Introduction 1992 1999 2002 1979 1991 2004 1995 1999 2006 2004 2003 2007 2003 2006 2003 2006 2007 1992 1999 2002 2004 2004 2005 2007 1992 2000 2005 2003 2001 2006 2003 2006 2002 The main purpose of this study was to investigate whether normal aging has an effect on the task-related modulation of IHI measured at two different latencies, 10 and 40 ms. We hypothesized that with increasing age there would be less extra activation in the inhibitory circuits targeting the M1 ipsilateral to the moving hand. In order to gain some insight of the mechanisms and the physiological meaning of these changes we also performed measures of corticospinal excitability on the side contralateral to the moving hand and looked for correlations with age and IHI measures. Methods Subjects Thirty healthy right-handed volunteers (mean age 42.9 years, range 19–78; 30% female) participated in the study after giving informed consent. They reported no history of neurological illness, psychiatric history, vascular disease or hypertension and they were not taking regular medication. The study was approved by local Ethics Committee. Transcranial magnetic stimulation Subjects were seated in an armchair with their eyes open. EMGs were recorded via Ag/AgCl electrodes placed over the First Dorsal Intersosseus (FDI) bilaterally, using a belly-tendon montage. Signals were filtered (30 Hz to 10 kHz), amplified using a Digitimer 360 (Digitimer Ltd, Welwyn Garden City, Herts., UK) and stored on computer via a Power 1401 data acquisition interface (Cambridge Electronic Design Ltd, Cambridge, UK). Analysis of data was carried out using Signal Software (Cambridge Electronic Design). Two figure-of-eight coils connected to two monophasic Magstim 200 stimulators were used for the experiments (all Magstim Co., UK). A 70-mm coil was used for motor hot spot identification and threshold measurements on both sides of the brain. The motor hotspot was defined as the scalp location where TMS consistently resulted in the largest MEP. The resting motor threshold (RMT) was defined as the lowest intensity needed to evoke an EMG response of 50 μV in 50% of the trials with the FDI relaxed; the active motor threshold (AMT) was defined as the intensity which evoked a 200 μV EMG response in 50% of the trials with a background FDI contraction of 10–15% of the maximum voluntary contraction (MVC). For all studies requiring activation of the FDI, visual feedback was provided using an oscilloscope. A recruitment curve (RC) for the active MEP amplitude elicited in the left FDI was obtained using the 70 mm coil while the subjects maintained a background FDI contraction of 15–20% MVC. Ten MEPs were collected and averaged at the following stimulus intensities: 90, 100, 110, 120, 140, 150, 160 and 170% AMT. The contraction level was tested by measuring the mean value of the rectified EMG in the 80 ms preceding the TMS pulse. The averaged peak-to-peak amplitude of the unrectified MEPs was then expressed as a ratio of the maximum peak-to-peak amplitude of the unrectified compound action potential (CMAP) evoked by supramaximal electrical stimulation of the ulnar nerve at the wrist using a Digitimer pulse stimulator (model DS7). 1992 1992 rest rest active active 2005 2007 1992 active change change Change Statistical analysis Analysis was performed using SPSS v.14 (SPSS Inc., USA). Exploratory plotting and statistical tests (Shapiro-Wilk) confirmed normal distribution for most variables. Some of the variables were skewed by a single outlier and this could not be corrected by logarithmic transformations; the outlier was therefore discarded from the dataset to allow use of parametric tests. 1 1986 1999 1997 \documentclass[12pt]{minimal}
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\begin{document}$$ {\text{MEP}} = {{\text{MEP}}_{{{\text{min}}}} + {\left( {{\text{MEP}}_{{{\text{max}}}} - {\text{MEP}}_{{{\text{min}}}} } \right)}} \mathord{\left/ {\vphantom {{{\text{MEP}}_{{{\text{min}}}} + {\left( {{\text{MEP}}_{{{\text{max}}}} - {\text{MEP}}_{{{\text{min}}}} } \right)}} {1 + \exp {\left( {{{\left( {\rm I50 - \rm I} \right)}} \mathord{\left/ {\vphantom {{{\left( {\rm I50 - \rm I} \right)}} {{\text{slope}}}}} \right. \kern-\nulldelimiterspace} {{\text{slope}}}} \right)}.}}} \right. \kern-\nulldelimiterspace} {1 + \exp {\left( {{{\left( {\rm I50 - \rm I} \right)}} \mathord{\left/ {\vphantom {{{\left( {\rm I50 - \rm I} \right)}} {{\text{slope}}}}} \right. \kern-\nulldelimiterspace} {{\text{slope}}}} \right)}.} $$\end{document} max min 1997 R 2  Fig. 1 circles line grey area  t P Results 1 Table 1 TMS measures of corticospinal excitability and interhemispheric inhibition Corticospinal excitability  Left hemisphere  Right hemisphere Motor thresholds (% stimulator’s intensity) Resting (RMT) 37.6 (28–65) 36.4 (29–50) Active (AMT) 28.4 (19–45) 28 (22–39) RC of active MEP amplitude (CMAP corrected) Mean MEP amplitude recorded  90% AMT 0.02 (0.01–0.06) –  100% AMT 0.03 (0.01–0.07)* –  110% AMT 0.06 (0.02–0.18)* –  120% AMT 0.09 (0.03–0.35)* –  140% AMT 0.25 (0.06–0.51)* –  150% AMT 0.30 (0.10–0.57)* –  160% AMT 0.34 (0.13–0.56)* –  170% AMT 0.22 (0.39–0.62) – Maximum MEP amplitude recorded 0.38 (0.13–0.62)* – AUC 12.8 (1.8–23.4)* – Parameter estimates (Boltzman model)  MEPmax/CMAP 0.4 (0.13–0.72)* –  I50 (%AMT) 137 (115–168) –  1/slope 0.14 (0.05–0.37) – IHI (targeting the right M1)  10 ms 40 ms rest 0.61 (0.32–0.9) 0.6 (0.28–1.1) active 0.54 (0.1–0.89) 0.57 (0.2–1) change active rest 0.96 (0.42–2.47) 0.97 (0.5–1.49)* max rest active change P Corticospinal excitability  r P r P r P r P r P r P r P 2 r P 2 r P Fig. 2 a b change d c rest active change  Gender was not correlated with any of the TMS measures of corticospinal excitability. Interhemispheric inhibition est t est est P 1992 2003 rest 2001 P P change change change rest change 2 change r P 2 change active resting change change r P 2004 rest r P change Discussion change rest change 1992 change change change 2006 2002 2003 2006 2007 change change 2007 2002 2004 2003 2005 B 2007 B A 2007 2004 2007 A 2001 2006 2002 2002 1998 2004 2006 2005 change change 2002 2006 2006 2006 2005 2003 a 1989 In conclusion, this study has shown for the first time that there is an age-related reduction in the extra inhibition targeting the right hemisphere during an isometric handgrip with the right hand. These changes may underlie the bihemispheric pattern of activation seen in functional imaging studies of older individuals performing a unimanual hand task. Should our findings be confirmed, studies of interhemispheric balance may prove to be a useful marker of reorganization in the aging brain.