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Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P

Objectives Intention tremor becomes evident only when patients intend to move their body and is characterized by dysmetria. We have developed an on-demand control system that triggers the switching on/off of deep brain stimulation (DBS) instantly for the control of intention tremor. Material and Methods We used surface electrodes for the recording of electromyographic (EMG) activity, and the power of EMG activity was analyzed instantly employing the fast Fourier transform. The on-demand control system switched on DBS when only the power of tremor frequency exceeded the on-trigger threshold, and the system switched off DBS when the total power of EMG activity decreased below the off-trigger threshold. Results The on-demand control system triggered the switching on/off of DBS accurately, and controlled intention tremor completely. Our on-demand control system is small and portable, and suitable for clinical use. Conclusions The on-demand control system for DBS is useful for controlling intention tremor and may decrease the incidence of tolerance to DBS and may be a powerful tool for various applications of neuromodulation therapy.

Objective High-intensity and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex was carried out in poststroke patients with increased spasticity, and the changes in F-wave parameters in comparison with M-wave parameters induced by rTMS were examined. Methods Ten-hertz rTMS pulses were delivered to the primary motor cortex of the lesion side at 110% intensity of the resting motor threshold, and F-waves were obtained from the first dorsal interosseous muscle. F-waves were recorded before (pre-stim) and immediately after the end of rTMS (post-stim) in poststroke patients. Results F-wave persistence and F/M Amp.Ratio increased significantly in patients with lesions in upper motor tract as compared with healthy subjects (Wilcoxon rank sum test, p = 0.00023 and p = 0.0073, respectively). After the rTMS application, both F-wave persistence and F/M Amp.Ratio decreased significantly (paired t-test, p = 0.0095 and p = 0.037, respectively). However, the F-wave amplitude did not show a statistically significant variance in poststroke patients. Conclusions High-frequency suprathreshold rTMS may suppress the F-waves by enhancing the inhibitory effect on spinal excitability through the corticospinal tract, and F-wave persistence and F/M Amp.Ratio can be used to determine the effect of rTMS on patients with increased spasticity.

Introduction. Chronic thalamic stimulation has been confirmed as an effective treatment for tremor. The optimal target has been commonly accepted to be situated within the ventral thalamus, but a standard trajectory of the deep brain stimulation (DBS) electrode has not yet been established. Materials and Methods. A 53-year-old man with an 11-year history of essential tremor was treated by DBS of the thalamus. In this patient, we had a chance to compare the effects of different trajectory angles of the DBS electrode on tremor. Results. Intraoperative stimulation with the DBS electrode temporarily inserted at a high angle to the horizontal plane of the anterior commissure-posterior commissure (AC-PC) line to cover only the nucleus ventralis intermedius (Vim) was not effective. In contrast, stimulation with the DBS electrode permanently implanted at a low angle, covering a wide area extending from the nucleus ventralis oralis (Vo) to the Vim, reduced the tremor. Conclusion. We report on the case of a patient who showed different effects on tremor depending on the trajectory angle of the DBS electrode to the AC-PC line. The insertion trajectory of the DBS electrode may be an important factor for the treatment of tremor.

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa-induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN-DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN-DBS on the hand deformity was a secondary effect on muscular rigidity. STN-DBS is assumed to represent a useful treatment option for striatal hand deformity.

Objective. For targeting the subthalamic nucleus (STN), we attempted to quantify the changes in multiple cell activities by computing the neural noise level and multiple-cell spike density (MSD). Methods. We analyzed the neural noise level and MSD by stepwise recording at every 0.25-mm increment during the final tracking in 90 sides of 45 patients with Parkinson's disease. The MSD was analyzed with cut-off levels ranging from 1.2- to 2.0-fold the neural noise level in the internal capsule or zona incerta in each trajectory. Results. The dorsal boundary of the STN was identified from an increase in the neural noise ratio in all sides. The ventral boundary was identifiable, however, from a decrease in the neural noise ratio in only 70 sides (78%). In contrast, both the dorsal and ventral boundaries were clearly identified from an increase and a decrease in the MSD, respectively, in all of the 90 sides. Conclusion. MSD analysis by semimicroelectrode recording represents a useful, practical, and apparently reliable means for identifying the boundaries of the STN.

