Keiichiro Shindo

Effects of neurofeedback training with an electroencephalogram-based brain-computer interface for hand paralysis in patients with chronic stroke: a preliminary case series study.

OBJECTIVEnTo explore the effectiveness of neurorehabilitative training using an electroencephalogram-based brain- computer interface for hand paralysis following stroke.nnnDESIGNnA case series study.nnnSUBJECTSnEight outpatients with chronic stroke demonstrating moderate to severe hemiparesis.nnnMETHODSnBased on analysis of volitionally decreased amplitudes of sensory motor rhythm during motor imagery involving extending the affected fingers, real-time visual feedback was provided. After successful motor imagery, a mechanical orthosis partially extended the fingers. Brain-computer interface interventions were carried out once or twice a week for a period of 4-7 months, and clinical and neurophysiological examinations pre- and post-intervention were compared.nnnRESULTSnNew voluntary electromyographic activity was measured in the affected finger extensors in 4 cases who had little or no muscle activity before the training, and the other participants exhibited improvement in finger function. Significantly greater suppression of the sensory motor rhythm over both hemispheres was observed during motor imagery. Transcranial magnetic stimulation showed increased cortical excitability in the damaged hemisphere. Success rates of brain-computer interface training tended to increase as the session progressed in 4 cases.nnnCONCLUSIONnBrain-computer interface training appears to have yielded some improvement in motor function and brain plasticity. Further controlled research is needed to clarify the role of the brain-computer interface system.

Long-term effect of low-frequency repetitive transcranial magnetic stimulation over the unaffected posterior parietal cortex in patients with unilateral spatial neglect.

OBJECTIVEnTo explore long-term effects on unilateral spatial neglect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected posterior parietal cortex.nnnDESIGNnUncontrolled pilot study.nnnSUBJECTSnTwo chronic-phase patients with left-sided unilateral spatial neglect from cerebral infarction.nnnMETHODSnSix rTMS sessions were undertaken for 2 weeks. Each session included 900 stimuli applied over P5 at an intensity of 95% motor thresholds and a frequency of 0.9 Hz. The Behavioural Inattention Test, either the Mini-Mental State Examination or the Revised Hasegawa Dementia Scale, Brunnstrom Recovery Stage, and Barthel Index were evaluated at 2-week intervals until 6 weeks after rTMS sessions. Single-photon emission computed tomography was performed 2 weeks before and after rTMS.nnnRESULTSnBehavioural Inattention Test scores improved remarkably, especially from 2 to 4 weeks after rTMS sessions. At 6 weeks, Behavioural Inattention Test scores still remained above pre-rTMS levels. Other clinical evaluations as well as single-photon emission computed tomography showed no significant change during the study.nnnCONCLUSIONnIn this small pilot study, low-frequency rTMS over the unaffected posterior parietal cortex decreased unilateral spatial neglect for at least 6 weeks.

Diffusion tensor imaging fiber tractography for evaluating diffuse axonal injury.

Patients with Diffuse axonal injury (DAI) frequently exhibit cognitive disorders chronically. Radiologic recognition of DAI can help understand the clinical syndrome and to make treatment decisions. However, CT and conventional MRI are often normal or demonstrate lesions that are poorly related to the cognitive disorders. Recently, diffusion tensor imaging (DTI) fiber tractography has been shown to be useful in detecting various types of white matter damage. The aim of this study was to evaluate the feasibility of using DTI fiber tractography to detect lesions in DAI patients, and to correlate the DAI lesions with the cognitive disorders. We investigated two patients with chronic DAI. Both had impaired intelligence, as well as attention and memory disorders that restricted their activities of daily living. In both patients, DTI fiber tractography revealed interruption of the white matter fibers in the corpus collosum and the fornix, while no lesions were found on conventional MRI. The interruption of the fornix which involves the circuit of Papez potentially correlates with the memory disorder. Therefore, DTI fiber tractography may be a useful technique for the evaluation of DAI patients with cognitive disorders.

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

OBJECTIVEnBrain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design.nnnMETHODSnA 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram.nnnRESULTSnThe subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed.nnnCONCLUSIONnThese results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Brain-computer interface training combined with transcranial direct current stimulation in patients with chronic severe hemiparesis: Proof of concept study.

