P 176. Evidence for high-fidelity timing dependent synaptic plasticity of human motor cortex

• Published in: Clinical neurophysiology Vol. 124; no. 10; pp. e148 - e149
• Main Authors: Cash, R., Mastaglia, F.L., Thickbroom, G.W.
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 01.10.2013
• Subjects: Neurology
• ISSN: 1388-2457; 1872-8952
• DOI: 10.1016/j.clinph.2013.04.253

A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons (known as indirect (I)-waves) which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing dependent plasticity models. Consequently we hypothesised that if the second stimulus is delivered so as not to coincide with I-wave timing it should lead to Ltd. We performed a cross-over study in ten subjects in which TMS doublets were timed to coincide (1.5ms IPI, ITMS1.5) or not coincide (2ms IPI, ITMS2) with I-wave firing. Single pulse motor evoked potential (MEP) amplitude, resting motor threshold (RMT) and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS1.5 corticomotor excitability was increased by around ∼170% for 15min (p<0.05) and returned to baseline by 20min. Increasing the IPI by just 500μs–2ms reversed the after-effect and MEP amplitude was significantly reduced (−35%, p<0.05) for 15min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS2 did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects, and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal resolution of the order of a few hundreds of microseconds.