Modulation of motor cortex activity with transcranial direct current stimulation (tDCS)i patients with chronic stroke
s Neuroscience Research 68S (2010) e4 e52 e11 S1 5 2 3 Evoked activity in the cortical and subcortical motor network during transcranial magnetic stimulation to the primary motor cortex Hitoshi Shitara 1,2 Takashi Hanakawa 2,3, Tetsuya Shinozaki 1, Kenji Takagishi 1, Manabu Honda 2 1 Department of orthopaedic surgery, Gunma university graduate school of medicine, Gunma 2 Department of Functional Brain Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan 3 PRESTO, JST, Saitama, Japan Simultaneous EMG and functional MRI were conducted in 34 healthy volunteers to examine evoked activity in the cortico cortical and cortico basal ganglia network during single pulse TMS applied to the M1. Cued voluntary movement (VM) and electrical median nerve stimulation (MNS) were employed as control conditions. The motor network activity evoked by suprathreshold TMS substantially overlapped with activation during VM, and partially overlapped with activation during MNS. Peak fMRI signals were normalized with the integration of rectified EMG (iEMG) to obtain a measure of brain activity corrected for muscle afferent size. The iEMG adjusted brain activity was highest during suprathreshold TMS in both direct and remote motor areas compared with the other conditions. These results clearly show that neither local nor remote activities induced by suprathreshold TMS to M1 can be solely explained by muscle afferents. These findings clarify the quantitative relationship between TMS induced neural activation and activity signals measured by neuroimaging. doi:10.1016/j.neures.2010.07.279 S1 5 2 4 Modulation of motor cortex activity with transcranial direct current stimulation (tDCS)i patients with chronic stroke Yuko Kasashima 1 Toshiyuki Fujiwara 1, Tetsuya Tsuji 1, Junichi Ushiba 2, Meigen Liu 1 1 Department of Rehabilitation medicine, Keio University, School of Medicine 2 School of Fundamental Science and Technology, Graduate School of Keio University Transcranial direct current stumilation (tDCS) is one of the noninvasive brain stimulation methods. Anodal tDCS increases motor cortex excitability, while cathodal tDCS decreases it. Some studies showed that tDCS improves performance of motor tasks among patients with mild hemiparetic stroke. Mu ERD is interpreted as desynchronized activities of the activated neurons and appears during motor imagery. Thus it is used in brain machine interface (BMI) technology for controlling external devices such as robotic hands or motor driven orthoses. However, application of BMI to patients with severe motor disabilities is limited, because it is difficult to detect stable brain signals. If tDCS could modulate ERD, it may facilitate to detect more stable ERD for BMI application. We therefore analyzed modulation of Mu ERD induced during motor imagery with anodal and cathodal tDCS in healthy persons. Mu ERD significantly increased after anodal tDCS, while it decreased after cathodal tDCS. We also studied Mu ERD induced during motor imagery of the paretic finger movement with anodal tDCS applied to affected hemisphere in stroke patients. Mu ERD significantly increased immediately after anodal tDCS over the affected hemisphere. We then applied anodal tDCS before BMI training in patients with severe hamiparesis. BMI training combined with anodal tDCS improved motor function even in patients with severe hemiparesis. TDCS is a noninvasive tool to induce neuroplasticity and modulate cortical activities. It has enormous clinical potential for use in stroke recovery and could be one of the useful adjunct tools of rehabilitation. doi:10.1016/j.neures.2010.07.280 S1 5 2 5 Hebbian associative plasticity induced by paired bihemispheric transcranial magnetic stimulation Satoko Koganemaru 1,2 1 Department of Brain Pathophysiology, Human Brain Research Cnter, Kyoto University 2 Department of Physical and Medical Rehabilitation, Hyogo College of Medicine Paired associative stimulation (PAS) is an effective non invasive method to induce human motor plasticity by the repetitive pairing of peripheral nerve stimulation and transcranial magnetic stimulation (TMS) at the primary motor cortex (M1) with a specific time interval. Although the repetitive pairing of two types of afferent stimulation might be a biological basis of neural plasticity and memory, other types of paired stimulation of the human brain have rarely been studied. We hypothesized that the repetitive pairing of TMS and interhemispheric cortico cortical projection