R. Hanajima

Preferential activation of different I waves by transcranial magnetic stimulation with a figure-of-eight-shaped coil.

Transcranial magnetic stimulation (TMS) over the human primary motor cortex (M1) evokes motor responses in the contralateral limb muscles. The latencies and amplitudes of those responses depend on the direction of induced current in the brain by the stimuli (Mills et al. 1992, Werhahn et al. 1994). This observation suggests that different neural elements might be activated by the differently directed induced currents. Using a figure-of-eight-shaped coil, which induces current with a certain direction, we analyzed the effect of direction of stimulating current on the latencies of responses to TMS in normal subjects. The latencies were measured from surface electromyographic responses of the first dorsal interosseous muscles and the peaks in the peristimulus time histograms (PSTHs) of single motor units from the same muscles. The coil was placed over the M1, with eight different directions each separated by 45°. Stimulus intensity was adjusted just above the motor threshold while subjects made a weak tonic voluntary contraction, so that we can analyse the most readily elicited descending volley in the pyramidal tracts. In most subjects, TMS with medially and anteriorly directed current in the brain produced responses or a peak that occurred some 1.5 ms later than those to anodal electrical stimulation. In contrast, TMS with laterally and posteriorly directed current produced responses or a peak that occurred about 4.5 ms later. There was a single peak in most of PSTHs under the above stimulation condition, whereas there were occasionally two peaks under the transitional current directions between the above two groups. These results suggest that TMS with medially and anteriorly directed current in the brain readily elicits I1 waves, whereas that with laterally and posteriorly directed current preferentially elicits I3 waves. Functional magnetic resonance imaging studies indicated that this direction was related to the course of the central sulcus. TMS with induced current flowing forward relative to the central sulcus preferentially elicited I1 waves and that flowing backward elicited I3 waves. Our finding of the dependence of preferentially activated I waves on the current direction in the brain suggests that different sets of cortical neurons are responsible for different I waves, and are contrarily oriented. The present method using a figure-of-eight-shaped coil must enable us to study physiological characteristics of each I wave separately and, possibly, analyse different neural elements in M1, since it activates a certain I wave selectively without D waves or other I waves.

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex

OBJECTIVES To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.

Interhemispheric interaction between the hand motor areas in patients with cortical myoclonus.

OBJECTIVE To study interhemispheric interaction between the hand motor areas of both hemispheres through the corpus callosum in myoclonus epilepsy. SUBJECTS Five patients with benign myoclonus epilepsy and ten age matched normal volunteers. METHODS We studied effects of a medially directed conditioning stimulus over the right hand motor area on responses in the right first dorsal interosseous muscle to a posteriorly directed test stimulus over the left hand motor area. RESULTS In normal subjects, inhibition was evoked at interstimulus intervals (ISIs) of 8-20ms (late inhibition). In contrast, facilitation occurred in patients at ISIs of 4-6ms (early facilitation) with no late inhibition. CONCLUSIONS The lack of late inhibition in the patients is consistent with the idea that cortical inhibitory interneurones are affected in myoclonus epilepsy. We propose that this releases interhemispheric facilitation from powerful surround inhibition. The consequence is a predominant early facilitation between the hemispheres in patients with myoclonus epilepsy.

Physiological analyses of a patient with extreme widening of Virchow-Robin spaces.

We report on a 60-year-old woman with extreme widening of Virchow-Robin spaces who showed neither neurological symptoms nor signs. Magnetic resonance imagings (MRIs) of her brain disclosed multiple abnormalities located along the perforating medullary arteries in the white matter. Central sensory and motor conduction studies (sensory evoked potentials (SEPs) and magnetic stimulation) showed no conduction delays and several modulatory inputs normally influenced the motor and sensory cortical excitability, as expected from clinical features. These physiological analyses confirmed the functional integrity of the central sensory and motor systems, even though imaging studies showed seemingly serious abnormalities.

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans.

OBJECTIVE Quadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1). METHODS One burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs). RESULTS QPS-5 over M1 or dPMC enhanced the P25-N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs. CONCLUSIONS QPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations. SIGNIFICANCE QPSs induced heterotopic LTP or LTD-like cortical excitability changes.

Intracortical inhibition of the motor cortex in Segawa disease (DYT5)

Background: Segawa disease (autosomal dominant guanosine triphosphate cyclohydrolase I [GTP-I] deficiency, DYT5) is a hereditary dopa-responsive generalized dystonia. Objective: To investigate the pathophysiologic mechanisms for dystonia in Segawa disease, we studied intracortical inhibition of the primary motor cortex in patients with Segawa disease. Methods: We studied 9 patients with Segawa disease (8 genetically confirmed patients and 1 with abnormally low GTP-I activity) and 12 age-matched normal control subjects. We studied the active motor threshold (AMT) using single pulse transcranial magnetic stimulation (TMS) and the short-interval intracortical inhibition (SICI) of the motor cortex using the previously reported paired pulse TMS method. Responses were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Results: The AMT was not significantly different between the patients and normal subjects. For both studied muscles, in Segawa disease, normal amount of SICI was evoked at interstimulus intervals (ISIs) of 1 to 4 msec even though they had dystonia in those muscles. Conclusion: Normal SICI of the motor cortex in Segawa disease stands in remarkable contrast to the previously reported reduction of SICI in focal dystonia. This suggests that the gamma-aminobutyric acid A system of the motor cortex is intact in Segawa disease. The pathophysiologic mechanisms for dystonia must be partly different between Segawa disease and focal dystonia.