Background Cortical stimulation via a subdural grid electrode (SGE) is one of the most reliable methods for identifying eloquent areas before surgery. However, the physiological conditions of the cortex during stimulation cannot be monitored electrophysiologically because of electrical artifacts. In the present case, we tested whether or not multichannel near-infrared spectroscopy (NIRS) topography, a noninvasive optical imaging technique, is applicable for monitoring the physiological conditions of the stimulated cortex. Case description The patient (a 27-year-old right-handed man) suffered from glioma in the left frontal lobe. For preoperative cortical mapping, SGEs were implanted over the left motor cortex before tumor resection. Employing NIRS topography, we undertook 2 dimensional imaging of the changes in oxyhemoglobin (Oxy-Hb) and deoxyhemoglobin (Deoxy-Hb) concentration during electrical stimulation. Five-hertz stimulation with 5 mA at the left-hand area produced a localized increase in Oxy-Hb and a decrease in Deoxy-Hb, associated with slight twitching of the right hand. In contrast, 50-Hz stimulation produced significant increases in both Oxy-Hb and Deoxy-Hb at the stimulation site, and the area with such cerebral blood oxygenation (CBO) changes propagated beyond the hand area associated with prominent muscle contractions of the right upper extremity, suggesting that 50-Hz stimulation caused epileptic discharge. Conclusion Near-infrared spectroscopy topography may represent a useful tool for imaging the degree and extent of the physiological effects of electrical stimulation on the cortex, and permits safe and accurate cortical mapping.

Clinical course and characteristics of the motor deficits were investigated in patients who underwent surgical resection of the frontal lobe for tumorous lesions. The extent of resection was classified into four groups. In Group A, resection was limited within the area above the superior frontal sulcus and posterior to a line vertical to the AC-PC line at the AC (VCA line). Resection was extended anterior to the VCA line in Group B or below the superior frontal sulcus in Group C. In Group D, resection was extended to both of these two boundaries. In results, permanent and severe motor deficit is rarely induced when resection of the frontal lobe is limited to only the SMA proper (corresponding roughly to Group A), the SMA proper and pre-SMA (corresponding roughly to Group B), or the SMA proper and premotor cortex (corresponding roughly to Group C), insofar as the primary motor cortex is preserved. Disturbance in fine movements of the upper extremity is frequently induced for the long term when wide areas of the SMA proper, pre-SMA as well as premotor cortex are resected all together (corresponding roughly to Group D).

It has become increasingly popular to use functional magnetic resonance imaging (fMRI) as a tool for preoperative functional brain mapping. We, however, have sometimes experienced the eloquent area (localized by fMRI), which did not match-up with the results from the intraoperative electrical cortical mapping. In this study, to clarify a reliability of fMRI, such cases were reported in detail and mechanisms would cause that phenomenon were discussed. Seventeen patients with brain tumor located in the region of motor and/or language cortex were investigated, and high dissociation between fMRI and electrical cortical mapping was noted in four cases. Of the four cases, two cases were reported their clinical course and studied the deoxyhemoglobin (Deoxy-Hb) consumption using near infrared spectroscopy (NIRS) during task performance. As a result, decreasing of Deoxy-Hb during the task was not shown. Blood oxygen level-dependent (BOLD) signals, which were observed in normal brain, would not be expected in the case where a brain tumor is close to the eloquent area. It suggests that fMRI cannot always localize the eloquent area in pathological brain. Therefore, care must be taken to adopt the information from fMRI, when operative strategy is going to be made.

Dystonia is a movement disorder characterized by sustained muscle contractions leading to twisting movements and abnormal postures. There is no certain medical treatment such as ablative surgical treatment, which has often been disappointing. Recently, deep brain stimulation has become well established as a safe and effective therapy in the treatment of movement disorders. In this study, five cases of dystonia underwent the deep brain stimulation (DBS) targeted in globus pallidus internus (GPi); these cases shall be reported on. Among them, two cases were generalized dystonia and three cases of them were cervical dystonia. The electrode for chronic stimulation was inserted by a stereotactic surgical procedure. During the surgery, unitary potentials were recorded in order to decide the appropriate electrode location. The results were evaluated with Fahn–Marsden dystonia movement scales for generalized dystonia and a modified Toronto Western Spasmodic Torticollis Rating Scale for cervical dystonia. As a result, no complication caused by surgery and/or electrical stimulation was noted in these cases. The averages of the scale change, 6 months after the surgery, improved both types of dystonia. The chronic GPi stimulation therapy would be expected as an effective treatment for dystonia.

