Plasticity of motor threshold and motor-evoked potential amplitude--a model of intrinsic and synaptic plasticity in human motor cortex?

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.

The time course of motor cortex plasticity after spaced motor practice.

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.

Occlusion of bidirectional plasticity by preceding low-frequency stimulation in the human motor cortex.

OBJECTIVE: Low-frequency stimulation, which does not induce long-term potentiation (LTP) or long-term potentiation (LTD) by itself, suppresses consecutive LTP or LTD induction in vitro. We tested whether a similar interaction occurs in the human motor cortex. METHODS: LTP- or LTD-like plasticity was induced using paired associative stimulation (PAS) with 25 and 10 ms interstimulus interval and conditioned by suprathreshold repetitive transcranial magnetic stimulation (rTMS) at a frequency of 0.1Hz. RESULTS: RTMS completely abolished the significant increase of motor-evoked potential (MEP) amplitudes after PAS(25 ms) (PAS(25 ms) only: 1.05+/-0.14 to 1.76+/-0.66 mV, p=0.001; rTMS+PAS(25 ms): 1.08+/-0.18 to 1.02+/-0.44 mV, n.s.) and also abolished the significant decrease of MEP amplitudes after PAS(10 ms) (PAS(10 ms) only: 1.00+/-0.14 to 0.73+/-0.32 mV; rTMS+PAS(10 ms): 1.15+/-0.35 to 1.25+/-0.43 mV, p=0.006). RTMS alone did not significantly alter MEP amplitudes but increased SICI and LICI. CONCLUSIONS: Low frequency stimulation increases intracortical inhibition and occludes LTP- and LTD-like plasticity in the human motor cortex. SIGNIFICANCE: This finding supports the concept that metaplasticity in the human motor cortex follows similar rules as metaplasticity in in vitro experiments.

Navigated transcranial magnetic stimulation does not decrease the variability of motor-evoked potentials.

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.