Katsunori Ikoma

Repetitive Transcranial Magnetic Stimulation of Contralesional Primary Motor Cortex Improves Hand Function After Stroke

Background and Purpose— A recent report has demonstrated that the contralesional primary motor cortex (M1) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition (TCI) in stroke patients. We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation (rTMS) caused an improved motor performance of the affected hand in stroke patients by releasing the TCI. Methods— We conducted a double-blind study of real versus sham rTMS in stroke patients. After patients had well- performed motor training to minimize the possibility of motor training during the motor measurement, they were randomly assigned to receive a subthreshold rTMS at the contralesional M1 (1 Hz, 25 minutes) or sham stimulation. Results— When compared with sham stimulation, rTMS reduced the amplitude of motor-evoked potentials in contralesional M1 and the TCI duration, and rTMS immediately induced an improvement in pinch acceleration of the affected hand, although a plateau in motor performance had been reached by the previous motor training. This improvement in motor function after rTMS was significantly correlated with a reduced TCI duration. Conclusions— We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected hand in stroke patients; this suggests a new neurorehabilitative strategy for stroke patients.

Obituary: Yukio Mano (1943–2004)

Yukio Mano, MD, PhD (1943–2004)Associate Editor, Journal of NeuroEngineering and Rehabilitation

Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial.

&NA; The double‐blinded randomized controlled trial showed that daily repetitive transcranial magnetic stimulation of primary motor cortex provided short‐term positive effect on neuropathic pain without serious adverse events. &NA; There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single‐session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double‐blind, sham‐controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5‐Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow‐up of 17 days. The primary outcome was short‐term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short‐term change in the short form of the McGill pain questionnaire (SF‐MPQ), cumulative changes in the following scores (VAS, SF‐MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty‐four NP patients were included in the intention‐to‐treat analysis. The real rTMS, compared with the sham, showed significant short‐term improvements in VAS and SF‐MPQ scores without a carry‐over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF‐MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high‐frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients.

Low-frequency repetitive TMS plus anodal transcranial DCS prevents transient decline in bimanual movement induced by contralesional inhibitory rTMS after stroke.

Background. Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected motor cortex may improve motor function of the paretic hand after stroke. However, low-frequency rTMS might adversely affect bimanual movement by decreasing transcallosal function. Objective. The authors investigated whether combined administration of rTMS and transcranial direct current stimulation (tDCS) prevents deterioration of bimanual movement induced by low-frequency rTMS over the unaffected hemisphere. Methods. A total of 27 participants with chronic subcortical stroke were randomly assigned to receive either 1 Hz rTMS over the unaffected hemisphere, anodal tDCS over the affected hemisphere, or a combination of rTMS and tDCS. All patients performed a pinching motor-training task after stimulation. Bimanual movement and transcallosal inhibition (TCI) were evaluated after stimulation. Results. rTMS and rTMS-tDCS enhanced the motor training effect on the paretic hand. rTMS decreased bimanual coordination and reduced TCI from the unaffected to the affected hemisphere (TCIunaff-aff). rTMS-tDCS changed TCI balance of both hemispheres but did not affect bimanual coordination or TCIunaff-aff. The change in bimanual coordination was negatively correlated with TCIunaff-aff. Following stimulation, improvement in the pinch force in the paretic hand was negatively correlated with TCI balance. Conclusions. Inhibitory rTMS over the unaffected hemisphere transiently caused deterioration of bimanual movements for the current task in stroke patients. This short-term decline was prevented by combined administration of low-frequency rTMS over the unaffected hemisphere and anodal tDCS over the affected hemisphere. These responses to bihemispheric stimulation suggest possible caution and opportunities for the rehabilitation of hand function after stroke.

Motor learning of hands with auditory cue in patients with Parkinson’s disease

Summary.In the present research, changes in motor cortex function were observed in relation to repetitive, voluntary thumb movement (training) in patients with Parkinson’s disease (PD) and normal control subjects. Changes in the direction of thumb movement due to motor evoked potential (MEP) by transcranial magnetic stimulation (TMS), after motor training with and without rhythmic sound, were measured using a strain gauge for 12 patients with PD and 9 normal control subjects. PD patients who experienced the freezing phenomena showed poor change in direction of TMS-induced movement after self-paced movement; however, marked change in direction of TMS-induced movement was observed after training with auditory cue. PD patients who had not experienced the freezing phenomena showed positive effects with the auditory cue, producing similar results as the normal control subjects. Two routes for voluntary movement are available in the nervous system. The decreased function of basal ganglia due to PD impaired the route from the basal ganglia to the supplementary motor cortex. These data suggest that the route from sensory input to cerebellum to premotor cortex could compensate for the decreased function of the route via the basal ganglia to the premotor cortex. Once change in the motor cortex occurred, such change persisted even after the interruption of training. These phenomena suggest that motor memory can be stored in the motor cortex.

Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage

PurposeTraumatic brain injury (TBI) causes brain dysfunction in many patients. However, some patients have severe brain dysfunction but display no abnormalities on magnetic resonance imaging (MRI). There have been some reports of hypometabolism even in such patients. The purpose of this study was to investigate the relationship between metabolic abnormality and loss of neuronal integrity in TBI patients with some symptoms but without MRI abnormalities.MethodsThe study population comprised ten patients with TBI and ten normal volunteers. All of the patients were examined at least 1 year after the injury. 15O-labelled gas PET and [11C]flumazenil (FMZ) positron emission tomography (PET) were carried out. The cerebral metabolic rate of oxygen (CMRO2) and binding potential (BP) images of FMZ were calculated. Axial T2WI, T2*WI and FLAIR images were obtained. Coronal images were added in some cases.ResultsAll of the patients had normal MRI findings, and all showed areas with abnormally low CMRO2. Low uptake on BP images was observed in six patients (60%). No lesions that showed low uptake on BP images were without low CMRO2. On the other hand, there were 14 lesions with low CMRO2 but without BP abnormalities.ConclusionThese results indicate that there are metabolic abnormalities in TBI patients with some symptoms after brain injury but without abnormalities on MRI. Some of the hypometabolic lesions showed low BP, indicating a loss of neuronal integrity. Thus, FMZ PET may have potential to distinguish hypometabolism caused by neuronal loss from that caused by other factors.

Disinhibition of the Premotor Cortex Contributes to a Maladaptive Change in the Affected Hand After Stroke

Background and Purpose— The mechanism of reorganization after stroke remains uncertain. Several studies that have measured reaction time (RT) delay by transcranial magnetic stimulation (TMS) have revealed some substrates responsible for the reorganization of motor recovery. In this study, we evaluated the RT delay and inhibitory functions by examining the silent period (SP) in the primary motor cortex (M1) and premotor cortex (PMC) of the affected hemisphere. Using these data, we investigated whether a change in the inhibitory system might influence motor recovery. Methods— This study was performed in 20 patients with chronic subcortical stroke. To evaluate the RT delay, TMS was applied to the affected hemisphere 100 ms after showing the cue that indicated paretic finger movement. The SP was induced by TMS over the affected hemisphere during voluntary contraction of the paretic hand. Results— The RT delays of the PMC were more prominent in patients with greater disability. The ratio of SP duration to RT delay in the PMC decreased with the decline in motor function. Moreover, upper arm function was better than hand function in patients with a decreased SP in the PMC. Conclusions— The inhibitory function of the PMC was disturbed in patients with poor motor function. Stroke patients with poor motor ability appeared to depend not only on the motor pathway from M1 but also on other parallel motor circuits to move the paretic side. However, this brain reorganization might result in the sacrifice of function of the affected hand.

Brain activity during the flow experience : A functional near-infrared spectroscopy study

Flow is the holistic experience felt when an individual acts with total involvement. Although flow is likely associated with many functions of the prefrontal cortex (PFC), such as attention, emotion, and reward processing, no study has directly investigated the activity of the PFC during flow. The objective of this study was to examine activity in the PFC during the flow state using functional near-infrared spectroscopy (fNIRS). Twenty right-handed university students performed a video game task under conditions designed to induce psychological states of flow and boredom. During each task and when completing the flow state scale for occupational tasks, change in oxygenated hemoglobin (oxy-Hb) concentration in frontal brain regions was measured using fNIRS. During the flow condition, oxy-Hb concentration was significantly increased in the right and left ventrolateral prefrontal cortex. Oxy-Hb concentration tended to decrease in the boredom condition. There was a significant increase in oxy-Hb concentration in the right and left dorsolateral prefrontal cortex, right and left frontal pole areas, and left ventrolateral PFC when participants were completing the flow state scale after performing the task in the flow condition. In conclusion, flow is associated with activity of the PFC, and may therefore be associated with functions such as cognition, emotion, maintenance of internal goals, and reward processing.

N200 latency and P300 amplitude in depressed mood post-traumatic brain injury patients.

In order to examine the independent and combined effects of depressive symptoms and traumatic brain injury on event-related potential (ERP) components, we classified traumatic brain injury (TBI) patients as depressed and non-depressed mood according to their scores on the Zung Self-rating Depression Scale (SDS). Non-depressed mood post-traumatic brain injury patients (NondepTBI, n = 9), depressed mood post-traumatic brain injury patients (DepTBI, n = 26), and normal healthy control subjects (HC, n = 10) were assessed for N100, N200, and P300 latencies and amplitudes by the auditory “oddball paradigm”. DepTBI subjects had significantly prolonged N200 latency and low P300 amplitude compared with the NondepTBI and HC groups. A longer P300 latency in the NondepTBI and DepTBI than in the HC groups was found. A prolongation of N200 latency accompanied by low P300 amplitude may be a characteristic of post-traumatic brain injury patients with depressed mood. Prolonged P300 latency may be more closely associated with TBI than with depression, as it was significantly greater in both the DepTBI and NondepTBI, than in the HC group.

Measurement of transcallosal inhibition in traumatic brain injury by transcranial magnetic stimulation

Primary objective: To study whether transcallosal inhibition (TCI) can evaluate the severity of traumatic brain injury (TBI). Research design: Case-control study. Methods and procedures: Twenty patients with a chronic TBI and 20 control subjects were studied. The following transcranial magnetic stimulation parameters were checked; resting motor threshold, central motor latency times, onset latency of TCI, duration of TCI, transcallosal conduction times and amount of TCI. The severity of TBI was evaluated using the Glasgow Coma Scale (GCS). Main outcome and results: The amount of TCI was significantly lower in the patients than the control subjects (p < 0.001). The amount of TCI was highly correlated with the GCS (r = 0.787, p < 0.001). Conclusion: An assessment of TCI was found to be a more sensitive and useful method for an evaluation of the severity of TBI.