalography (MEG), a noninvasive functional brain mapping technique, was used for preoperative localization of the sensorimotor cortex in patients harboring lesions involving these eloquent regions. Prior to surgery, MEG source locations were transferred onto high-resolution MRI pictures which were then used for preoperative evaluation, risk analysis, and planning. We have developed a process to transform the MEG-derived sensorimotor localization coordinates into the COMPASS stereotactic coordinate system. Thus the MEG-derived functional information is incorporated into the stereotactic database, enabling the simultaneous visualization of functional and anatomical data. This information can be used for the selection of cases and in planning safe approaches for computer-assisted volumetric resections. The integration of MEG and stereotactic neurosurgery also allows a more precise comparison between MEG and intraoperative direct electrocorticographic mapping (ECoG). Seven patients were studied with good correlation between MEG and intraoperative mapping. In 4, the correlation was only based on gross visual comparison between intraoperative identification of the gyrus pattern and MEG photographs. The availability of the MEG coordinates in the stereotactic system, however, allows a more precise correlation between MEG and ECoG. In all 3 patients studied in this manner, the MEG coordinates (pinpointed to a precise cortical representation of a few millimeters) overlapped with ECoG results. In summary, we compared functional MEG data to intraoperative ECoG and conclude that the introduction of MEG into stereotactic neurosurgery can provide precise functional and anatomic information for image-guided surgical planning and resection.     

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OBJECT: The purpose of this study was to evaluate the efficacy of noninvasive preoperative functional imaging data used in an interactive fashion in the operating room. The authors describe a method of registering preoperative functional magnetic resonance (fMR) imaging localization of sensorimotor cortex with a frameless stereotactic surgical navigation device. METHODS: The day before surgery, patients underwent blood oxygen level-dependent fMR imaging while performing a finger-tapping motor paradigm. Immediately afterward an anatomical stereotactic MR image was acquired. Raw fMR imaging data were analyzed offline at a separate workstation, and the resulting functional maps were registered to a high-resolution anatomical scan. The fused functional-anatomical images were then downloaded onto a surgical navigation computer via an ethernet connection. At surgery, the brain was exposed in the standard fashion, and the sensorimotor cortex was identified by direct cortical stimulation, the use of somatosensory evoked potentials, or both. This localization was then compared with that predicted by the registered fMR study. Thirteen procedures were performed in 12 patients. The mean registration error was 2.2 mm. The predicted location of motor and/or sensory cortex matched that found on intraoperative mapping in all 12 patients tested. Maximal tumor resection was accomplished in each case and no new permanent neurological deficits resulted. CONCLUSIONS: Compared with conventional brain mapping techniques, fMR image-guided surgery may allow for smaller brain exposures, localization of the language cortex with the patient under general anesthesia, and the mapping of multiple functional sites. The scanning equipment used in this method may be more readily available than for other functional imaging techniques such as positron emission tomography or magnetoencephalography.     

Motor consequences of motor area ablations in man

Motor disorders reported in the present paper do not result from cortical ablations stricto sensu since some white matter was excised in every patient. However they appear to suggest that, as suggested by Walshe (1935), the central region and premotor area are a functional entity, i.e. they work as a whole. The extensive lesions of the premotor area, leaving untouched the motor region, have the same motor and tonic consequences as lesions limited to the central region. This point which appears specific for man does not imply that the premotor region subserves activities similar to those subserved by the central region. Rather it may suggest a deafferentiation of the central region, the consequences of which would be more important than is generally assumed. Extensive central or premotor lesions determine various tonic disorders: a well known spasticity, with exaggeration of the stretch reflex, associated with an increase in passive swinging of segments of limbs and in extensibility of joints. These two latter phenomena are usually defined as hypotonia. With premotor and precentral lesions the hypotonia disappears and a hemiplegic posture is observed. This hemiplegic posture is a dystonia which apparently does not result directly from the exaggeration of the stretch reflex. Anatomically it appears to result from lesions of both central and premotor regions. This is in agreement with Denny-Brown's (1966) contention that an extrapyramidal region lies rostral to the prerolandic sulcus. As suggested by Evarts (1973) motor regions appear to control automatic as well as voluntary movements. They probably play a role in the trophic function of muscle, since, despite rehabilitation, amyotrophy was present in every case reported in the present paper.     

