Elsevier

Clinical Neurophysiology

Volume 116, Issue 9, September 2005, Pages 2099-2109
Clinical Neurophysiology

Normative data on changes in transcranial magnetic stimulation measures over a ten hour period

https://doi.org/10.1016/j.clinph.2005.06.006Get rights and content

Abstract

Objective

To establish normative data on the single-subject variation of resting motor thresholds and silent periods over 10 h using transcranial magnetic stimulation (TMS).

Methods

Seventeen neurologically normal volunteers aged 18–36 underwent a series of seven TMS sessions conducted over the course of a single 10-h period. During each session, resting motor threshold and cortical silent period were recorded for the first dorsal interosseus muscle of each hand during focal TMS of the contralateral motor area.

Results

We provide data on the normal limits of variability in these measures for averaged group data and for single subjects. Specifically, we report intersession, intrasession, and interhemispheric variability of data for each subject individually. Conclusions: Although group averages are highly reliable, individual subjects showed substantial variability over time, especially for silent periods. Interhemispheric asymmetry was a less stable indicator than previously reported.

Significance

These norms may guide the interpretation of changes in TMS measures within groups or within an individual patient over brief periods of time or as an immediate response to intervention.

Introduction

Transcranial magnetic stimulation (TMS) of the corticomotor pathway is increasingly used to generate diagnostic and prognostic indicators in a variety of neurological conditions. Among the most commonly used TMS measures are the amplitude and latency of the motor evoked potential (MEP) recorded in a given muscle in response to stimulation over the motor cortex, the minimal stimulation intensity required to evoke a barely perceptible MEP in a muscle at rest or during minimal voluntary contraction (motor threshold, or MT), and the duration of the period of suppression of EMG activity that follows an MEP during voluntary contraction of the target muscle (silent period, or SP).

These measures of the excitability of the corticomotor pathway are modulated by a range of internal and external influences. External influences such as subtle variations in coil positioning, electrode placement and other technical factors may contribute to some degree of measurement error. Even controlling for external influences, excitability measures retain variability attributed to internal influences such as attention, fatigue, hormonal fluctuations and other as yet undefined modulations of physiology (Civardi et al., 2001, Smith et al., 1999). Therefore, interpreting changes in TMS measures in the research or clinical context requires knowledge of normal variability.

MEP latency is quite reliable but amplitude is notoriously variable even from one trial to the next within a single subject. For this reason, we focus here on the motor threshold and silent period. The average MT and the average SP in a group of normal subjects do not change in a consistent direction on repeated testing (Manganotti et al., 2001, Strutton et al., 2003) (Fritz et al., 1997). Given the apparent reliability of these measures, MT and SP have been used to study differences between groups of subjects or within the same group of subjects before and after an experimental manipulation, such as exercise (Taylor and Gandevia, 2001) or stimulation of the central (Chen et al., 1997, Gangitano et al., 2002, Pascual-Leone et al., 1994) or peripheral (Kido Thompson, 2004, Mima et al., 2004, Uy and Ridding, 2003) nervous system.

The power to detect group differences in MT and SP is limited by the considerable intersubject variation in these measures (Orth and Rothwell, 2004). Since the measures obtained from stimulation of the two hemispheres are similar within a given individual, an alternative approach is to calculate the degree of side-to-side asymmetry in each subject. This measure is much less variable across subjects and therefore may provide a more powerful measure when comparing groups under different conditions (Kukowski and Haug, 1992, Traversa et al., 1998). This approach also has the benefit of minimizing the influence of factors that may affect excitability of the brain as a whole, such as fatigue or changes in serum concentration of anti-epileptic medications. This makes side-to-side difference a potentially more powerful measure for evaluating longitudinal changes over time in TMS measures obtained within the same group, especially for clinical groups whose disorder is lateralized to one side or hemisphere. Reports on group reliability, including asymmetry measures, however, do not indicate how much change is normal for an individual subject measured at several time points. Such normative information is essential for the clinical interpretation of changes in TMS measures in a single patient. A few reports have described intrasubject variability in MT (Wassermann, 2002) or SP (Kukowski and Haug, 1992, Fritz et al., 1997) measured with a separation of days or weeks. These studies based intrasubject variation on only two or three time points and suggest that the maximum variation of MT is 5.8% (Wassermann, 2002) and of SP duration is 10–15% (Kukowski and Haug, 1992, Orth and Rothwell, 2004).

We designed this study to generate a detailed set of data describing normal intrasubject variation in MT and in SP duration over the course of a 10-h period. Seven samples were obtained from both hemispheres over the course of the day. This provided sufficient data to calculate variability in individual subjects. This data set could be used to evaluate the clinical significance of changes in TMS measures in a single patient measured at two or more points in time. We provide data regarding group intersubject variation for comparison. To our knowledge, this is also the first study to report on interhemispheric asymmetries measured at multiple timepoints on the same day. Previous studies have addressed the issue of intersession variability using repeated measures on three or fewer time points separated by days or weeks. Other methodological differences between this and previous studies include the constancy of experimenter (the same person held the coil for all sessions) and the reliability of the scalp location, which was marked directly on the scalp at the first session and held constant throughout the experiment.

Section snippets

Subjects

This study was approved by UCLA's Medical IRB. Twenty normal volunteers were recruited from the UCLA community through advertising and word of mouth. Screening questionnaires were used to exclude volunteers with a neurological, psychiatric or serious medical history, who took medications, or in whom TMS is contraindicated (Wassermann, 1998). Subjects underwent a neurological screening examination to rule out the presence of neurological abnormality. One subject was excluded because we were

Results

Motor thresholds (MT) and silent period durations (SP) are presented in Table 1, Table 2, respectively. The motor thresholds were comparable to those obtained for the first dorsal interosseus muscle in a previous report on five normal subjects using the same stimulator (Gugino et al, 2001). The intersubject coefficient of variation in MT is 18% (last row of Table 1) and is comparable to those reported previously for the first dorsal interosseus muscle (Mills and Nithi, 1997) and for the right

Discussion

We have investigated the degree of variability in motor threshold and silent periods of the left and right hemisphere in healthy subjects measured seven times over the course of a single day. We have confirmed the relative stability of MT and SP duration in the group as a whole. The most important contribution of this work, however, is the detailed description of single-subject intersession variability and session-to-session change.

Acknowledgements

This work was supported in part by a UCLA Stein Oppenheimer Award (JMS), by RehabNet West 1 R24 HD39629-05 (LK), by NINDS 1K23NS045764-01A1 (ADW), and by General Clinical Research Centers Program M01-RR00865 (UCLA).

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    The authors have no financial interests to declare.

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