Haruhiko Kishima

Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex

Abstract The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation‐guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10‐s 5‐Hz TMS pulses, with 50‐s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF‐MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p < 0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p < 0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.

Functional Recovery in a Primate Model of Parkinson's Disease following Motor Cortex Stimulation

A concept in Parkinsons disease postulates that motor cortex may pattern abnormal rhythmic activities in the basal ganglia, underlying the genesis of observed motor symptoms. We conducted a preclinical study of electrical interference in the primary motor cortex using a chronic MPTP primate model in which dopamine depletion was progressive and regularly documented using 18F-DOPA positron tomography. High-frequency motor cortex stimulation significantly reduced akinesia and bradykinesia. This behavioral benefit was associated with an increased metabolic activity in the supplementary motor area as assessed with 18-F-deoxyglucose PET, a normalization of mean firing rate in the internal globus pallidus (GPi) and the subthalamic nucleus (STN), and a reduction of synchronized oscillatory neuronal activities in these two structures. Motor cortex stimulation is a simple and safe procedure to modulate subthalamo-pallido-cortical loop and alleviate parkinsonian symptoms without requiring deep brain stereotactic surgery.

Testing of semichronically implanted retinal prosthesis by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa.

PURPOSE To examine the safety and effectiveness of a retinal prosthesis that is implanted semichronically in two patients with advanced retinitis pigmentosa (RP). METHODS Two eyes of two patients with advanced RP had a retinal prosthesis implanted in a sclera pocket of one eye. The visual acuity of both eyes before the implantation was bare light perception. Phosphenes were elicited by suprachoroidal-transretinal stimulation (STS). The internal devices of the STS were implanted under the skin on the temporal side of the head, and the 49 electrode-array was implanted in the scleral pocket of one eye. Biphasic electrical pulses (duration, 0.5 ms; frequency, 20 Hz) were delivered through nine active electrodes. The threshold current was determined by currents ≤1 mA. Behavioral tasks were used to determine the functioning of the prosthesis. RESULTS The surgery was completed without a retinal detachment and retinal/vitreous hemorrhage. The implanted STS system remained functional for the 4-week test period. Phosphenes were elicited by currents delivered through six electrodes in Patient 1 and through four electrodes in Patient 2. The success of discriminating two bars was better than the chance level in both patients. In Patient 2, the success of a grasping task was better than the chance level, and the success rate of identifying a white bar on a touch panel increased with repeated testing. CONCLUSIONS Semichronic implantation of a microelectrode-STS system showed that it was safe and remained functional for at least 4 weeks in two patients with advanced RP. (www.umin.ac.jp/ctr number, R000002690.).

Electrocorticographic Control of a Prosthetic Arm in Paralyzed Patients

Paralyzed patients may benefit from restoration of movement afforded by prosthetics controlled by electrocorticography (ECoG). Although ECoG shows promising results in human volunteers, it is unclear whether ECoG signals recorded from chronically paralyzed patients provide sufficient motor information, and if they do, whether they can be applied to control a prosthetic.

Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors

A noninvasive technique for assessing tumor tissue characteristics is required to assist preoperative surgical planning for malignant brain tumors. Preoperative information on tumor cell density within a tumor would help better define the target for tumor biopsy, resulting in more accurate diagnosis and grading of malignant brain tumors. One possible source of this information is diffusion tensor imaging (DTI), although to date studies have focused on its ability to delineate white matter fiber tracks by fiber-tracking and to detect tumor infiltration around the tumor and normal white matter interface. However, the use of DTI for providing information on cell density has also been examined, although with the controversial results. In addition the exact relationships between cell density and the two key values that DTI provides, namely fractional anisotropy (FA) and mean diffusivity (MD), still need to be investigated. In the present study we performed a retrospective investigation of tumor cell density and FA and MD values in biopsy cases. We found that FA has a good positive correlation (R=0.75) and MD has a good negative correlation (R=0.70) with tumor cell density within the tumor core. Similar correlation was observed between the Ki-67 labeling index and FA (R=0.71) and MD (R=0.62). Thus, measurement of both FA and MD within the tumor core has a potential to provide detailed information on tumor cell density within the tumor. Although data obtained from DTI should be interpreted carefully and comprehensively with other imaging modalities such as positron emission tomography, DTI seems to be informative for planning the best biopsy target containing the highest cell density.

Real-time control of a prosthetic hand using human electrocorticography signals

OBJECT A brain-machine interface (BMI) offers patients with severe motor disabilities greater independence by controlling external devices such as prosthetic arms. Among the available signal sources for the BMI, electrocorticography (ECoG) provides a clinically feasible signal with long-term stability and low clinical risk. Although ECoG signals have been used to infer arm movements, no study has examined its use to control a prosthetic arm in real time. The authors present an integrated BMI system for the control of a prosthetic hand using ECoG signals in a patient who had suffered a stroke. This system used the power modulations of the ECoG signal that are characteristic during movements of the patients hand and enabled control of the prosthetic hand with movements that mimicked the patients hand movements. METHODS A poststroke patient with subdural electrodes placed over his sensorimotor cortex performed 3 types of simple hand movements following a sound cue (calibration period). Time-frequency analysis was performed with the ECoG signals to select 3 frequency bands (1-8, 25-40, and 80-150 Hz) that revealed characteristic power modulation during the movements. Using these selected features, 2 classifiers (decoders) were trained to predict the movement state--that is, whether the patient was moving his hand or not--and the movement type based on a linear support vector machine. The decoding accuracy was compared among the 3 frequency bands to identify the most informative features. With the trained decoders, novel ECoG signals were decoded online while the patient performed the same task without cues (free-run period). According to the results of the real-time decoding, the prosthetic hand mimicked the patients hand movements. RESULTS Offline cross-validation analysis of the ECoG data measured during the calibration period revealed that the state and movement type of the patients hand were predicted with an accuracy of 79.6% (chance 50%) and 68.3% (chance 33.3%), respectively. Using the trained decoders, the onset of the hand movement was detected within 0.37 ± 0.29 seconds of the actual movement. At the detected onset timing, the type of movement was inferred with an accuracy of 69.2%. In the free-run period, the patients hand movements were faithfully mimicked by the prosthetic hand in real time. CONCLUSIONS The present integrated BMI system successfully decoded the hand movements of a poststroke patient and controlled a prosthetic hand in real time. This success paves the way for the restoration of the patients motor function using a prosthetic arm controlled by a BMI using ECoG signals.

