A network centered on ventral premotor cortex exerts both facilitatory and inhibitory control over primary motor cortex during action reprogramming

Abstract

Ventral premotor cortex (PMv) is widely accepted to exert an important influence over primary motor cortex (M1) when hand movements are made. Although study of these interactions has typically focused on their excitatory nature, given its strong connections with both ventral and opercular frontal regions, one feature of the influence of PMv over M1 may be inhibitory. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to examine functional interactions between human PMv and M1 during the selection and reprogramming of a naturalistic goal-directed action. One of two cylinders was illuminated on each trial. It was then grasped and picked up. On some trials, however, subjects had to reprogram the action as the illuminated cylinder was switched off and the other illuminated simultaneously with reach initiation. At a neurophysiological level, the PMv paired-pulse effect (PPE) on M1 corticospinal activity was facilitatory after the initial target presentation and during movement initiation. When reprogramming was required, however, the PPE became strongly inhibitory. This context-dependent change from facilitation to inhibition occurred within 75 ms of the change of target. Behaviorally, PMv-M1 ppTMS disrupted reprogramming. Diffusion-weighted magnetic resonance image scans were taken of each subject. Intersubject differences in the facilitation-inhibition contrast of PMv-M1 interactions were correlated with fractional anisotropy of white-matter in ventral prefrontal, premotor, and intraparietal brain areas. These results suggest that a network of brain areas centered on PMv inhibits M1 corticospinal activity associated with undesired movements when action plans change.

Figures

Figure 1.

A, Behavioral task. spTMS or ppTMS was applied during most trials while subjects responded with their right hand (large cylinder stay trial shown in example). Either the large or small cylinder illuminated to initiate each trial. On stay trials the same cylinder remained illuminated throughout the trial. On switch trials, the illuminated cylinder switched from small-to-large or large-to-small when the subject's hand released the touch-bar. B, MNI coordinates for TMS targets. Circular symbols indicate individual subjects' stimulation locations in MNI152 space. Ellipsoids represent 95% confidence limits of the mean group stimulation location for each area [left M1: X= −36.5 ± 7.0 (mean ± SD), Y= −13.1 ± 6.9, Z = 64.2 ± 6.3; right PMv: X = 55.4 ± 4.0, Y = 14.7 ± 4.7, Z = 29.5 ± 4.6].

Figure 2.

PMv-M1 ppTMS facilitated M1 corticospinal activity during the premovement period and in the perimovement stay condition. However, the PPE switched to perimovement inhibition when the action had to be inhibited and reprogrammed on switch trials. A–C, Example FDI MEPs recorded after M1 spTMS and PMv-M1 ppTMS during (A) premovement, and perimovement (B) stay and (C) switch conditions. D, Group mean PPEs for each condition in the FDI muscle. E, A nonspecific facilitatory PPE was observed across all conditions when M1–M1 ppTMS was applied. Error bars represent SEM. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 3.

A–D, PMv-M1 ppTMS led to slower reprogramming on small-to-large cylinder switch trials (A), relative to the spTMS (B) or no-TMS conditions (C). This delay is quantified by the |stay − switch| GAD (D). E–H, Similar, albeit nonsignificant, trends were observed for reprogramming on large-to-small cylinder switch trials. Solid lines represent the group mean grasp aperture throughout the movement, with dashed lines representing the 95% CI of the mean. The hatched box represents the 95% CI of the mean occurrence of TMS stimulation following time normalization.

Figure 4.

A–E, White-matter FA relationships with physiological (A–C) and behavioral (D–E) effects produced by PMv-M1 ppTMS. Clusters highlighting regions that showed differential PPEs relative to the behavioral context (stay vs switch) emerged in (A) PFv at MO +75 ms, and (B) PMv and (C) IPS at MO +100 ms. Similar (D) PMv and (E) IPS clusters emerge when FA is regressed against GAD measured at 50% of MT (∼300–400 ms after the MO +100 ms time-point). Correlation clusters are indicated by red-yellow colored voxels, with green cross-hairs through the center-of-mass. Inset scatter-plots depict the FA and regressor relationships for each cluster.