Optimization of the Transcranial Magnetic Stimulation Protocol by Defining a Reliable Estimate for Corticospinal Excitability

<div><p>The goal of this study was to optimize the transcranial magnetic stimulation (TMS) protocol for acquiring a reliable estimate of corticospinal excitability (CSE) using single-pulse TMS. Moreover, the minimal number of stimuli required to obtain a reliable estimate of CSE was investigated. In addition, the effect of two frequently used stimulation intensities [110% relative to the resting motor threshold (rMT) and 120% rMT] and gender was evaluated. Thirty-six healthy young subjects (18 males and 18 females) participated in a double-blind crossover procedure. They received 2 blocks of 40 consecutive TMS stimuli at either 110% rMT or 120% rMT in a randomized order. Based upon our data, we advise that at least 30 consecutive stimuli are required to obtain the most reliable estimate for CSE. Stimulation intensity and gender had no significant influence on CSE estimation. In addition, our results revealed that for subjects with a higher rMT, fewer consecutive stimuli were required to reach a stable estimate of CSE. The current findings can be used to optimize the design of similar TMS experiments.</p></div

The number of TMS stimuli required to reach a probability of 1.0 for hitting the 95% CI was estimated using the GEE analysis for different levels of resting motor threshold (rMT).

<p>The number of TMS stimuli required to reach a probability of 1.0 for hitting the 95% CI was estimated using the GEE analysis for different levels of resting motor threshold (rMT).</p

Probability table.

<p>The number of consecutive stimuli required as a function of the probability of hitting the 95% confidence interval (CI).</p

Visual Analogue Scales (VAS).

<p>The mean VAS score ± standard deviation (SD) is shown for attention (0 = no attention; 10 = maximal attention), fatigue (0 = no fatigue; 10 = maximal fatigue) and arousal (0 = no arousal; 10 = maximal arousal). Measurements were obtained prior (PRE) and after (POST) the experiment. Data is shown for all subjects and for males and females separately. P-values in bold highlight a significant effect between PRE and POST measurement.</p

Data for subject 36 (a) and 34 (b) is illustrated.

<p>The Y-axis shows the MEP amplitude (mV), while the number of TMS stimuli (n) is shown on the X-axis. White dots represent the individual (raw) MEPs, whereas the black dots represent the average of consecutive MEPs (). Dashed lines represent the 95% confidence interval (CI), which is based upon all 40 stimuli. The upper panel (<b>a</b>) illustrates data that was included in the statistical analysis (slope estimate: 0.007; p = 0.355). For this particular subject, 8 consecutive stimuli were sufficient to enter the CI. The lower panel (<b>b</b>) shows data that has been excluded due to a significant change in slope over time (slope estimate: 0.062; p<0.001).</p

Results for gender (a) and intensity (b) based upon the raw data are illustrated.

<p>The Y-axis shows probability of inclusion in the 95% CI, while the number of TMS stimuli (n) is shown on the X-axis. The upper panel (<b>a</b>) illustrates the probability of inclusion in the 95% CI for females (white dots) and males rMT (black dots). The lower panel (<b>b</b>) illustrates the probability of inclusion in the 95% CI for the stimulation intensity of 110% rMT (white dots) and 120% rMT (black dots).</p

Generalized estimating equation (GEE) analysis.

<p>Estimates and p-values are shown for the number of consecutive stimuli, arousal, fatigue, resting motor threshold and the interaction between arousal and fatigue. P-values in bold highlight a significant effect.</p

Improvement from Pre-test to Retention.

<p>Improvement (in percentage), i.e., inverse of error decrease, of Retention compared to Pre-test under feedback per group for AE (left) and SD (right). Filled dots & striped lines: improvements on relative phase (RPH); Open dots & solid lines: improvements on relative cycling frequency ratio (CFR).</p

Results of the 3×5×2 ANOVAs (<i>F</i>-values) for absolute error (AE) and variability scores of relative phase (SDΦ) and cycling frequency ratio (CFR).

<p>* <i>p</i><0.05,</p>**<p><i>p</i><0.01,</p>***<p>, <i>p</i><0.001.</p>†<p>Marginally significant (<i>p</i><0.1).</p

Experimental setup.

<p>A. Apparatus consisting of torque motors, forearm rests, moving hand pieces, and a pc providing feedback. B. Positioning of participants during task execution. C. Lissajous plot of the goal (1∶2 frequency ratio with a 90° phase offset between limbs) produced by both limb displacements.</p