OBJECTIVEnBrain-computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain-computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain-computer interface training in patients with severe hemiparesis.nnnSUBJECTSnEighteen patients with chronic stroke.nnnDESIGNnA non-randomized controlled study.nnnMETHODSnSubjects were divided between a brain-computer interface group and a tDCS- brain-computer interface group and participated in a 10-day brain-computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain-computer interface group received anodal tDCS before brain-computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention.nnnRESULTSnEvent-related desynchronization was significantly increased in the tDCS- brain-computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCS-brain-computer interface group.nnnCONCLUSIONnAnodal tDCS can be a conditioning tool for brain-computer interface training in patients with severe hemiparetic stroke.

Transcranial magnetic stimulation synchronized with maximal movement effort of the hemiplegic hand after stroke: a double-blinded controlled pilot study.

OBJECTIVEnThe aim of this study was to evaluate the effects of transcranial magnetic stimulation synchronized with maximal effort to make a target movement in patients with chronic hemiplegia involving the hand.nnnDESIGNnNon-randomized double-blinded controlled trial.nnnSUBJECTSnNine chronic patients with hemiplegia who were unable to fully extend the affected fingers following stroke.nnnMETHODSnPatients were assigned to receive 100 pulses of active or sham transcranial magnetic stimulation of the affected hemisphere per session. Each active or sham pulse was delivered during maximal effort at thumb and finger extension as a target movement. A blinded rater assessed stroke impairments at baseline, immediately after, and one week after 4 weekly transcranial magnetic stimulation sessions. Motor evoked potential amplitudes were measured at each session.nnnRESULTSnAll sessions were completed without adverse effects. Immediately after the fourth transcranial magnetic stimulation session, 4 of 5 patients in the active transcranial magnetic stimulation group (80%) had either reduced wrist flexor spasticity or improved manual performance; no such change occurred in the sham group (Fishers exact test, p < 0.05). Effects persisted one week later. In the active transcranial magnetic stimulation group, 3 patients who showed an increase in motor evoked potential amplitudes all had improvement in clinical assessments.nnnCONCLUSIONnTranscranial magnetic stimulation synchronized with maximum effort to make a target movement improved hand motor function in patients with chronic hemiplegia.

P247: Brain-machine interface training combined with transcranial direct current stimulation in patients with chronic severe hemiparesis: proof of concept study

Objective: Brain–computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain–computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain–computer interface training in patients with severe hemiparesis. Subjects: Eighteen patients with chronic stroke. Design: A non-randomized controlled study. Methods: Subjects were divided between a brain–computer interface group and a tDCS-brain–computer interface group and participated in a 10-day brain–computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain–computer interface group received anodal tDCS before brain–computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention. Results: Event-related desynchronization was significantly increased in the tDCS- brain–computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCSbrain–computer interface group. Conclusion: Anodal tDCS can be a conditioning tool for brain–computer interface training in patients with severe hemiparetic stroke.

P281: Modulation of cortical activity after anodal transcranial direct current stimulation during motor task: an fMRI study