The results of a double blinded evaluation of the effects of globus pallidus (GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with advanced Parkinson's disease are summarized. The patients were evaluated at 6–8 months after surgery. In order to determine the benefits afforded by the stimulation to the actual daily activities, the patients were maintained on-medication with optimal doses and schedules. The stimulation was turned off overnight for at least 12 h. It was turned on in the morning (or maintained turned off), and the best and worst scores during daytime activity were recorded, as on-period and off-period scores, respectively. A reduction in total motor score on the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN stimulation at both the off-period (−57 and −29%, respectively) and the on-period (−36 and −25%, respectively). The difference in effects between GPi and STN stimulation appeared to be due largely to an unintended difference in the patients’ preoperative symptoms. The benefits provided by stimulation to the actual daily activities appears to be limited in patients who have become unresponsive to a large dose of levodopa. Two advantages of GPi and STN stimulation were identified. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia. Clinically important improvement was observed in severe gait freezing in 2 patients following unilateral anterodorsal GPi stimulation on the right side alone.

This is the first thesis describing a new technique for awake craniotomy using a laryngeal mask. Awake craniotomy with propofol infusion has become increasingly popular for the optimal excision of brain tumours located in eloquent areas. During awake craniotomy, tracheal intubation is not performed and propofol infusion is limited to within doses which render the patient just sedated. This asleep-awake procedure is occasionally associated with difficulty in controlling brain volume, especially in patients with a significant mass effect of their brain tumours, since sufficient sedation with propofol tends to cause hypercapnea. We report an intraoperative wake-up procedure employing a laryngeal mask, which enables general anaesthesia to be performed at a sufficient dose of propofol and with control of the brain volume under mechanically assisted ventilation. Before the beginning of cortical mapping, propofol infusion is completely terminated, so allowing the patient to wake up within 5-15 min. Following completion of the tumour excision, general anaesthesia is re-induced at a sufficient dose of propofol. The laryngeal mask can be temporarily removed and repositioned with ease, if necessary. In our experience, this technique is applicable for the optimal excision of brain tumours, especially in patients who are very obese or those who have very large lesions.

Corticospinal MEP (D-wave), cortico-muscular MEP in response to direct motor cortex stimulation, and subcortico-spinal MEP (subcortical D-wave) in response to subcortical pyramidal tract stimulation were monitored in patients with brain tumors around the motor cortex who showed no obvious motor disturbance before the operation. We could not establish the definite warning criteria of the cortico-muscular MEP, because disappeared cortico-muscular MEP reappeared during the operation. We concluded that cortico-muscular MEP is a safety range monitoring, and cortico-muscular MEP can guarantee the preserved motor function if no obvious change occurred during the tumor resection. On the other hand, monitoring of the D-wave enabled the function of the corticospinal tract to be evaluated selectively. A decrease of less than 30% may indicate postoperative preservation of motor function, including transient motor disturbance with subsequent complete recovery. Monitoring of the subcortical D-wave is useful to know the distance from the pyramidal tract. Intraoperative monitoring of D-wave and subcortical D-wave allows maximum resection of brain tumors located around the motor cortex.

We analyzed the features of neuronal activities, (a) firing rate, (b) firing pattern, and (c) response to passive joint movement, recorded from the globus pallidus internus (GPi) of patients with dystonia (DT) and Parkinson’s disease (PD). The spontaneous firing rate of GPi neurons in DT tended to be lower than that in PD. The reduced GPi activity resulted in disinhibition of thalamocortical pathways, which could cause DT as a form of hyperkinesia. However, identifying this reduced GPi activity is inconsistent with alleviation of DT in patients with pallidotomy. The pathology of DT, thus, cannot be explained solely by the reduced GPi activity. Quantitative examination of pauses and bursts from interspike intervals showed that pauses and bursts were significantly higher in DT than in PD. These abnormal firing patterns are conjectured to disrupt signaling along cerebello-thalamocortical pathways, impairing motor control and resulting in DT. Thus, abnormal firing patterns may represent temporal dysfunction. Changes in the GPi included enlargement of the receptive fields and an increased number of neurons exhibiting inhibitory reactions. DT symptoms may arise because of dysfunction of the mechanism inhibiting unrequired movements. The abnormal changes in the neurons in DT may underlie spatiotemporal dysfunction.

