In our previous study, intracerebral implantation of peripheral blood stem cells (PBSCs) improved functional outcome in rats with chronic cerebral infarction. Based on this finding, a randomized, single blind controlled study was conducted in 30 patients [PBSC group (n = 15) and control group (n = 15)] with middle cerebral artery infarction confirmed on a T2-weighted MRI 6 months to 5 years after a stroke. Only subjects with neurological deficits of intermediate severity based on the National Institute of Health Stroke Scale (NIHSS; range: 9-20) that had been stable for at least 3 months were enrolled. Those in the PBSC group received subcutaneous G-CSF injections (15 μg/kg/day) for 5 consecutive days, and then stereotaxic implantation of 3-8 × 10 6 CD34 + immunosorted PBSCs. All 30 patients completed the 12-month follow-up. No serious adverse events were noted during study period. Improvements in stroke scales (NIHSS, ESS, and EMS) and functional outcomes (mRS) from baseline to the end of the 12-month follow-up period were significantly greater in the PBSC than the control group. The fiber numbers asymmetry (FNA) scores based on diffusion tensor image (DTI) tractography were reduced in every PBSC-treated subject, but not in the control group. Reduction in the FNA scores correlated well with the improvement in NIHSS. Furthermore, a positive motor-evoked potential (MEP) response by transcranial magnetic stimulation (TMS) appeared in 9 of the 15 subjects in the PBSC group. This phase II study demonstrated that implantation of autologous CD34 + PBSC was safe, feasible, and effective in improving functional outcome.
We suggest that this preliminary result is consistent with the hypothesis that, a failure in sensory attenuation contributes to the difficulties in movement initiation in Parkinson's disease.
Key pointsr We studied the interaction between the primary visual cortex and the primary motor cortex using paired transcranial magnetic stimulation (TMS) with an interstimulus interval (ISI) in the range 12-40 ms.r The connection is inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex.r The effect with an ISI of 40 ms reverses into facilitation during a visuomotor (but not audiomotor) reaction task. By contrast, there is no change in inhibition with an ISI of 18 ms, suggesting that separate pathways can be probed at different ISIs.r We conclude that a physiologically relevant occipito-motor connection can be activated by means of TMS. It may contribute to visuomotor integration, as well as being involved in certain types of visual epilepsy. AbstractThe major link between the visual and motor systems is via the dorsal stream pathways from visual to parietal and frontal areas of the cortex. Although the pathway appears to be indirect, there is evidence that visual input can reach the motor cortex at relatively short latency. To shed some light on its neural basis, we studied the visuomotor interaction using paired transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous in sixteen healthy volunteers. A conditioning stimulus (CS) was applied over the phosphene hotspot of the visual cortex, followed by a test stimulus over the left primary motor cortex (M1) with a random interstimulus interval (ISI) in range 12-40 ms. The effects of paired stimulation were retested during visual and auditory reaction-time tasks (RT). Finally, we measured the effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS over the occiput significantly (P < 0.001) suppressed test MEPs with an ISI in the range 18-40 ms. In the visual RT, inhibition with an ISI of 40 ms (but not 18 ms) was replaced by a time-specific facilitation (P < 0.001), whereas, in the auditory RT, the CS no longer had any effect on MEPs. Finally, an occipital CS facilitated SICI with an ISI of 40 ms (P < 0.01). We conclude that it is possible to study separate functional connections from visual to motor cortices using paired-TMS with an ISI in the range 18-40 ms. The connections are inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex. The effect with an ISI of 40 ms reverses into * These authors contributed equally to this work.
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