Induced Suppression of the Left Dorsolateral Prefrontal Cortex Favorably Changes Interhemispheric Communication During Bimanual Coordination in Older Adults-A Neuronavigated rTMS Study

Abstract

Recent transcranial magnetic stimulation (TMS) research indicated that the ability of the dorsolateral prefrontal cortex (DLPFC) to disinhibit the contralateral primary motor cortex (M1) during motor preparation is an important predictor for bimanual motor performance in both young and older healthy adults. However, this DLPFC-M1 disinhibition is reduced in older adults. Here, we transiently suppressed left DLPFC using repetitive TMS (rTMS) during a cyclical bimanual task and investigated the effect of left DLPFC suppression: (1) on the projection from left DLPFC to the contralateral M1; and (2) on motor performance in 21 young (mean age ± SD = 21.57 ± 1.83) and 20 older (mean age ± SD = 69.05 ± 4.48) healthy adults. As predicted, without rTMS, older adults showed compromised DLPFC-M1 disinhibition as compared to younger adults and less preparatory DLPFC-M1 disinhibition was related to less accurate performance, irrespective of age. Notably, rTMS-induced DLPFC suppression restored DLPFC-M1 disinhibition in older adults and improved performance accuracy right after the local suppression in both age groups. However, the rTMS-induced gain in disinhibition was not correlated with the gain in performance. In sum, this novel rTMS approach advanced our mechanistic understanding of how left DLPFC regulates right M1 and allowed us to establish the causal role of left DLPFC in bimanual coordination.

Keywords: aging; bimanual coordination; dorsolateral prefrontal cortex; interhemispheric interaction; repetitive transcranial magnetic stimulation.

Figure 1

Experimental set-up and procedure. (A) Experimental setup. Arms were placed in palm rests for comfort. Index fingers were placed in two rotatable dials during the task. (B) Three different task conditions and their inter-hand frequency ratios. (C) Timeline of a single bimanual tracking task (BTT) trial. After 1 s, the preparatory period started by showing the blue target line. Two seconds later, an auditory “Go”-signal indicated that the participant had to start rotating the dials bimanually to follow the white target dot. Feedback of actual performance is visualized by a red tail-like line. (D) Four TMS conditions and their timing in a trial. A green stripe represents the TS on right primary motor cortex (M1). A red stripe represents the CS on the left dorsolateral prefrontal cortex (DLPFC). The blue stripes represent the rTMS train on the left DLPFC. Abbreviations: base, baseline measure at the time of target template onset; prep, measure in the preparatory period; move, measure in the movement period; TS, Test Stimulus; CS, Conditioning Stimulus; rTMS, repetitive TMS.

Figure 2

Two outcome measures for BTT performance. Tracking Error is the sum of the Euclidean distance between the subject’s cursor and the target dot (full line) plus the shortest distance between the subject’s cursor to the blue target line (dashed line), measured in arbitrary units and averaged throughout the trajectory. Movement Instability is measured as the shortest distance between the subject’s cursor and subject’s mean track (orange line), averaged throughout the trajectory.

Figure 3

Schematic overview of the experimental protocol. After a practice block, the participant had to perform two series of six blocks of ~5 min per block, wherein he/she had to execute one of the three task conditions (1:1, 1:3 and 3:1). Each block contained two TMS conditions [TS and CS-TS for interhemispheric interaction (IHI) series, and TS and rTMS-CS-TS for IHI_LESION series], delivered either at baseline (“base”) or during the preparatory period (“prep”). Also, three trials without TMS were included in each block. In the IHI_LESION series, one extra rTMS condition was included during the actual bimanual movement (“rTMS_move”).

Figure 4

Time windows used for calculation of performance outcomes during rTMS in the preparatory period (A) and the movement period (B). The duration of the early time window corresponds to the duration of the local transient lesion in the target region for rTMS. Note that for the movement period, we calculate performance ratios by dividing the performance after the pulse train by the performance before the pulse train.

Figure 5

BTT performance without (r)TMS, expressed as Tracking Error (A) and Movement Instability (B), plotted against different levels of TASK CONDITION and AGE. For both performance measures, there was a significant main effect of AGE, which was consistent over all the levels of TASK CONDITION (no significant AGE × TASK CONDITION interaction effects). Significance annotations are comparing differences between levels of TASK CONDITION, irrespective of AGE. Error bars indicate 95% CIs. Abbreviations: TE, Tracking Error; MI, Movement Instability; NS, Not Significant; ***p < 0.001.

Figure 6

IHI modulation expressed relatively to single-pulse TMS, in IHI (dots) and IHI_LESION values (triangles), for young (A) and older (B) adults. Values above 1 indicate a facilitatory effect of the CS on DLPFC to contralateral M1. Values lower than 1 indicate an inhibitory effect of the CS on DLPFC to contralateral M1. Error bars indicate 95% CIs. Abbreviations: NS, Not Significant; **p < 0.01; ***p < 0.001.

Figure 7

Tracking Error (TE) during the first 1.5 s of movement execution is plotted against IHI change scores $\left(\frac{IH{I}_{\text{prep}}}{IH{I}_{\text{base}}}\right)$, for young (dots) and older (triangles) adults. A negative correlation indicates that greater DLPFC-M1 IHI change during motor preparation is related to lower TE (i.e., better performance). The dashed line corresponds to an IHI change score of 1. Values below 1 indicate more inhibition in the late preparatory period as compared to baseline. Values above 1 indicate less inhibition (i.e., disinhibition) in the late preparatory period as compared to baseline. Abbreviations: TE, Tracking Error; Rs, Spearman’s rank correlation coefficient; **p < 0.01; ***p < 0.001.

Figure 8

Effect of DLPFC and PMd suppression on actual bimanual movement. Upper panel: left DLPFC suppression; Lower panel: right PMd suppression; Left panel: suppression during movement preparation; Right panel: suppression during movement execution. Significant differences between the condition with disruptive rTMS (black bars) and the condition without disruptive rTMS (light gray bars) are marked by frames. Error bars indicate 95% CIs. Abbreviations: TE, Tracking Error; MI, Movement Instability; rTMS, repetitive TMS; NS, Not Significant; *p < 0.05; **p < 0.01; ***p < 0.001.