Suguru Kadowaki

Variability in Response to Quadripulse Stimulation of the Motor Cortex

BACKGROUND Responses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS). OBJECTIVE We assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters. METHODS First, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5-10 min for up to one hour after intervention. RESULTS QPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s. CONCLUSIONS The IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.

Volitional Walking via Upper Limb Muscle-Controlled Stimulation of the Lumbar Locomotor Center in Man

Gait disturbance in individuals with spinal cord lesion is attributed to the interruption of descending pathways to the spinal locomotor center, whereas neural circuits below and above the lesion maintain their functional capability. An artificial neural connection (ANC), which bridges supraspinal centers and locomotor networks in the lumbar spinal cord beyond the lesion site, may restore the functional impairment. To achieve an ANC that sends descending voluntary commands to the lumbar locomotor center and bypasses the thoracic spinal cord, upper limb muscle activity was converted to magnetic stimuli delivered noninvasively over the lumbar vertebra. Healthy participants were able to initiate and terminate walking-like behavior and to control the step cycle through an ANC controlled by volitional upper limb muscle activity. The walking-like behavior stopped just after the ANC was disconnected from the participants even when the participant continued to swing arms. Furthermore, additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in voluntary walking. These results demonstrate that the ANC induces volitionally controlled, walking-like behavior of the legs. This paradigm may be able to compensate for the dysfunction of descending pathways by sending commands to the preserved locomotor center at the lumbar spinal cord and may enable individuals with paraplegia to regain volitionally controlled walking.

Influence of phasic muscle contraction upon the quadripulse stimulation (QPS) aftereffects

OBJECTIVE Contractions of the target muscle influence the aftereffects of repetitive transcranial magnetic stimulation (rTMS). The aim of this paper is to investigate whether or not voluntary hand movement influences the aftereffects of quadripulse stimulation (QPS) on the hand motor area. METHODS Thirteen healthy volunteers participated in this study. After QPS-5 or QPS-50 intervention over the motor hot spot for the right first dorsal interosseous muscle (FDI), the subjects performed voluntary motor tasks (opening-closing right hand movements at 1 Hz for 1 min). We compared the time courses of MEP size between the conditions with and without voluntary movement. RESULTS When the subjects moved their hands immediately after QPS, both QPS-5 and QPS-50 aftereffects were abolished. However, if they moved their hands at 20 min after QPS, the long-term aftereffects were preserved. CONCLUSIONS Voluntary hand movement applied after intervention influences QPS aftereffects, but the magnitude of the influence depends on the delay between QPS and the voluntary movement. SIGNIFICANCE In the plasticity induction experiments, we should always be mindful of the fact that voluntary movement, including the target muscle, seriously influences the induced long-term effects of QPS.

Hemichorea-Hemiballism in a Patient with Temporal-Parietal Lobe Infarction Appearing After Reperfusion by Recombinant Tissue Plasminogen Activator

Hemichorea-hemiballism (HC-HB) is classically associated with stroke lesions in the STN. A large clinical study reported that some other lesions in the basal ganglia, such as in the caudate and putamen, may also cause HC-HB, which is seldom the result of a cortical infarction. We observed transient HC-HB in a patient with a cerebral infarction in the temporal-parietal lobe without any lesions in the basal ganglia including the STN after intravenous recombinant tissue plasminogen activator (rtPA) administration. A 72-year-old right-handed female, who had neither a history of diabetes mellitus nor dopaminergic medication use, was admitted to our hospital because of sudden-onset leftsided hemiparesis. Neurological examination revealed spatial disorientation, conjugate eye deviation to the right, and dysarthria. She had left-sided hemiparesis and sensory disturbance of all modalities. Deep tendon reflexes were exaggerated in the affected limbs. The plantar response was bilaterally flexor. National Institutes of Health Stroke Scale (NIHSS) was 19 points on admission. Blood sample tests were normal except for elevations of brain natriuretic peptide (717 pg/mL) and D-dimer (10.3 lg/mL). Thyroid function was normal, and hyperglycemia was ruled out. Brain MRIs showed acute cerebral infarction in the right temporal-parietal lobe perfused by the middle cerebral artery (MCA; Fig. 1A,B). Electrocardiogram showed atrial fibrillation. The patient was diagnosed as having cardioembolic infarction, and rtPA was administered within 3 hours after onset of symptoms. Nine hours later, her hemiparesis was improved significantly, which was reflected in the NIHSS score of 8 points (11-point decrease). Subsequent to motor improvement, the left hand started to show choreic movements, such as stereotypic pronation and supination, which progressed into ballistic arm movements in a day’s time. Eventually, the left-lower extremity was also involved, confirming HC-HB syndrome (Video 1). Subsequent brain MRIs confirmed no lesions in the basal ganglia, including the STN, and no changes in size of the stroke lesion (Fig. 1C,D). Single-photon emission CT (SPECT) showed an increase of blood flow in the right basal ganglia and hypoperfusion in the affected cortical lesion (Fig. 1E). These involuntary movements persisted and disappeared on the ninth day. She no longer exhibited neurological deficits thereafter. Five months later, follow-up brain MRIs revealed cortical laminar necrosis with atrophic changes in the stroke lesion, but no lesions in the basal ganglia (Fig. 1F). Hyperkinetic involuntary movements accompanied by a pure cortical infarction sparing the basal ganglia are extremely rare. The aforementioned large clinical study reported that only 6 cases of 5,007 consecutive stroke patients had hemichorea (0.12%), and the lesions were located in the MCA territory. In patients with an STN lesion, hyperkinetic disorder can be explained by dysfunction of the basal ganglia in the motor loop: Reduction of the striatopallidal inhibitory network by STN lesions leads to disinhibition of the thalamus and cortex, resulting in hyperkinetic involuntary movements. The mechanism of the cortical HC-HB has yet to be elucidated. A possible hypothesis proposes that interruption of the motor loop projection from the cortex to the basal ganglia by cortical infarctions might induce disparity of the excitatory and inhibitory neural network in the basal ganglia. Mizushima et al. reported HC-HB after a parietal lobe infarction. The brain MRI of this patient showed no basal ganglia lesions, but SPECT revealed hypoperfusion in the basal ganglia, indicating that ischemia of the basal ganglia may lead to functional imbalance and trigger HC-HB. A recent case series study showed 3 HC-HB cases that were associated with cerebral infarctions and reduction of blood perfusion in the frontal and parietal cortices sparing the basal ganglia. The researchers suggested a model of HC-HB induced by cortical lesions in which derangement of the corticocortical

