Kei Nakagawa

Neuromagnetic beta oscillation changes during motor imagery and motor execution of skilled movements.

We showed the differences in brain activities during motor imagery and motor execution when performing single skilled movements using magnetoencephalography. The tasks included finger tapping and chopstick usage with the dominant or nondominant hand. Chopstick usage with the nondominant hand was an unfamiliar task and required higher skill. Neuromagnetic data were processed by fast Fourier transformation, and &bgr; band event-related synchronization was evaluated. Beta oscillation changes were observed in the right and left sensorimotor cortices during both tasks; however, the ipsilateral changes were smaller during motor imagery than during motor execution. These results suggest that motor imagery of skilled movement tasks causes a smaller neuronal burden in the sensorimotor cortex.

Change-related auditory P50: a MEG study.

Changes in continuous sounds elicit a preattentive component that peaks at around 100ms (Change-N1m) on electroencephalograms or magnetoencephalograms (MEG). Change-N1m is thought to reflect brain activity relating to the automatic detection of changes, which facilitate processes for the execution of appropriate behavior in response to new environmental events. The aim of the present MEG study was to elucidate whether a component relating to auditory changes existed earlier than N1m. Change-related cortical responses were evoked by abrupt sound movement in a train of clicks at 100Hz. Sound movement was created by inserting an interaural time delay (ITD) of 0.15, 0.25, 0.35, and 0.45ms into the right ear. Ten out of 12 participants exhibited clear change-related cortical responses earlier than Change-N1m at around 60ms (Change-P50m). The results of source analysis showed that Change-P50m originated from the superior temporal gyrus of both hemispheres and that its location did not differ significantly from dipoles for the response to the sound onset. The magnitude of Change-P50m increased and the peak latency shortened with an increase in the ITD, similar to those of Change-N1m. These results suggest that change-related cortical activity is present as early as its onset latency at around 50ms.

A transcranial direct current stimulation over the sensorimotor cortex modulates the itch sensation induced by histamine

OBJECTIVE Itching can be suppressed by scratching. However, scratching may aggravate itch symptoms by damaging the skin. Therefore, identifying an alternative approach to suppress itching is of clinical importance. The aim of the present study was to determine whether a transcranial direct current stimulation (tDCS) was useful for itch relief. METHODS The present study was performed on a double-blind, Sham-controlled, and cross-over experimental design. A histamine-induced itch was evoked on the left dorsal forearms of healthy participants, who were asked to report the subjective sensation of itching every 30s for 23 min. tDCS was applied over the sensorimotor cortex (SMC) according to a bi-hemispheric stimulation protocol during the itch stimuli; one electrode was placed over the right SMC, while the other was placed over the left SMC. The peak and lasting sensations of itching were compared between R-A/L-C (anodal electrode placed over the right and cathodal electrode over the left), L-A/R-C (anodal electrode placed over the left and cathodal electrode over the right), and Sham interventions. RESULTS The peak and lasting itch sensation were significantly suppressed during the R-A/L-C intervention than during the Sham intervention. On the other hand, the L-A/R-C intervention suppressed the peak itch sensation, but the effects did not last for more than a few minutes. CONCLUSIONS These results suggest that a bi-hemispheric tDCS intervention, especially when the anodal electrode was placed over the SMC of the contralateral side, was a potentially useful method for relieving lasting itch sensations. SIGNIFICANCE The present study demonstrated that a tDCS intervention may be an alternative approach for suppressing unpleasant itch sensations in healthy participants. Since tDCS has some advantages, namely, its easy application and safety in a clinical setting, it may become a useful method for the treatment of itching.

Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus

We previously demonstrated that auditory-evoked cortical responses were suppressed by a weak leading stimulus in a manner similar to the prepulse inhibition (PPI) of startle reflexes. The purpose of the present study was to investigate whether a similar phenomenon was present in the somatosensory system, and also whether this suppression reflected an inhibitory process. We recorded somatosensory-evoked magnetic fields following stimulation of the median nerve and evaluated the extent by which they were suppressed by inserting leading stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold (ST) in healthy participants (Experiment 1). The results obtained demonstrated that activity in the secondary somatosensory cortex in the hemisphere contralateral to the stimulated side (cSII) was significantly suppressed by a weak leading stimulus with the intensity larger than 1.1-fold ST. This result implied that the somatosensory system had an inhibitory process similar to that of PPI. We then presented two successive leading stimuli before the test stimulus, and compared the extent of suppression between the test stimulus-evoked responses and those obtained with the second prepulse alone and with two prepulses (first and second) (Experiment 2). When two prepulses were preceded, cSII responses to the second prepulse were suppressed by the first prepulse, whereas the ability of the second prepulse to suppress the test stimulus remained unchanged. These results suggested the presence of at least two individual pathways; response-generating and inhibitory pathways.

Transcranial direct current stimulation over the opercular somatosensory region does not influence experimentally induced pain: a triple blind, sham-controlled study.

