Age-Related Weakness of Proximal Muscle Studied with Motor Cortical Mapping: A TMS Study

Abstract

Aging-related weakness is due in part to degeneration within the central nervous system. However, it is unknown how changes to the representation of corticospinal output in the primary motor cortex (M1) relate to such weakness. Transcranial magnetic stimulation (TMS) is a noninvasive method of cortical stimulation that can map representation of corticospinal output devoted to a muscle. Using TMS, we examined age-related alterations in maps devoted to biceps brachii muscle to determine whether they predicted its age-induced weakness. Forty-seven right-handed subjects participated: 20 young (22.6±0.90 years) and 27 old (74.96±1.35 years). We measured strength as force of elbow flexion and electromyographic activation of biceps brachii during maximum voluntary contraction. Mapping variables included: 1) center of gravity or weighted mean location of corticospinal output, 2) size of map, 3) volume or excitation of corticospinal output, and 4) response density or corticospinal excitation per unit area. Center of gravity was more anterior in old than in young (p<0.001), though there was no significant difference in strength between the age groups. Map size, volume, and response density showed no significant difference between groups. Regardless of age, center of gravity significantly predicted strength (β = −0.34, p = 0.005), while volume adjacent to the core of map predicted voluntary activation of biceps (β = 0.32, p = 0.008). Overall, the anterior shift of the map in older adults may reflect an adaptive change that allowed for the maintenance of strength. Laterally located center of gravity and higher excitation in the region adjacent to the core in weaker individuals could reflect compensatory recruitment of synergistic muscles. Thus, our study substantiates the role of M1 in adapting to aging-related weakness and subtending strength and muscle activation across age groups. Mapping from M1 may offer foundation for an examination of mechanisms that preserve strength in elderly.

Reproducibility of transcranial magnetic stimulation metrics in the study of proximal upper limb muscles

“…Biceps brachii, being a proximal large muscle, is especially important in founding subsequent recovery of the hand in neurologic populations (Kumar et al, 1989). However, based on present findings and previous evidence from our work and of others (Plow et al, 2013; Plow et al, 2014; van Kuijk et al, 2009; Brasil-Neto et al, 1992), it becomes clear that the variable nature of its MEPs renders test-retest measurements of its TMS metrics weakly reproducible. Nevertheless, choosing metrics that define its excitability and output in terms of intensity of TMS device (RMTs or supra-maximal MEP intensities) and/or spatial spread of excitability (COGs and hotspots) would serve as robust markers to longitudinally track recovery and prognosticate upper extremity function across populations, such as stroke, and spinal cord injury.…”

“…Our emphasis is novel because proximal muscles are typically less studied than distal owing to the challenge in assaying with TMS. For instance, fewer cortico-motor-neuronal projections that are spread over a relatively wider area (Brasil-Neto et al, 1992), we have recently reported, render their MEPs small and extremely variable (Plow et al, 2013, 2014). Along similar lines, examining reliability of all major metrics is important, because in the study of distal muscles, a divergence is identified, where certain measures are more reliable than others (Malcolm et al, 2006).…”

“…Within each session, single-pulse and paired-pulse TMS were applied to the right hemisphere for studying metrics for left biceps brachii. We chose to investigate metrics for the non-dominant, left biceps brachii, because this study was part of a larger study evaluating the weaker left arm in healthy young versus an aged population (Plow et al, 2014), where the differences in corticospinal excitation between young and old were most accentuated on the left side in right-handed participants.…”

“…MEPs within the range of 0.1-0.4 mV were categorized as ‘MEPs with lower amplitude’ whereas those within 0.4-0.7 mV were categorized as ‘MEPs with higher amplitude’. The criterion ranges of supra-maximal MEPs were set lower than that which is generally adopted for study of distal hand muscles (~1 mV) because it is difficult to evoke larger MEPs from biceps brachii (Chen et al, 1998; Harris-Love et al, 2007; Plow et al, 2014). A wider range was chosen because MEPs elicited in biceps brachii are more variable (Brasil-Neto et al, 1992; Plow et al, 2013,) than those in distal muscles (van Kuijk et al, 2009).…”

“…Our mapping procedure involves a higher-than-typical spatial resolution (3 vs 10 mm) because Brasil-Neto and colleagues have recommended that weaker cortical representations of proximal muscles can be accurately studied only at high spatial resolution than that used for study of distal (Brasil-Neto et al, 1992). Sites were deemed responsive if they produced peak-to-peak MEPs of at least 10 μV, over two trials as discussed in our recent work (Plow et al, 2014) and as used by others (Streletz et al, 1995; Marconi et al, 2011). The reason the criterion for motor mapping (MEPs of at least 10 μV) was set at a lower amplitude than that which is typically used for RMT was that in a proximal muscle, such as biceps brachii, it is difficult to obtain MEPs of higher amplitude (Chen et al 1998 and Harris-Love et al 2007) unlike in a distal muscle (Rossini et al 1994 and Mills et al 1997).…”