T119. Strength of peripheral nerve stimulation impacts on the magnitude of synaptic plasticity induced at spinal motoneurons

Introduction Paired-associative stimulation (PAS), repeated transcranial magnetic stimulation (TMS) pairing with electrical peripheral nerve stimulation (ES), is one method of synaptic plasticity induction. If these two stimuli are delivered at the timing that descending volleys overlap with peripheral inputs at the spinal motoneurons (SM), long-term potentiation (LTP) like plasticity is induced at the SM synapses (SM-PAS). Here we investigated influences of stimulus intensity of ES on the degree of plasticity. Methods Eight right-handed healthy volunteers participated in this study. Electromyograms were recorded from right first dorsal interosseous muscle (FDI). Peripheral ES was delivered on right ulnar nerve at the wrist. TMS was applied over the left primary motor cortex (M1) hand area, and stimulus intensity was set at 120% resting motor threshold of the right FDI. We measured motor-evoked potentials (MEP) and F-wave latencies in each subject. As for SM-PAS, TMS and ES were delivered at the timing that antidromic volley derived by ES arrives at the postsynaptic terminals 1 ms before an initial descending volley evoked by TMS reaches the presynaptic terminals. A stimulus pairing of TMS with ES was given every 5 s (0.2 Hz) for 15 min (total of 180 pairs). Three different ES intensities were delivered at supramaximal intensity, at three times the sensory threshold (with muscle twitch), and at two times the sensory threshold (without muscle twitch). For evaluating SM synaptic excitability, single-pulse TMS was delivered at cervicomedullary junction level during brief contraction of the right FDI, and cervicomedullary MEP (CMEP) was recorded before and 1 min and every 10 min from 10 to 60 min after the SM-PAS intervention. Results CMEP increased after SM-PAS at supramaximal ES and at three times the sensory threshold, while SM-PAS at two times the sensory threshold induced no CMEP changes. SM-PAS with supramaximal ES was most effective. Conclusion SM-PAS at three times the sensory threshold induces sensory-motor associative plasticity constituted of sensory afferent inputs with multiple corticospinal descending volleys. Supramaximal ES stimulates both sensory afferent fibers and motor neuron axons antidromically, and SM-PAS may induce both sensory afferent and motor antidromic input associative plasticity. Antidromic inputs driven by supramaximal ES may augment associative synaptic plasticity at spinal motoneurons.

A possible role of low regulatory T cells in anti-acetylcholine receptor antibody positive myasthenia gravis after bone marrow transplantation

BackgroundChronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated.Case presentationA 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months. He showed progressive decrement of compound muscle action potential in the deltoid muscle evoked by 3-Hz repetitive nerve stimulation, a positive edrophonium test, and elevated levels of serum anti-acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG. No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes). Administration of prednisolone and tacrolimus was insufficient to alleviate his symptoms; however, the use of rituximab successfully improved his condition.ConclusionsMyasthenic symptoms appeared in the process of tapering prednisolone for the treatment of chronic GVHD, supporting the diagnosis of MG associated with chronic GVHD. The present case proposes a possibility that reduction of Tregs might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy with rituximab is beneficial for treatment of refractory MG and GVHD.

P1064: Phasic muscle contraction influence upon the quadripulse stimulation (QPS) after effects

before and after the exercise on day 1 (T0, T1) and after the exercise on day 5 (T2). Basketball players attended only to T0 and T1. Results: In FCR of the sedentary group (Fig. 1, amplitude ratios, blue: T0, red: T1, green: T2, bars: standard deviations), there were less short latency afferent inhibition and higher facilitation at T1 (statistically significant at ISI 35 and 50 ms). This effect decreased at T2 despite the increased success rate. Basketball players did not show a facilitation as high as that found in the sedentary group. Conclusion: Short term exercises lead to SMI changes which may function in the early phase of gaining the ability. Continued training provided higher success while the electrophysiological changes was decreasing, possibly by the conversion of the learning process into different mechanisms. Exercising already gained abilities do not produce similar SMI changes.