Morphological investigation of the neuroprotective effects of graded hypothermia after diverse periods of global cerebral ischemia in gerbils

Cerebral dysgenesis is a subject of interest because of its relationship to cerebral development and dysfunction and to epilepsy. The authors present a detailed study of a 16-year-old boy who underwent surgery for a severe seizure disorder. This patient had dysgenesis of the right hemisphere, which was composed of a giant central frontoparietal nodular gray matter heterotopia with overlying large islands of cortical dysplasia around a displaced central fissure. Exceptional insight into the function, biochemistry, electrophysiology, and histological structure of this lesion was obtained from neurological studies that revealed complementary information: magnetic resonance (MR) imaging, [18]fluoro-2-deoxy-D-glucose positron emission tomography (PET), functional PET scanning, proton MR spectroscopic (1H-MRS) imaging, intraoperative cortical mapping and electrocorticography, in vitro electrophysiology, and immunocytochemistry. These studies demonstrated compensatory cortical reorganization and showed that large areas of heterotopia and cortical dysplasia in the central area may retain normal motor and sensory function despite strikingly altered cytoarchitectonic organization and neuronal metabolism. Such lesions necessitate appropriate functional imaging studies prior to surgery and cortical mapping to avoid creating neurological deficits. Integrated studies, such as PET, 1H-MRS imaging, cortical mapping, immunocytochemistry, and electrophysiology may provide information on the function of developmental disorders of cerebral organization.     

Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study

The clinical, electrophysiological and haemodynamic effects of precentral gyrus stimulation (PGS) as a treatment of refractory post-stroke pain were studied in 2 patients. The first patient had a right hemibody pain secondary to a left parietal infarct sparing the thalamus, while the second patient had left lower limb pain developed after a right mesencephalic infarct. In both cases, spontaneous pain was associated with hyperpathia, allodynia and hypoaesthesia in the painful territory involving both lemniscal and extra-lemniscal sensory modalities in patient 1, extra-lemniscal sensory modality only in patient 2. Both patients were treated with electrical PGS by means of a 4-pole electrode, the central sulcus being per-operatively located using the phase-reversal of the N20 wave of somatosensory evoked potentials. No sensory side effect, abnormal movement or epileptic seizure were observed during PGS. The analgesic effects were somatotopically distributed according to the localization of electrode on motor cortex. A satisfactory long-lasting pain control (60-70% on visual analog scale) as well as attenuation of nociceptive reflexes were obtained during PGS in the first patient. Pain relief was less marked and only transient (2 months) in patient 2, in spite of a similar operative procedure. In this patient, in whom PGS eventually evoked painful dysethesiae, no attenuation of nociceptive RIII reflex could be evidenced during PGS. Cerebral blood flow (CBF) was studied using emission tomography (PET) with O-labeled water. The sites of CBF increase during PGS were the same in both patients, namely the thalamus ipsilateral to PGS, cingulate gyrus, orbito-frontal cortex and brainstem. CBF increase in brainstem structures was greater and lasted longer in patient 1 while patient 2 showed a greater CBF increase in orbito-frontal and cingular regions. Our results suggest that PGS-induced analgesia is somatotopically mediated and does not require the integrity of somatosensory cortex and lemniscal system. PGS analgesic efficacy may be mainly related to increased synaptic activity in the thalamus and brainstem while changes in cingulate gyrus and orbito-frontal cortex may be rather related to attentional and/or emotional processes. The inhibitory control on pain would involve thalamic and/or brainstem relays on descending pathways down to the spinal cord segments, leading to a depression of nociceptive reflexes. Painful dysesthesiae during stimulation have to be distinguished from other innocuous sensory side effects, since they may compromise PGS efficacy.