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Background Motor learning takes place in several phases. Animal experiments suggest that synaptic plasticity plays an important role in acquisition of motor skills, whereas retention of motor performance is most likely achieved by other mechanisms. Objective/hypothesis This study compared two spacing approaches and investigated the time course of synaptic plasticity after spaced motor practice (MP). Methods Twenty subjects performed a ballistic thumb flexion task in sessions of 6 × 10 minutes or 12 × 5 minutes. We measured peak acceleration of the target movement throughout the experiment and cortical excitability more than 60 minutes after MP via transcranial magnetic stimulation (TMS). After a retention period, both parameters were re-evaluated. Results Mean peak acceleration of the target movement significantly increased (6 × 10 minutes: 21.61 m/s 2 versus 30.80 m/s 2 , P = .002; 12 × 5 minutes: 18.52 m/s 2 versus 29.65 m/s 2 , P = .01). In both training groups, motor evoked potential (MEP) amplitudes of the trained muscle continuously increased after MP (6 × 10 min: 0.93 mV versus 1.57 mV, P = .19; 12 × 5 min: 0.90 mV versus 1.76 mV, P = .004). After the retention period, motor performance was still significantly enhanced, whereas MEP amplitudes were no longer significantly increased. Conclusions These findings do not provide evidence that in small scale motor learning the duration of practice and rest influences behavioral improvement or induction of cortical plasticity. Our study demonstrates that cortical plasticity after MP displays a dynamical time course that might be caused by different mechanisms.

Background Transcranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF). Objective/hypothesis We examined whether SICF depends on waveform and current direction of the TMS pulses. Methods In young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior–anterior (PA) or anterior–posterior (AP) current direction (AP–AP or PA–PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA–AP and AP–PA). Results Monophasic AP–AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA–PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA–AP current orientation compared with AP–PA. Conclusion SICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF.

Background Neuronal plasticity is the physiological correlate of learning and memory. In animal experiments, synaptic (i.e. long-term potentiation (LTP) and depression (LTD)) and intrinsic plasticity are distinguished. In human motor cortex, cortical plasticity can be demonstrated using transcranial magnetic stimulation (TMS). Changes in motor-evoked potential (MEP) amplitudes most likely represent synaptic plasticity and are thus termed LTP-like and LTD-like plasticity. Objective/hypothesis We investigated the role of changes of motor threshold and their relation to changes of MEP amplitudes. Methods We induced plasticity by paired associative stimulation (PAS) with 25 ms or 10 ms inter-stimulus interval or by motor practice (MP) in 64 healthy subjects aged 18–31 years (median 24.0). Results We observed changes of MEP amplitudes and motor threshold after PAS[25], PAS[10] and MP. In all three protocols, long-term individual changes in MEP amplitude were inversely correlated to changes in motor threshold (PAS[25]: P = .003, n = 36; PAS[10]: P = .038, n = 19; MP: P = .041, n = 19). Conclusion We conclude that changes of MEP amplitudes and MT represent two indices of motor cortex plasticity. Whereas increases and decreases in MEP amplitude are assumed to represent LTP-like or LTD-like synaptic plasticity of motor cortex output neurons, changes of MT may be considered as a correlate of intrinsic plasticity.

Background One major attribute of transcranial magnetic stimulation (TMS) is the variability of motor-evoked potential (MEP) amplitudes, to which variations of coil positioning may contribute. Navigated TMS allows the investigator to retrieve a stimulation site with an accuracy of 2.5 mm and to retain coil position with low spatial divergence during stimulation. Objective The purpose of this study was to investigate whether increased spatial constancy of the coil using a navigational system decreases the variability of MEP amplitudes and increases their reproducibility between different points in time of investigation. Methods We investigated eight healthy subjects (mean age 23.8 ± 1.2 years, range 22-25, four women, four men) at three different points in time with and without an optically tracked frameless navigational device, respectively. Input-output curves, motor threshold, and MEP amplitudes were recorded. We calculated the coefficient of variation as statistical parameter of variability. Reproducibility between different sessions was assessed via the MEP amplitude. Results The coefficient of variance of MEP amplitudes did not show a distinct difference between navigated and non-navigated TMS in input-output curves. MEP amplitudes, indicating reproducibility, did not significantly differ between sessions with and without navigated TMS, either. Conclusions Our results do not support the hypothesis that increased spatial constancy using a navigational system improves variability and reproducibility of MEP amplitudes. Variability of MEPs might mainly be due to not influenceable neurophysiologic factors such as undulant cortical excitability and spinal desynchronization.