Tetsu Goto

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.

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.

Regulation of Motor Representation by Phase–Amplitude Coupling in the Sensorimotor Cortex

High-γ amplitude (80–150 Hz) represents motor information, such as movement types, on the sensorimotor cortex. In several cortical areas, high-γ amplitudes are coupled with low-frequency phases, e.g., α and θ (phase–amplitude coupling, PAC). However, such coupling has not been studied in the sensorimotor cortex; thus, its potential functional role has yet to be explored. We investigated PAC of high-γ amplitude in the sensorimotor cortex during waiting for and the execution of movements using electrocorticographic (ECoG) recordings in humans. ECoG signals were recorded from the sensorimotor cortices of 4 epilepsy patients while they performed three different hand movements. A subset of electrodes showed high-γ activity selective to movement type around the timing of motor execution, while the same electrodes showed nonselective high-γ activity during the waiting period (>2 s before execution). Cross frequency coupling analysis revealed that the high-γ amplitude during waiting was strongly coupled with the α phase (10–14 Hz) at the electrodes with movement-selective high-γ amplitudes during execution. This coupling constituted the high-γ amplitude peaking around the trough of the α oscillation, and its strength and phase were not predictive of movement type. As the coupling attenuated toward the timing of motor execution, the high-γ amplitude appeared to be released from the α phase to build a motor representation with phase-independent activity. Our results suggest that PAC modulates motor representation in the sensorimotor cortex by holding and releasing high-γ activity in movement-selective cortical regions.

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O PET study

Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H(2)(15)O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H(2)(15)O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76.1+/-25.2 before SCS to 40.6+/-4.5 after SCS (mean+/-SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS.

11C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: A stereotactic image-histology comparison

(11)C-methionine positron emission tomography ((11)C-methionine PET) provides accurate detection of brain tumors. Several reports have analyzed the correlation between uptake of (11)C-methionine and Ki-67 index or microvessel density non-stereotactically and suggested that (11)C-methionine uptake reflects both proliferation potential and angiogenic capability in gliomas. As gliomas possess heterogeneous histological architecture, non-stereotactic comparison of the histology and (11)C-methionine PET image may not be accurate. In the present study, the correlation between (11)C-methionine uptake and cell or microvessel density was analyzed using histological specimens obtained by stereotactic biopsy, and an exact local comparison of (11)C-methionine PET image and histological specimens was conducted. The tumor/normal tissue (T/N) ratio of (11)C-methionine positron emission tomography was found to correlate better with cell density (R=0.747, p=0.000042) and Ki-67 index (R=0.675, p=0.00041) than with microvessel density (R=0.467, p=0.025) in a histological comparison using a stereotactic image. Furthermore, multiple linear regression analysis revealed that cell density was the key determinant for predicting (11)C-methionine level while microvessel density was not. These results suggest that cell density contributes more to (11)C-methionine uptake than microvessel density in glioma tissues and that the previously reported correlation of (11)C-methionine uptake and microvessel density in glioma patients requires reevaluation.

Diffusion tensor-based tumor infiltration index cannot discriminate vasogenic edema from tumor-infiltrated edema

Diffusion tensor imaging (DTI) by magnetic resonance imaging (MRI) is now used not only for delineating white matter fiber tracts, but also for assessing the histological characteristics of pathological tissues. Among these uses, predicting the extent or existence of tumor cell invasion into white matter by DTI is under extensive investigation. The previously reported tumor infiltration index (TII) holds great potential for the discrimination of pure vasogenic edema from tumor-infiltrated edema. However, conflicting data are being reported questioning the clinical value of TII. The present investigation reevaluated the utility of TII in patients with meningioma or glioma. We found that TII was unable to discriminate vasogenic from tumor-infiltrated edema. Conversely, detailed voxel-by-voxel comparison of TII and 11C-methionie PET in the T2-hyperintense area of gliomas showed that TII and 11C-methionie PET has a positive correlation, suggesting that, although TII is unable to discriminate the cause of edema, the extent of tumor cell invasion into white matter is depicted in gliomas by TII. These data suggest that TII involves both vasogenic and tumor-infiltrated factors, rather than only a single factor. A more intensive investigation is required to reach a complete understanding of TII.

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease.

&NA; Patients with Parkinson’s disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN‐DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN‐DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold‐induced and heat‐induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS‐on mode when compared with the DBS‐off mode (P < .001), whereas the CSTs and WSTs of patients in the DBS‐off mode were significantly greater than those of healthy control subjects (P < .02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P < .02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN‐DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease‐related brain network abnormalities. Quantitative evaluation on the effect of deep brain stimulation of the subthalamic nucleus on temperature sensation and pain suggested that it could improve impaired temperature sensation in patients with Parkinson’s disease.

Differential responses of primary auditory cortex in autistic spectrum disorder with auditory hypersensitivity.

The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were statistically larger than those in the other two groups. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it.