Somatosensory-evoked potential modulation by quadripulse transcranial magnetic stimulation in patients with benign myoclonus epilepsy

OBJECTIVE In patients with benign myoclonus epilepsy (ME), giant sensory-evoked potential (SEP) reflects the hyperexcitability of the sensory cortex. The aim of this study was to compare the effect of quadripulse transcranial magnetic stimulation (QPS) on the median nerve SEP between ME patients and healthy subjects. METHODS Ten healthy volunteers and six ME patients with giant SEP participated in this study. QPSs at interpulse intervals (IPIs) of 5, 30, 50, 100, 500 and 1250 ms were applied over the left primary motor cortex (M1) for 30 min. The peak-to-peak amplitudes of N20 to P25 (N20-P25) and P25 to N33 (P25-N33) components were measured at the left somatosensory cortex. RESULTS In healthy participants, the P25-N33 was bidirectionally modulated by QPS over M1, following the Bienenstock-Cooper-Munro (BCM) theory. The N20-P25 was not affected by any QPSs. In ME patients, the giant P25-N33 was potentiated after any QPSs. Furthermore, the N20-P25 was also potentiated after QPS at IPIs of 5, 30, 50 100 or 500 ms. CONCLUSIONS In ME patients, the cascade for long-term depression-like effects may be impaired. SIGNIFICANCE The giant SEP was furthermore enhanced by QPS.

P224: Cauda equina conduction time in GBS, CIDP, and MMN

Introduction: To investigate the conductions of proximal and distal parts of peripheral nerves in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and multifocal motor neuropathy (MMN), we measured cauda equina conduction time (CECT) and motor conduction velocity (MCV). Methods: Patients were 12 GBS (8 axonal and 4 demyelinating types), 14 CIDP, and 5 MMN patients. Compound muscle action potentials (CMAPs) were recorded from the abductor hallucis muscle. To measure MCV, electrical stimulation was conducted. To obtain CECT, magnetic stimulation was performed using a MATS coil (magnetic augmented translumbosacral stimulation coil). Results: CECT was normal in all axonal GBS patients but prolonged in all demyelinating GBS patients, whereas MCV was normal in all GBS patients. CECT was prolonged in 12 CIDP patients (85.7%), whereas MCV was delayed in 5 CIDP patients (35.7%). Both CECT and MCV were normal in all MMN patients. Conclusions: CECT is frequently prolonged in demyelinating GBS and CIDP, whereas it is usually normal in axonal GBS and MMN. MATS coil stimulation method can detect the conduction delay of cauda equina in some types of demyelinating polyneuropathy.

P 205. Cortico-conus motor conduction time (CCCT)

Objective To measure the conduction time from the motor cortex to the conus medullaris (cortico-conus motor conduction time, CCCT) for leg muscles using magnetic stimulation. Methods Motor evoked potentials (MEPs) were recorded from right tibialis anterior muscle in 100 healthy volunteers. To activate spinal nerves at the most proximal cauda equina level or at the conus medullaris level, magnetic stimulation was performed using a MATS coil. Transcranial magnetic stimulation of the motor cortex was also conducted to measure the cortical latency for the target muscle. To obtain the CCCT, the latency of MEPs to conus stimulation (conus latency) was subtracted from the cortical latency. Results MATS coil stimulation evoked reproducible MEPs in all subjects, yielding CCCT data for all studied tibialis anterior muscles. Conclusions MATS coil stimulation provides CCCT data for healthy subjects. This novel method is useful for evaluation of corticospinal tract conduction for leg muscles because no peripheral component affects the CCCT.

PTMS52 Normal SICI in Parkinson's disease: SICI using anterior posterior directed induced currents in the brain

phosphocholine [PCho] + glycerophosphocholine [GPC]) were measured bilaterally in primary sensorimotor cortex, lentiform nucleus, and the occipital region before and after 5 Hz TMS over the dominant motor cortex. Sixteen patients with upper limb primary dystonia were studied and compared to healthy volunteers. Results: At baseline, in patients with writer’s cramp, there was a higher GABA concentration bilaterally in the motor cortex as compared with controls. In controls but not patients, 5 Hz TMS over the left motor cortex induced an in situ-change in metabolite concentrations that depended on baseline concentration levels; i.e., increase for lower baseline levels and decrease for higher. Effects in basal ganglia were less consistent. Greater concentration decreases in NAA, mIns, and tCho were observed in the motor cortex of the patients after TMS. Conclusion: Together with previous results, our study points to a dysfunction of the GABAergic inhibitory system in dystonia. TMS-induced changes of NAA, mIns and tCho are interpreted in view of the maladaptive plasticity and abnormal membrane-related protein previously suggested in dystonia.