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S123 pauses) and different c-tDCS durations (22 vs. 9 min), to evaluate if and how these parameters may alter its effects. Methods: 1.5mA c-tDCS was delivered by a battery-driven stimulator through an active electrode applied on primary visual cortex (16 cm2), and a reference electrode on the right arm (60 cm2). 82 subjects executed an orientation discrimination task (ODT) in a between-subjects design. They had to decide whether the presented stimulus was tilted clockwise or counterclockwise relative to the previously presented one. We measured the percentage of accuracy (d’ values). Results: rmANOVAs showed an improvement of the performance when ctDCS was applied before the task whereas with online c-tDCS performance was similar to sham. The presence of pauses during c-tDCS and a different duration of the stimulation did not modify the facilitatory induced effect. Conclusions: We demonstrated that not necessarily c-tDCS induce behavioural inhibition, but the effects should be considered in relation to the timing of application and the executed task. The same protocol of “neuroplasticity induction” can provoke different effects depending on the excitability level of the stimulated neurons. We speculate that offline c-tDCS could induce metaplasticity mechanisms functional to obtain an “optimal” neural activation when consequently the cortical area is involved in a specific task. P280 Effects of different repetitive transcranial magnetic stimulation treatments and the role of attentional bias in complex focal hand dystonia: a case-report A. Salatino1, G. Mazzeo1, M. Nobili2, R. Ricci1 1University of Turin, Department of Psychology, Turin, Italy; 2Koelliker Hospital, Unit of Neurology, Turin, Italy Question: Focal hand dystonia (FHD) is a movement disorder characterized by involuntary muscle contraction, causing abnormal postures. Its symptoms are associated with deficient cortical inhibition. Previous studies suggest that inhibitory low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) over contralateral premotor cortex (PMC) might ameliorate FHD, although no clear evidence of significant improvement has been shown. In this study we investigated the effects of different rTMS protocols on complex FHD of the right hand and associated symptoms in a 41-year-old man. Methods: Two different experiments were conducted. In experiment 1, the patient underwent eight daily sessions of rTMS over left PMC. In experiment 2, in order to investigate the role of rightward attentional bias and the effects of lower doses of stimulation we compared the effectiveness of a weekly three days treatment over PMC with a three days treatment over left PPC (Posterior Parietal Cortex). RTMS over left Occipital cortex and sham stimulation over PPC constituted two control conditions. Clinical and behavioral evaluation comprised the patient’s self-estimation of dystonic symptoms, handwriting, finger tapping, and the use of everyday objects. In experiment 2, a line bisection task was also administered. Results: Taken together the findings of the experiments suggest that: 1) lower doses of rTMS over PMC, more distributed in time, may induce better clinical outcomes than higher doses; 2) the rightward attentional bias played a role in this patient’s FHD and was improved by rTMS over PPC; 3) rTMS over PPC induced longer term beneficial effects than rTMS over PMC. Conclusions: Our findings suggest that both PMC and PPC represent effective sites for rTMS treatment of FDH. Future double-blind placebocontrolled studies on groups of patients are needed to further explore the differential role played by the two sites in the pathophysiology of FHD and optimal doses of stimulation. P281 Modulation of cortical activity after anodal transcranial direct current stimulation during motor task: an fMRI study K. Shindo1,2,3, T. Ono2,4, Y. Kasashima-Shindo1,3, H. Ebata2, M. Liu1 1Keio University School of Medicine, Department of Rehabilitation Medicine, Tokyo, Japan; 2Saiseikai Kanagawa Prefecture Hospital, Department of Rehabilitation Medicine, Yokohama, Japan; 3Danish Research Center for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; 4Keio University Faculty of Science and Technology, Department of Biosciences and Informatics, Yokohama, Japan Question: It is known that offline anodal transcranial direct current stimulation (AtDCS) increases cortical activation by motor task. However, it is still unclear how AtDCS during motor task modulates the brain activity. Methods: AtDCS over the non-dominant hand area of the primary motor cortex was applied in 11 healthy subjects. Each subject participated in 2 experimental sessions (either AtDCS with an intensity of 1mA for 10 minutes or sham tDCS) in pseudo-randomized crossover design with an interval of at least 1 week. Each tDCS was applied while performing finger tapping task using non-dominant hand. Before and 10 minutes after each tDCS, BOLD signals for finger tapping task were recorded in a block design manner. Results: Brain activities in the contralateral primary sensorimotor cortex during the task were reduced after AtDCS. There was no significant change after sham tDCS. Conclusions: This finding supports that AtDCS while performing motor task decreases the motor cortex excitability as measured with transcranial magnetic stimulation (TMS). This study clarified that AtDCS in combination with the motor task induced effects different from AtDCS alone. P282 Effect of coil orientation on strength-duration time constant with controllable pulse parameter transcranial magnetic stimulation K. D’Ostilio1,2, S. Goetz3,4, M. Ciocca1,5, R. Chieffo1,6, J.-C.A. Chen1,7, A.V. Peterchev3, J.C. Rothwell1 1University College London, Sobell Department of Motor Neuroscience and Movement Disorders, London, United Kingdom; 2University of Liege, MoVeRe Group, Cyclotron Research Centre, Liège, Belgium; 3Duke University, Department of Psychiatry and Behavioral Sciences, Durham, United States; 4Technical University Munich, Munich, Germany; 5University of Milan, Department of Neurological Science, Milan, Italy; 6Scientific Institute Hospital San Raffaele, Department of Neurology, Milan, Italy; 7China Medical University Hospital, Department of Neurology, Taiwan, Taiwan Question: Controllable pulse parameter transcranial magnetic stimulation (cTMS) devices are now available. Is it possible to adjust pulse width to more selectively stimulate neuronal populations with different time constants? How does this impact on the evoked EMG responses? Methods: 10 young healthy subjects participated in the experiment (5 men/5 women). Single pulse stimulation over the hand motor area was performed using a cTMS device that generates monophasic pulses with independent control of the pulse width, connected to a figure-of-eight coil. We tested the effect of coil orientations (i.e. posterio-anterior (PA)/anteriorposterior (AP)) with three different pulse widths (30, 60 and 120 μs) on the strength-duration curve, the input-output (IO) curve and the latency of the motor evoked potentials (MEPs) in the first dorsal interosseous muscle. Results: During a weak background contraction, strength-duration time constants were estimated from both motor threshold and IO data for PA and AP orientations. When estimation was based on motor threshold data, the mean strength-duration time constants were 231 and 294 μs (t(9) =3.39; p=0.008) whereas time constants were 252 and 296 μs respectively (t(9) =8.74; p<0.001) for estimation from IO data. Repeated measure ANOVA on MEP latencies to AP and PA stimulation (during active contraction) revealed a significant interaction between pulse width and orientation (F(2,18) =9.97; p=0.001), due mainly to longer onset latencies following AP stimuli of short duration. Conclusion: The data suggests that PA and AP orientation activate neural populations with different time constants. The long time constant element activated by short duration AP pulses has a more indirect connection with the corticospinal output neurones than the PA activated population probably because it tends to recruit later I-waves. P283 Transcranial direct current stimulation (tDCS) in Parkinson’s disease R. Ferrucci1,2, M. Bianchi3, D. Pittera2, F. Cortese2, R. Turrone3, M. Vergari2, T. Bocci2, E. Tomasini2, B. Borroni3, M. Fumagalli2, F. Mameli2, E. Scelzo2, F. Cogiamanian2, G. Ardolino2, A. Di Fonzo2, A. Padovani3, A. Priori1,2 1Università degli Studi di Milano, Milan, Italy; 2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Università di Milano, Milan, Italy; 3Clinica Neurologica, Spedali Civili di Brescia, Università degli Studi di Brescia,

