Tatsuya Mima

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.

Electroencephalographic analysis of cortico-muscular coherence: reference effect, volume conduction and generator mechanism

OBJECTIVE To measure the synchrony between cortical and muscle oscillatory activities, the coherence estimate between EEG and EMG was computed. METHODS The multichannel electroencephalogram (EEG) and electromyogram (EMG) of the right abductor pollicis brevis muscle were recorded in 5 normal volunteers. Various types of EEG derivation methods were systematically compared to establish a standard method to study cortico-muscular coupling. RESULTS The use of a reference-free EEG derivation (current source density) greatly improved cortico-muscular coherence. In all subjects, EEGs over the left sensorimotor cortex were coherent with EMG (mean peak frequency: 18.7 Hz, mean highest coherence: 0.124). The time lag from cortex to muscle in 14-50 Hz was 14.3 ms. EEG source derivation revealed that both radial and tangential generators in the precentral cortex might contribute to this phenomenon. In the EEG signals using common average reference, an artifactual coherence peak over the medial frontal area was observed, which might largely be explained by volume conduction from the primary sensorimotor cortex. CONCLUSIONS We conclude that the current source density or its approximation is preferable to estimate the cortico-muscular coherence and that the interpretation of such coherence using referenced EEGs should be taken with care.

Altered plasticity of the human motor cortex in Parkinson's disease

Interventional paired associative stimulation (IPAS) to the contralateral peripheral nerve and cerebral cortex can enhance the primary motor cortex (M1) excitability with two synchronously arriving inputs. This study investigated whether dopamine contributed to the associative long‐term potentiation–like effect in the M1 in Parkinsons disease (PD) patients. Eighteen right‐handed PD patients and 11 right‐handed age‐matched healthy volunteers were studied. All patients were studied after 12 hours off medication with levodopa replacement (PD‐off). Ten patients were also evaluated after medication (PD‐on). The IPAS comprised a single electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 milliseconds (240 paired stimuli every 5 seconds for 20 minutes). The motor‐evoked potential amplitude in the right abductor pollicis brevis muscle was increased by IPAS in healthy volunteers, but not in PD patients. IPAS did not affect the motor‐evoked potential amplitude in the left abductor pollicis brevis. The ratio of the motor‐evoked potential amplitude before and after IPAS in PD‐off patients increased after dopamine replacement. Thus, dopamine might modulate cortical plasticity in the human M1, which could be related to higher order motor control, including motor learning. Ann Neurol 2006

Functional localization of pain perception in the human brain studied by PET.

TO elucidate the functional localization and somatotopic organization of pain perception in the human cerebral cortex, we studied the regional cerebral blood flow using positron emission tomography during selective painful stimulation in six normal subjects. Response to a painful stimulus was elicited using a special CO2 laser, which selectively activates nociceptive receptors, to the hand and foot. Multiple brain areas, including bilateral secondary somatosensory cortices (SII) and insula, and the frontal lobe and thalamus contralateral to the stimulus side, were found to be involved in the response to painful stimulation. While our data indicate that the bilateral SII play an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human SII or insula.

Functional coupling of human right and left cortical motor areas demonstrated with partial coherence analysis

Although a linear correlation between oscillatory activities in the right and left motor cortices during movements has been shown in monkeys, there has been a debate whether scalp-recorded EEG coherence in human reflects a similar association. By applying partial coherence analysis, we demonstrated that interhemispheric coherence during movements cannot be explained by contamination from the occipital alpha rhythm or common reference signal. A significant increase of net interhemispheric communication in the beta1 band was shown during movements. We propose that the partial coherence method can be a useful tool to measure cortico-cortical functional coupling reliably.

Force level modulates human cortical oscillatory activities

We studied the relationship between cortical and muscular oscillatory activities and muscular force level during a tonic contraction task using electroencephalography (EEG). Within the weak to moderate force level, the normalized power in the alpha band in the contralateral sensorimotor areas was inversely linearly correlated with the force. Cortical-muscular coherence was observed in the beta band and its magnitude was not affected by the force. In contrast, during strong contractions, EEG power in the gamma band increased and was partly correlated with the Piper rhythm in the electromyogram. Our results show that the multiple oscillatory activities in the cortex are correlated with the force level in different ways. Cortical gamma band oscillation may reflect both focused attention and the efferent drive to the muscle during very strong tonic contraction.