Transcranial magnetic stimulation (TMS) over the opercular somatosensory region (OP), which includes the secondary somatosensory cortex and the insular cortex, suppresses pain sensation. However, whether transcranial direct current stimulation (tDCS) over the OP has a similar effect on pain sensation remains unknown. We examined whether pain sensation would be suppressed by tDCS over the OP. Our experiment with a triple-blind, sham-controlled, crossover design involved 12 healthy participants. Participants were asked to rate their subjective pain intensity during and after three types of bihemispheric tDCS: right anodal/left cathodal OP tDCS, left anodal/right cathodal OP tDCS (2 mA, 12 min), and sham tDCS (15 s). Pain stimuli were alternately applied to the dorsum of each index finger using intraepidermal electrical stimulation. We observed no significant effect of tDCS over the OP on the perception of experimentally induced pain. Subjective pain intensity did not differ significantly between the three tDCS conditions. The present null results have crucial implications for the selection of optimal stimulation regions and parameters for clinical pain treatment.

Inhibition in the Human Auditory Cortex.

Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI) in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms) prepulse. The time course of the inhibition evaluated by prepulses presented at 10–800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20–60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

Hypoxic Preconditioning Increases the Neuroprotective Effects of Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

The functional deficit caused by Spinal Cord Injury (SCI) is clinically incurable and current treatments have limited effects. Previous studies have suggested that cell-based therapy using Mesenchymal Stem Cells (MSCs) pre-treated with drugs or gene transfection have possible therapeutic effects. Hypoxic preconditioning is one of the most likely treatments of cell-based therapy without altering genes; however, few reports are available about Hypoxia-Preconditioned MSCs (H-MSC) transplantation for SCI. Here we demonstrate the therapeutic potential of H-MSC transplantation using SCI model rats. H-MSC expressed significantly higher mRNA levels of vascular endothelial growth factor-1 and carbonic anhydrase IX, hypoxia inducible genes. H-MSC transplantation resulted in remarkable functional improvement in the SCI model rats compared to no transplantation. Expression of brainderived neurotrophic factor and the autophagy-associated marker beclin1 mRNA was significantly upregulated in rat spinal cord that underwent H-MSC transplantation. Furthermore, conditioned medium of the H-MSC significantly prevented cell death of NG108-15 cells exposed to oxidative or inflammatory stress. These results suggest that hypoxia preconditioning is an effective strategy for SCI in cell-based therapy using MSCs.

Polarity-independent effects of transcranial direct current stimulation over the bilateral opercular somatosensory region: a magnetoencephalography study

The opercular somatosensory region (OP) plays an indispensable role in pain perception. In the present study, we investigated the neurophysiological effects of transcranial direct current stimulation (tDCS) over the OP. Somatosensory-evoked magnetic fields following noxious intraepidermal electrical stimulation to the left index finger (pain-SEFs) were recorded before and after tDCS with a single-blind, sham-controlled, cross-over trial design. Three tDCS conditions of left anodal/right cathodal tDCS, left cathodal/right anodal tDCS (each, 2 mA, 12 min), and sham tDCS (2 mA, 15 s) were applied. Despite the subjective pain sensation being unaltered, the two anodal (real) interventions significantly decreased OP activity associated with pain-SEFs. In conclusion, tDCS over the OP with the present parameters did not have a significant impact on pain sensation, but modulated its cortical processing.

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats

BACKGROUND Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury. METHODS Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed. RESULTS Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury. CONCLUSIONS The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord.

Rat Cranial Bone-Derived Mesenchymal Stem Cell Transplantation Promotes Functional Recovery in Ischemic Stroke Model Rats

The functional disorders caused by central nervous system (CNS) diseases, such as ischemic stroke, are clinically incurable and current treatments have limited effects. Previous studies suggested that cell-based therapy using mesenchymal stem cells (MSCs) exerts therapeutic effects for ischemic stroke. In addition, the characteristics of MSCs may depend on their sources. Among the derived tissues of MSCs, we have focused on cranial bones originating from the neural crest. We previously demonstrated that the neurogenic potential of human cranial bone-derived MSCs (cMSCs) was higher than that of human iliac bone-derived MSCs. Therefore, we presumed that cMSCs have a higher therapeutic potential for CNS diseases. However, the therapeutic effects of cMSCs have not yet been elucidated in detail. In the present study, we aimed to demonstrate the therapeutic effects of transplantation with rat cranial bone-derived MSCs (rcMSCs) in ischemic stroke model rats. The mRNA expression of brain-derived neurotrophic factor and nerve growth factor was significantly stronger in rcMSCs than in rat bone marrow-derived MSCs (rbMSCs). Ischemic stroke model rats in the rcMSC transplantation group showed better functional recovery than those in the no transplantation and rbMSC transplantation groups. Furthermore, in the in vitro study, the conditioned medium of rcMSCs significantly suppressed the death of neuroblastoma × glioma hybrid cells (NG108-15) exposed to oxidative and inflammatory stresses. These results suggest that cMSCs have potential as a candidate cell-based therapy for CNS diseases.