Differential effects of motor cortical excitability and plasticity in young and old individuals: a Transcranial Magnetic Stimulation (TMS) study

Abstract

Aging is associated with changes in the motor system that, over time, can lead to functional impairments and contribute negatively to the ability to recover after brain damage. Unfortunately, there are still many questions surrounding the physiological mechanisms underlying these impairments. We examined cortico-spinal excitability and plasticity in a young cohort (age range: 19-31) and an elderly cohort (age range: 47-73) of healthy right-handed individuals using navigated transcranial magnetic stimulation (nTMS). Subjects were evaluated with a combination of physiological [motor evoked potentials (MEPs), motor threshold (MT), intracortical inhibition (ICI), intracortical facilitation (ICF), and silent period (SP)] and behavioral [reaction time (RT), pinch force, 9 hole peg task (HPT)] measures at baseline and following one session of low-frequency (1 Hz) navigated repetitive TMS (rTMS) to the right (non-dominant) hemisphere. In the young cohort, the inhibitory effect of 1 Hz rTMS was significantly in the right hemisphere and a significant facilitatory effect was noted in the unstimulated hemisphere. Conversely, in the elderly cohort, we report only a trend toward a facilitatory effect in the unstimulated hemisphere, suggesting reduced cortical plasticity and interhemispheric communication. To this effect, we show that significant differences in hemispheric cortico-spinal excitability were present in the elderly cohort at baseline, with significantly reduced cortico-spinal excitability in the right hemisphere as compared to the left hemisphere. A correlation analysis revealed no significant relationship between cortical thickness of the selected region of interest (ROI) and MEPs in either young or old subjects prior to and following rTMS. When combined with our preliminary results, further research into this topic could lead to the development of neurophysiological markers pertinent to the diagnosis, prognosis, and treatment of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.

Keywords: aging; cortico-spinal plasticity; cortico-spinal reactivity; motor system; navigated transcranial magnetic stimulation.

Figure 1

(A) Representative first dorsal interosseus (FDI) motor evoked potentials (MEPs) data for study sample. Single pulses applied to the FDI hotspot on MR images of the subjects' brains. Left: young subject (aged 23 years); Right: older subject (aged 60 years). (B) Region of interest (ROI) selected for the correlation analysis of cortical thickness and motor evoked potentials. M: Medial; A: Anterior; P: Posterior; L: Lateral.

Figure 2

Experimental testing schematic.

Figure 3

Cortical thickness of selected region of interest (ROI) in young and old cohort.

Figure 4

Interhemispheric characteristics of the study sample prior to rTMS. Non-significant statistical differences in Motor evoked potentials (MEPs) between right and left hemispheres among young subjects (p = 0.122; Wilcoxon signed-rank test); Statistically significant differences between right and left hemispheres among older subjects (p = 0.004; Wilcoxon signed-rank test). ^*, statistically significant (p < 0.05).

Figure 5

Interhemispheric characteristics of the study sample prior to rTMS for short intracortical inhibition (SICI) and intracortical facilitation (ICF). (SICI) at interstimulus intervals of 3 ms and ICF at 12 ms (normalized and express as 100% level). Significant statistical differences in MEPs between left (p = 0.030) and right (p = 0.01) hemispheres among young subjects for ICF condition significant difference between hemispheres (p = 0.021) for young subjects; ^*, statistically significant (p < 0.05).

Figure 6

Interhemispheric characteristics for short intracortical inhibition (SICI) and intracortical facilitation (ICF). (SICI) at interstimulus intervals of 3 ms and ICF at 12 ms (normalized and express as 100% level) of the study sample after rTMS. Statistically significant increased in in MEPs for intracortical facilitation (ICF) for left hemispheres among young subjects (p = 0.002; Wilcoxon signed-rank test); ^*, statistically significant (p < 0.05).

Figure 7

Interhemispheric characteristics of the study sample after rTMS. Statistically significant differences in motor evoked potentials (MEPs) between right and left hemispheres among young subjects (p = 0.037; Wilcoxon signed-rank test); Significant differences between right and left hemispheres among older subjects (p = 0.04; Wilcoxon signed-rank test). Significant increase in MEPs in left (p = 0.01) and decrease in right (p = 0.010) hemispheres in young subjects; ^*, statistically significant (p < 0.05).

Figure 8

Interhemispheric characteristics for absolute SP measure in (ms) of the study sample prior to rTMS. significant statistical differences in absolute silent period in left hemispheres among young and old subjects (p = 0.001; Wilcoxon signed-rank test); Statistically significant differences in right hemispheres between young and older subjects (p = 0.001; Wilcoxon signed-rank test).^**, statistically significant (p < 0.05).

Figure 9

Interhemispheric characteristics measure as absolute silent period (ms) of the study sample after rTMS. Statistically significant increased in absolute silent period among young subjects (p = 0.001; Wilcoxon signed-rank test); Significant decreased in left hemispheres among older subjects (p = 0.001; Wilcoxon signed-rank test).^**, statistically significant (p < 0.05).

Figure 10

Behavioral characteristics of the study sample before rTMS for reaction time (ms) task. Statistically significant differences in reaction time between right hemispheres (p = 0.012) and left hemisphere (p = 0.01, Wilcoxon signed-rank test) among young and older subjects. ^*, statistically significant (p < 0.05).

Figure 11

Behavioral characteristics of the study sample after rTMS for reaction time (ms) task. Statistically significant increase in reaction time right hemispheres among young (p = 0.002) and older subjects (p = 0.016; Wilcoxon signed-rank test).^*, statistically significant (p < 0.05).

Figure 12

Correlations between age and MEP amplitude before and after rTMS. Top row: Correlation between age and MEP amplitude before rTMS to M1. Bottom row: Correlation between age and MEP amplitude after rTMS to M1. Correlation coefficients (r) and corresponding p-values are indicated on the figure (Spearman's rank correlation). Regression lines are shown; corresponding regression slope and intercept values are indicated on the figures.