or paired bihemispheric stimulation (PBS) in which the right and left M1 were serially stimulated with a time interval of 15 ms, would produce an associative longterm potentiation (LTP) like effect. In this study, 23 right handed healthy volunteers were subjected to a 0.1 Hz repetition of 180 pairings of bihemispheric TMS, and physiological and behavioural measures of the motor system were compared before, immediately after, 20 min after and 40 min after PBS intervention. The amplitude of the motor evoked potential (MEP) induced by the left M1 stimulation and its input output function increased for up to ~20 min post PBS. Fine finger movements were also facilitated by PBS. Spinal excitability measured by the H reflex was insensitive to PBS, suggesting a cortical mechanism. The associative LTP like effect induced by PBS was timing dependent, occurring only when the interstimulus interval was 5 25 ms. These findings demonstrate that using PBS in PAS can induce motor cortical plasticity, and this approach might be applicable to the rehabilitation of patients with motor disorders. doi:10.1016/j.neures.2010.07.281 S1 6 1 1 Migration of cortical interneurons in living embryos Fujio Murakami Mitsutoshi Yanagida Grad Sch of Frontier Biosci, Osaka Univ, Osaka A characteristic feature of the vertebrate brain is that its neuronal cell bodies are spatially arranged, often with multiple cell types, which have distinct inputs, axonal projections. A key step to achieve this arrangement is neuronal migration. A number of studies have been carried out to uncover the mode of migration during development and underlying mechanisms by using various types of in vitro preparations. This includes explants of neural tissues, which provides in vivo like three dimensional environment for migrating neurons. However, neuronal migration in such preparations could still be different from those in vivo because of several reasons: migrating neurons are forced to stay within the extent of explant, no neuron can enter the explant from outside and axons extending through the explant are severed. Thus, observation of neuronal migration in living brain is required to find out what is genuinely happening there. We have developed a system that allows observation of neuronal migration in living embryos. Cortical interneurons were labeled by in utero electroporation of gfp into the ganglionic eminence of mouse embryos at an early embryonic stage. Embryos were removed from their dam with the umbilical cord attached a few days later, when the labeled interneurons reach the cortical marginal zone. We then performed confocal microscopy through the scull to observe labeled interneurons in the marginal zone, after removing the skin of embryos. We found that labelled interneurons vigorously migrate in the cortex. Neuronal migration could be recorded in a stable condition for more than 10 h. These neurons extended a long leading process followed by a short trailing process and showed saltatory movement. We also found that the interneurons migrated in all directions in the tangential plane. Further details of their behavior will be described in my talk. doi:10.1016/j.neures.2010.07.282 S1 6 1 2 Neural map formation in the mouse olfactory system Hitoshi Sakano Dept Biophys Biochem, Univ of Tokyo, Tokyo In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses one functional odorant receptor (OR) gene in a monoallelic manner. Furthermore, OSNs expressing a given type of OR converge their axons to a specific set of glomeruli in the olfactory bulb (OB) Recent studies demonstrated that ORs direct axon targeting along the anterior posterior (A P) axis by regulating the transcription of axon guidance molecules, e.g. Neuropilin1 and its repulsive ligand, Semapholin 3A, using OR derived cAMP signals. Pre target axon sorting within the bundle appears to be essential for the olfactory map formation along the A P axis (Imai et al. 2009) In contrast to A P projection, anatomical locations of OSNs in the olfactory epithelium (OE) are correlated with their projection sites along the dorsal ventral (D V) axis. It has been shown that OSNs in D zone extend their axons to the target earlier than those in V zone during development. Here we report that an axon guidance receptor, Neuropilin 2 (Nrp2) and its repulsive ligand, Semapholin 3F (Sema3F) play important roles in establishing the olfactory map topography along the D V axis. Genetic manipulations of Nrp2 and Sema3F result in the mistargeting of OSN axons. Furthermore, both Nrp2 and Sema3F genes
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