Contraction Phase and Force Differentially Change Motor Evoked Potential Recruitment Slope and Interhemispheric Inhibition in Young Versus Old

Abstract

Interhemispheric interactions are important for arm coordination and hemispheric specialization. Unilateral voluntary static contraction is known to increase bilateral corticospinal motor evoked potential (MEP) amplitude. It is unknown how increasing and decreasing contraction affect the opposite limb. Since dynamic muscle contraction is more ecologically relevant to daily activities, we studied MEP recruitment using a novel method and short interval interhemispheric inhibition (IHI) from active to resting hemisphere at 4 phases of contralateral ECR contraction: Rest, Ramp Up [increasing at 25% of maximum voluntary contraction (MVC)], Execution (tonic at 50% MVC), and Ramp Down (relaxation at 25% MVC) in 42 healthy adults. We analyzed the linear portion of resting extensor carpi radialis (ECR) MEP recruitment by stimulating at multiple intensities and comparing slopes, expressed as mV per TMS stimulation level, via linear mixed modeling. In younger participants (age ≤ 30), resting ECR MEP recruitment slopes were significantly and equally larger both at Ramp Up (slope increase = 0.047, p < 0.001) and Ramp Down (slope increase = 0.031, p < 0.001) compared to rest, despite opposite directions of force change. In contrast, Active ECR MEP recruitment slopes were larger in Ramp Down than all other phases (Rest:0.184, p < 0.001; Ramp Up:0.128, p = 0.001; Execution: p = 0.003). Older (age ≥ 60) participants' resting MEP recruitment slope was higher than younger participants across all phases. IHI did not reduce MEP recruitment slope equally in old compared to young. In conclusion, our data indicate that MEP recruitment slope in the resting limb is affected by the homologous active limb contraction force, irrespective of the direction of force change. The active arm MEP recruitment slope, in contrast, remains relatively unaffected. Older participants had steeper MEP recruitment slopes and less interhemispheric inhibition compared to younger participants.

Keywords: aging; cortical dynamics; disinhibition; interhemispheric inhibition (IHI); motor evoked potential (MEP) recruitment slope.

FIGURE 1

Motor task and experimental set-up. The participant is seated with their shoulders in approximately neutral flexion, 20° abduction, and elbows at approximately 90° flexion. The forearm and wrist are in neutral position bilaterally. The right arm is placed in a custom arm rest with soft restraints with the dorsum of the hand positioned against a force transducer connected to a six-degrees-of-freedom load cell. The visual display for each active phase is depicted. The thin vertical line is the cursor that subjects moved by applying isometric wrist extension force to the joystick. The goal is to move the cursor smoothly toward the target bar, hold within the target bar for at least 1.5 s, and make a controlled relaxation back to rest. The width and position of the target bar are scaled according to the participant’s maximum voluntary contraction (MVC).

FIGURE 2

Modeled suprathreshold MEP recruitment slope in response to 5 levels of TMS stimulus intensity (from two intervals above rMT to MAX stimulation intensity) across subjects. Comparison of suprathreshold recruitment slope in the resting L-ECR across phases of R-ECR contraction for younger and older participants in the absence and presence of IHI conditioning stimulation. Asterisks indicate significant differences between slopes for each phase from the mixed-effects spline model, planned contrast t-test *p < 0.05.

FIGURE 3

Modeled MEP recruitment slopes in the L-ECR for each phase of isometric wrist extensor contraction as a function of TS level comparing younger versus older participants in the absence (left) and presence (right) of conditioning stimulation (CS). Values were generated from a linear mixed-effects spline model with one knot at TS level 3. Asterisks indicate significant differences between younger and older groups in suprathreshold slopes from the mixed-effects model, planned contrast t-test **p < 0.01, ***p < 0.001.

FIGURE 4

Interhemispheric inhibition calculated as a percentage of conditioned MEP to unconditioned MEP for younger and older participants across task phases. (A) As a function of test stimulation (percent of resting motor threshold [rMT]). (B) At the traditional test stimulation intensity of 120% rMT. This figure illustrates the added information provided by utilizing MEP recruitment slopes gathered across multiple stimulation intensities. Values below 100% indicate inhibition and values above 100% indicate facilitation.

FIGURE 5

Comparison of suprathreshold corticospinal recruitment in the active R-ECR across phases of contraction for younger and older participants across conditioning stimulation (CS). See section “Statistical Analysis” for explanation of stimulation levels graphed on the x-axis. Asterisks indicate that Ramp Down slopes were significant different from each of the other phases from the mixed-effects liner model, planned contrast t-test **p < 0.01.

FIGURE 6

Mean root mean square of EMG background muscle activity in the resting L-ECR and active R-ECR across phases for younger and older participants. Error bars are ±1 SEM. For the R-ECR, all active phases of contraction were significantly different from each other and from rest (planned contrast t-tests, all p < 0.05, see section “Contraction Phase Rather Than Contraction Force Related to Active MEP Recruitment Amplitude”). There were no significant differences among any phases in the L-ECR [F(3,126) = 1.03, p = 0.38; see Table 6].