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Keywords: Plasticity; Recovery; Transcranial magnetic stimulation; Upper extremity. 505 Constraint-Induced Movement Therapy Results in Increased Motor Map Area in Subjects 3 to 9 Months After Stroke SAGE Publications, Inc.200810.1177/1545968308317531 LumySawaki [...]

Transcranial direct current stimulation (tDCS) can sometimes cause the opposite of its intended effect. These reverse effects may be related in part to individual differences in personality and neurochemistry. Previous studies have demonstrated that dopamine levels can impact the effects of tDCS. In the present study, 124 healthy participants took the UPPS impulsive behavior scale. Participants then underwent a single, randomized anodal or sham tDCS session on the prefrontal cortex. While the effects of tDCS were still active, they performed the Stop Signal Task, a measure of state impulsivity. tDCS was associated with increased errors on this task in people who had higher scores on the UPPS in two facets of impulsivity that correlate with dopamine levels. tDCS had no effects on people who are low in trait impulsivity. These results suggest that the reverse effects of tDCS could be associated with inter-individual differences in personality and neurochemistry. [ABSTRACT FROM AUTHOR]

MW01‐6‐189WH (MW189) is a novel central nervous system–penetrant small‐molecule drug candidate that selectively attenuates stressor‐induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first‐in‐human, randomized, double‐blind, placebo‐controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug‐related treatment‐emergent adverse event was infusion‐site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose‐proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low‐dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF‐α and higher levels of the anti‐inflammatory cytokine IL‐10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non-invasive transcranial direct current stimulation has been shown to modulate cortical excitability in various studies. Similarly, recent preliminary studies suggest that transcutaneous spinal direct current stimulation (tsDCS) may engender a modulation effect on spinal and cortical neurons. OBJECTIVE: The purpose of this study was to evaluate the dose-response effects of tsDCS in healthy subjects and thereby lay groundwork for expanding treatment options for patients with spinal cord injury (SCI). METHODS: Nine healthy subjects received each of the following 2 tsDCS conditions: Anodal and cathodal, in random order with at least 1 week washout period between each session. In order to test safety and dose response, various current intensities were used (2, 2.5 and 3 rnA) for 20 minutes. The active electrode was placed vertically over T10-T11, and the reference electrode was placed over the left shoulder. To evaluate corticospinal excitability, motor evoked potentials over soleus muscle elicited by transcranial magnetic stimulation were measured. To assess spinal cord excitability, H- and Mwave over soleus muscle to calculate Hmax/ Mmax ratio were measured. RESULTS: Linear regression showed a dose response with cathodal tsDCS on motor evoked potentials measured from the left leg as well as with anodal tsDCS on Hmax/ Mmax ratio measured from the left leg. CONCLUSIONS: These findings indicate tsDCS effects are dose-dependent. These effects should be investigated in a larger sample. [ABSTRACT FROM AUTHOR]