Takufumi Yanagisawa

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.

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.

Neural decoding using gyral and intrasulcal electrocorticograms

Electrocorticography of the primary motor cortex (M1) is a promising tool for controlling a brain-computer interface (BCI). Electrocorticograms (ECoG) of the human M1 within the central sulcus (intrasulcal ECoG) have been rarely examined. In order to evaluate the usefulness of intrasulcal ECoG for BCI, we examined patients with subdural electrodes placed temporarily inside the central sulcus and over the sensorimotor cortex (gyral ECoG). Five patients were asked to perform or imagine two or three classes of simple upper limb movements. Univariate statistical analysis of the results revealed that the intrasulcal ECoG on M1 showed significant variability across movement classes. A support vector machine was used for classification of single-trial ECoG signals to infer movement class (neural decoding). The movement classes were predicted with 80-90% accuracy (chance level: 33% or 50%). To reveal the relative importance of anatomical areas for neural decoding, the decoding performance was compared between gyral and intrasulcal ECoGs. The intrasulcal ECoG on the motor bank showed higher performance than the equally-sized gyral ECoG or the intrasulcal ECoG on the sensory bank. Analysis using a short time window revealed that movement class could be decoded even before movement onset. These results suggest the usefulness of intrasulcal ECoG on M1 to infer upper limb movements and present a promising application for a practical BCI system.

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.

Prediction of three-dimensional arm trajectories based on ECoG signals recorded from human sensorimotor cortex.

Brain-machine interface techniques have been applied in a number of studies to control neuromotor prostheses and for neurorehabilitation in the hopes of providing a means to restore lost motor function. Electrocorticography (ECoG) has seen recent use in this regard because it offers a higher spatiotemporal resolution than non-invasive EEG and is less invasive than intracortical microelectrodes. Although several studies have already succeeded in the inference of computer cursor trajectories and finger flexions using human ECoG signals, precise three-dimensional (3D) trajectory reconstruction for a human limb from ECoG has not yet been achieved. In this study, we predicted 3D arm trajectories in time series from ECoG signals in humans using a novel preprocessing method and a sparse linear regression. Average Pearson’s correlation coefficients and normalized root-mean-square errors between predicted and actual trajectories were 0.44∼0.73 and 0.18∼0.42, respectively, confirming the feasibility of predicting 3D arm trajectories from ECoG. We foresee this method contributing to future advancements in neuroprosthesis and neurorehabilitation technology.

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.

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.

Transiently higher release probability during critical period at thalamocortical synapses in the mouse barrel cortex: relevance to differential short‐term plasticity of AMPA and NMDA EPSCs and possible involvement of silent synapses

Thalamocortical connections undergo remarkable plasticity during the critical period and mounting evidence serves to demonstrate that the activation of silent synapses at postsynaptic sites is an important underlying mechanism in this process. However, relatively little is known about the nature of the presynaptic properties. In the present study, we examined the release probability (Pr) of thalamocortical synaptic terminals on a layer IV neuron in the developing mouse barrel cortex. Using the conventional paired‐pulse ratio (PPR) method, both AMPA and NMDA receptor‐mediated PPR were observed during development. We found that the NMDA PPR increased gradually (thus, a reduction in Pr) from postnatal day (P)4 to P22 but, unexpectedly, the AMPA PPR exhibited a simultaneous decrease. We then used an additional method for assessing release probability, the observation of a progressive block of NMDA receptor‐mediated EPSCs using MK‐801. With this method, we were able to identify two classes of terminals with high or low probabilities of release. Interestingly, the higher release showed a reduction in probability during the critical period, consistent with the NMDA PPR results. We confirmed that the discrepancy between the NMDA and the AMPA PPR results was due to the existence of silent, or NMDA‐only, synapses, as suggested in previous literature. By analysing the correlation between the NMDA or AMPA PPR and the PPR discrepancy, we discuss the hypothesis that the terminals with transiently higher probability of release were found preferentially on silent synapses. Our results suggest that these presynaptic sites may also have an active role in plasticity by working concomitantly with postsynaptic sites during the critical period.

Frequency-dependent spatiotemporal distribution of cerebral oscillatory changes during silent reading: A magnetoencephalograhic group analysis

The frequency profiles and time courses of oscillatory changes when reading words are not fully understood, although there have been many reports that oscillatory dynamics reflect local brain function. In order to clarify oscillatory dynamics, we investigated the frequency and spatiotemporal distributions of neuromagnetic activities during silent reading of words in 23 healthy subjects. Individual data were divided into the following frequency bands: theta (5-8 Hz), alpha (8-13 Hz), beta (13-25 Hz), low gamma (25-50 Hz), and high gamma (50-100 Hz), and were analyzed by synthetic aperture magnetometry (SAM). The time window was consecutively moved in steps of 50 ms. Group analysis was performed to delineate common areas of brain activation. A transient power increase in the theta band occurred first in the bilateral occipital cortices, and then rapidly propagated to the left temporo-occipital areas, left inferior and middle frontal gyri, bilateral medial prefrontal cortices, and finally to the left anterior temporal cortices, which possibly reflects a serial cognitive process. This serial propagation of the transient power increase in the theta band was followed by sustained power decreases in the alpha, beta and low gamma bands. These results suggest that the transient power increase in the theta bands may be associated with priming and propagation of local activities, while sustained power decreases in the alpha, beta and low gamma bands reflect parallel neural processes related to silent reading words. Our results showed a relationship between frequency bands of oscillatory changes and locations. This may have implications in the relationship between frequency bands and functions.

Use of fractional anisotropy for determination of the cut-off value in 11C-methionine positron emission tomography for glioma.

Multimodal imaging is one of the necessary steps in the treatment of malignant brain tumors, and use of magnetic resonance imaging (MRI) and positron emission tomography (PET) are the current gold standard technique for the morphological and biological assessment of malignant brain tumors. In addition, fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) and 11C-methionine PET are useful to determine the tumor border at the tumor and white matter interface. Although there is no question of their value, a universally accepted cut-off value to discriminate normal and abnormal tissue has not been established. In this study we attempted to calculate and determine the cut-off values in FA and 11C-methionine PET that will allow delineation of the tumor border at the tumor and white matter interface by combining these two modalities. We were able to determine individual cut-off values for 11 patients, and then found an average cut-off value in the T/N ratio of 11C-methionine PET of 1.27 and in FA of 0.26, values similar to those previously confirmed by histological study. Moreover, reconstructing images delineating the tumor border was possible combining these two imaging modalities. We propose that the combined analysis of DTI and 11C-methionine PET has the potential to improve tumor border imaging in glioma patients, providing important information for establishing neurosurgical strategies.