Development of involuntary movements after ventriculoperitoneal shunting for normal pressure hydrocephalus in a patient with chronic-phase thalamic haemorrhage

Background: Delayed-onset involuntary movements have been described after thalamic stroke. Methods: We treated a patient with involuntary movements that increased after ventriculoperitoneal shunting (VPS) for normal pressure hydrocephalus (NPH) following thalamic haemorrage. One and one-half years after right thalamic and intraventricular haemorrhage, NPH suggested clinical evaluation and neuroimaging studies in a 56-year-old man. Results: Hemidystonia and pseudochoreoathetosis were evident in the left arm, leg and trunk. Proprioceptive impairment and mild cerebellar dysfunction affected the left upper and lower extremity. Yet the patient could walk unassisted and carry out activities of daily living (ADL) rated as 90 points according to the Barthel Index (BI). Lumbar puncture lessened both gait disturbance and cognitive impairment. After VPS, cognition and urinary continence improved, but involuntary movements worsened, precluding unaided ambulation and decreasing the BI score to 65 points. Computed tomography after VPS showed resolution of NPH, while single-photon emission computed tomography showed increased cerebral blood flow after VPS. Conclusion: Increased cerebral blood flow after VPS is suspected to have promoted development of abnormal neuronal circuitry.

P31.16 The utility of diffusion tensor brain fiber tracking to evaluate diffuse axonal injury: Imaging potentially correlates with cognitive disorder

P31.16 The utility of diffusion tensor brain fiber tracking to evaluate diffuse axonal injury: Imaging potentially correlates with cognitive disorder K. Sugiyama , T. Kondo , M. Endo , H. Watanabe , K. Shindo , K. Nishijima , Y. Furusawa , T. Mori , S.I. Izumi 1 1 Tohoku University Graduate School of Medicine, Physical Medicine and Rehabilitation, Japan 2 Tohoku Kouseinenkin General Hospital, Neurology, Japan 3 Tohoku Kouseinenkin General Hospital, Physical Medicine and Rehabilitation, Japan