Search

Question: In transcranial magnetic stimulation (TMS), two pulse waveforms are mainly used to study cortical function. While monophasic stimuli are optimal to measure cortical excitability, the biphasic pulse waveform is increasingly used to induce cortical plasticity and to treat neurological as well as psychiatric illnesses. Methods: We used a novel stimulation device (flexTMS) to study variable pulse configurations in young healthy volunteers. Primary outcome measure was cortical resting motor threshold (RMT). We determined the strength-duration relationship for single-pulse biphasic TMS using pulse durations between 120 and 400 μs. To further characterize the biphasic stimulus, we systematically varied amplitude and current direction of the first and second part of the stimulus waveform. Results: The strength-duration relation has a parabolic shape for biphasic stimulation with a minimum at a pulse length of approximately 240 μs. Varying the amplitude of the part inducing a posterior-anterior oriented current considerably raised RMT, while changes of the part which induces an anterior-posterior current had little effect. Conclusion: Our results clarify the role of pulse duration in biphasic TMS. The part inducing a posterior-anterior current in the brain contributes most to the effect of biphasic stimulation. These findings have important methodological implications and contribute to the understanding of the physiology of TMS. [Copyright &y& Elsevier]

Question: Noonan syndrome (NS; OMIM 163950) is a developmental disorder caused by activating mutations in various components of the RAS-MAPK pathway. Recent in vitro studies demonstrated impairment of synaptic plasticity caused by RAS-MAPK pathway hyperactivity. Induction of synaptic plasticity critically depends on the level of attention. We therefore studied the induction of synaptic plasticity in patients with NS and healthy volunteers under different conditions of attention using transcranial magnetic stimulation. Methods: We investigated 10 patients with NS and healthy controls (HC) using paired associative stimulation (PAS) with different attention levels (unspecific, visual and electrical attention control). Changes in motor evoked potential (MEP) amplitudes were assessed immediately after as well as 30 and 60min after PAS. Results: We demonstrated before that MEP amplitudes of healthy controls significantly increased from 1.00±0.17 to 1.74±0.50mV (p =0.001), which was not seen in patients with Noonan-Syndrome (0.88±0.09 to 1.10±0.48mV, p =0.148) and there was a significant difference between both groups (p =0.003) when using an unspecific attention control. Under specific electrical attention control, MEP amplitudes decreased significantly in patients with NS, whereas a visual attention focus diminished synaptic plasticity in healthy controls. Conclusion: Our study provides evidence that synaptic plasticity is impaired in patients with NS, which is probably a consequence of constitutive activity of the RAS-MAPK pathway. The induction of synaptic plasticity in these patients critically depends on attention and results may have direct implications for learning and memory strategies in patients with a RAS-pathway disorder. Display Omitted Display Omitted [ABSTRACT FROM AUTHOR]