Spinal cord stimulation (SCS) is used to treat for several types of intractable pain syndromes, but it is not commonly used for treating post-stroke pain. Therefore, in this study, we analyzed the effects of SCS in patients with post-stroke pain. Neurological imaging and pharmacological analysis using thiopental, ketamine and morphine tests were conducted for 30 patients with post-stroke pain. For all patients, percutaneous electrodes were inserted under local anesthesia, and trial stimulation was performed for 5–7 days. If the patient experienced pain relief during the trial stimulation, a pulse generator was implanted. Of the 30 patients, 26 (87%) experienced satisfactory pain relief and underwent implantation. Ten patients received dual-octad lead SCS. The stimulation induced adequate paresthesia in all 10 patients. Nine (90%) of the 10 patients experienced satisfactory pain relief and opted for pulse generator implantation in order to proceed with the treatment. Upper cervical SCS was performed for patients with pain in not only the upper and lower extremities but also the face. Upper cervical SCS provided good paresthesia coverage and was effective for such patients. We think that patients with post-stroke pain may respond favorably to dual-octad lead SCS, and advancements in devices for SCS would further improve treatment outcomes for such patients.

through: (1) Somatosensory evoked potential phase reversal technique; (2) DCS with a short train of 5 7 monopolar stimuli (0.5ms duration, ISI 4.1, intensity up to 20mA) at 1 2Hz. To monitor motor pathways during tumor removal, MEPs are recorded from controlateral limb muscles after either DCS and/or transcranial electrical stimulation. When approaching tumor borders, MEP monitoring is combined with periodical direct subcortical stimulation (DSS) to localize the corticospinal tract (CT) and guide resection.A more than 75% drop in transcranial MEP amplitude at the end of surgery, and a DSS thresholds lower than 3 4mA are associated to post-operative neurological worsening. However these two neurophysiological warning signs are not significantly related and do not necessarily identify the same patients, suggesting that continuous MEP monitoring and periodical subcortical mapping should be combined to minimize risks. Recently, thanks to the introduction of diffusion tensor imaging and neuronavigation, there has been an increasing interest for the correlation of fiber tractography with subcortical stimulation. This work is providing some degree of reliability in the assessment of subcortical current spreading. Preliminary data suggest that 1mA = 1mm may be an acceptable practical parameter to judge on the distance from the CT, when using subcortical mapping.

The modulatory effects of diencephalic stimulation on the activities of raphe-spinal neurons were studied extracellularly in cats. Among 240 raphe neurons recorded, 57 neurons were activated antidromically by stimulation of the cervical dorsolateral funiculus. These raphe-spinal neurons were found in the caudal raphe nuclei, i.e., the raphe magnus (43 neurons), raphe obscurus (11), raphe pallidus (2), and raphe pontis (1). All of them responded to innocuous and/or noxious peripheral mechanical stimuli with a broad receptive field. The activities of the majority of these neurons were facilitated by trains of pulse stimulation of the rostral periaqueductal gray and the thalamic relay nucleus but not of the thalamic center median nucleus. The facilitation of firing persisted for more than 3 min after the cessation of train pulse stimulation when the stimulation was applied at 20 Hz for 5 to 30 s. This facilitation was not affected by decortication of the sensorimotor area bilaterally. The facilitatory response to periaqueductal gray stimulation was markedly suppressed by systemic administration of naloxone. On the other hand, that of the thalamic relay nucleus stimulation was found to be unaffected. Based on these findings, the mechanisms of pain relief by stimulation of the rostral periaqueductal gray and thalamic relay nucleus reported in human intractable pain appear to relate, at least partly, to the activation of raphe-spinal neurons. However, the paths to raphe-spinal neurons of stimuli from the periaqueductal gray and the thalamic relay nucleus are thought to be independent from each other based on the different effects of naloxone.

To determine preoperatively the level of lesions in acute cervical cord injury, the killed end potential of the spinal cord was recorded with a pair of electrodes placed in the spinal epidural space, one initially being placed rostrally to the lesions for obtaining recordings and the other placed caudally to the lesions for stimulation. The level associated with the largest killed end potential was clearly determined without much difficulty, with sequential recordings on stepwise withdrawal of the recording electrode, in four of five cases investigated. In two cases subjected to surgery, the recording electrode left in place at the level associated with the largest killed end potential was found to be located at, or a few millimeters below, the center of the lesions. This demonstrates the preoperative localizing value of the killed end potential for determining the level of lesions responsible for myelopathy.