Determination of language dominance with synthetic aperture magnetometry: comparison with the Wada test.

Cerebral dominance for language function was investigated with synthetic aperture magnetometry (SAM). The results were compared with those of the Wada test. SAM is a spatial filtering technique that enables demonstration of the spatiotemporal distribution of oscillatory changes (synchronization and desynchronization) in magnetoencephalography (MEG) signals elicited by specific brain activation. MEG was conducted during a silent reading task in 20 consecutive preoperative neurosurgical patients who also underwent a Wada test. The spatial distribution of oscillatory changes related to silent reading was shown tomographically with SAM as statistical images. Language dominance was estimated by the laterality index, which scales the lateralization of the beta (13-25 Hz) and low gamma (25-50 Hz) band desynchronizations in the inferior frontal gyrus (IFG) or middle frontal gyrus (MFG). Oscillatory changes were distributed multifocally and bilaterally in the occipital cortex, IFG or MFG, and temporo-parieto-occipital border regions. In 19 patients (95%), language lateralization estimated by the laterality index was congruent with the result of the Wada test. In left-handed patients, SAM analysis clearly differentiated language dominance (left, right, or bilateral), and the findings were confirmed by the Wada test. Lateralization of beta or low gamma band desynchronizations in the IFG or MFG is a good indicator of the side of language dominance. Reliability of MEG imaging with SAM is sufficient to evaluate language dominance preoperatively in neurosurgical patients.

Reduction of intractable deafferentation pain due to spinal cord or peripheral lesion by high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex

OBJECT The authors previously reported that navigation-guided repetitive transcranial magnetic stimulation (rTMS) of the precentral gyrus relieves deafferentation pain. Stimulation parameters were 10 trains of 10-second 5-Hz TMS pulses at 50-second intervals. In the present study, they used various stimulation frequencies and compared efficacies between two types of lesions. METHODS Patients were divided into two groups: those with a cerebral lesion and those with a noncerebral lesion. The rTMS was applied to all the patients at frequencies of 1, 5, and 10 Hz and as a sham procedure in random order. The effect of rTMS on pain was rated by patients using a visual analog scale. RESULTS The rTMS at frequencies of 5 and 10 Hz, compared with sham stimulation, significantly reduced pain, and the pain reduction continued for 180 minutes. A stimulation frequency of 10 Hz may be more effective than 5 Hz, and at 1 Hz was ineffective. The effect of rTMS at frequencies of 5 and 10 Hz was greater in patients with a noncerebral lesion than those with a cerebral lesion. CONCLUSIONS High-frequency (5- or 10-Hz) rTMS of the precentral gyrus can reduce intractable deafferentation pain, but low-frequency stimulation (at 1 Hz) cannot. Patients with a noncerebral lesion are more suitable candidates for high-frequency rTMS of the precentral gyrus.

Encapsulated GDNF-producing C2C12 cells for Parkinson's disease: a pre-clinical study in chronic MPTP-treated baboons

Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor with restorative effects in a variety of rodent and primate models of Parkinsons disease (PD), could be of therapeutic value to PD. In this study, we show that intraventricular chronic infusion of low doses of GDNF using encapsulated genetically engineered C2C12 cells can exert: (1) transient recovery of motor deficits (hypokinesia); (2) significant protection of intrinsic striatal dopaminergic function in the immediate vicinity of the site of implantation of the capsule in the caudate nucleus, and (3) significant-long-lasting-neurotrophic properties at the nigral level with an increase volume of the cell bodies. These observations confirm the potent neurorestorative potential of GDNF in PD and the safety/efficacy of the encapsulation technology as a means to deliver in situ this neurotrophic cytokine even using an intraventricular approach.

Diffusion tensor fiber tracking in patients with central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic stimulation.

Abstract Central post‐stroke pain (CPSP) is one of the most common types of intractable pain. We reported that repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex relieves pain for patients who were refractory to medical treatment. But the mechanism is unclear. In the present study, we investigated relations between the characteristics of CPSP and the results of fiber tracking, which is the only noninvasive method of evaluating the anatomical connectivity of white matter pathways. Fiber tracking of the corticospinal tract (CST) and thalamocortical tract (TCT) was investigated in 17 patients with CPSP. The stroke lesion was located in a supratentorial region in all cases (corona radiata, one case; thalamus, seven cases; putamen, nine cases). Relations between the delineation ratio (defined as the ratio of the cross section of the affected side to that of the unaffected side) of the CST and of the TCT, manual muscle test score, pain score, region of pain, and efficacy of rTMS were evaluated. Fiber tracking was successful in 13 patients with the stroke lesion involving the TCT. The rTMS‐effective group had higher delineation ratio of the CST (p = 0.02) and the TCT (p = 0.005) than the rTMS‐ineffective group. Previous studies suggested that an intact CST allows pain control but did not discuss the TCT. Our results suggest that the TCT also plays a role in pain reduction by rTMS of the primary motor cortex and that the efficacy of rTMS for patients with CPSP is predictable by fiber tracking.