Effects of aging on the human motor cortical plasticity studied by paired associative stimulation

OBJECTIVE To test whether the normal aging itself may change the cortical plasticity in human. METHODS Motor-evoked potentials (MEPs) were measured from 48 right-handed healthy volunteers (age 21-79) before and after the paired associative stimulation (PAS), comprising a single electric stimulus to the right median nerve at wrist and subsequent transcranial magnetic stimulation (TMS) of the left primary motor cortex. RESULTS The magnitude of MEP increased by PAS in the young and middle but not in the elderly and its change was negatively correlated with the age. CONCLUSIONS These results suggest that the human M1 shows age-dependent reduction of cortical plasticity. SIGNIFICANCE The reduction of the M1 plasticity may be caused by the attenuated responsiveness of intracortical circuits in the M1 and/or disrupted sensorimotor integration within basal ganglia-thalamocortical loop.

Human Motor Plasticity Induced by Mirror Visual Feedback

The clinical use of mirror visual feedback (MVF) was initially introduced to alleviate phantom pain, and has since been applied to the improvement of hemiparesis following stroke. However, it is not known whether MVF can restore motor function by producing plastic changes in the human primary motor cortex (M1). Here, we used transcranial magnetic stimulation to test whether M1 plasticity is a physiological substrate of MVF-induced motor behavioral improvement. MVF intervention in normal volunteers using a mirror box improved motor behavior and enhanced excitatory functions of the M1. Moreover, behavioral and physiological measures of MVF-induced changes were positively correlated with each other. Improved motor performance occurred after observation of a simple action, but not after repetitive motor training of the nontarget hand without MVF, suggesting the crucial importance of visual feedback. The beneficial effects of MVF were disrupted by continuous theta burst stimulation (cTBS) over the M1, but not the control site in the occipital cortex. However, MVF following cTBS could further improve the motor functions. Our findings indicate that M1 plasticity, especially in its excitatory connections, is an essential component of MVF-based therapies.

Information flow from the sensorimotor cortex to muscle in humans.

OBJECTIVES To investigate the physiologic mechanism of human electroencephalogram-electromyogram (EEG-EMG) coherence, the directed transfer function (DTF) based on a multivariate autoregressive (MVAR) model was computed. METHODS Fifty-six channel EEG and EMG of the right abductor pollicis brevis muscle during a weak tonic contraction were recorded in 6 normal volunteers. The EEG over the left sensorimotor area and the rectified EMG were used to compute coherence and DTF. RESULTS EEG-EMG coherence was observed at the peak frequency of 15-29 Hz (mean 18.5 Hz). The peak frequency of DTF from EEG to EMG was 12-27 Hz (mean 17.8 Hz). DTF from EEG to EMG was significantly larger than that from EMG to EEG at 19-30 and 45-50 Hz (P<0.05). CONCLUSIONS The present findings suggest that the EEG-EMG coupling mechanism for the 19 Hz or higher frequency might differ from that for the lower frequency. Directional information flow from EEG to EMG in the former frequency range likely reflects the motor control command. The finding of the directional information flow from EEG to EMG within the gamma band indicates that 40 Hz EEG-EMG coherence is not specific to the muscle Piper rhythm which is seen only with strong contraction.

Disordered plasticity in the primary somatosensory cortex in focal hand dystonia

Interventional paired associative stimulation (PAS) can induce plasticity in the cortex, and this plasticity was previously shown to be disordered in the primary motor cortex in focal hand dystonia (FHD). This study aimed to test whether associative plasticity is abnormal in the primary somatosensory cortex (S1) in FHD and whether PAS modulates excitatory or inhibitory interneurons within the cortex. Ten FHD patients and 10 healthy volunteers were studied. We investigated the changes in single- and double-pulse somatosensory-evoked potentials before and after PAS, which consisted of peripheral electrical nerve stimulation and subsequent transcranial magnetic stimulation over S1. Four sessions of somatosensory-evoked potentials recordings were performed: before PAS, and immediately, 15 and 30 min after PAS. We compared the time course of the somatosensory-evoked potentials between the FHD and healthy groups. In the single-pulse condition, the P27 amplitudes were significantly higher in FHD immediately after PAS than before PAS, while no changes were observed in healthy subjects. In the double-pulse condition, significant differences in the suppression ratio of P27 were found immediately after and 15 min after PAS, while there were no significant differences in healthy subjects. The P27 suppression tended to normalize toward the level of the healthy volunteer group. In FHD, PAS transiently induced an abnormal increase in excitability in S1. In addition, intracortical inhibition in S1 was found to increase as well. This abnormal plasticity of the intracortical neurons in S1 may contribute to the pathophysiology of dystonia.