Substantia nigra activity level predicts trial-to-trial adjustments in cognitive control

Abstract

Effective adaptation to the demands of a changing environment requires flexible cognitive control. The medial and the lateral frontal cortices are involved in such control processes, putatively in close interplay with the BG. In particular, dopaminergic projections from the midbrain (i.e., from the substantia nigra [SN] and the ventral tegmental area) have been proposed to play a pivotal role in modulating the activity in these areas for cognitive control purposes. In that dopaminergic involvement has been strongly implicated in reinforcement learning, these ideas suggest functional links between reinforcement learning, where the outcome of actions shapes behavior over time, and cognitive control in a more general context, where no direct reward is involved. Here, we provide evidence from functional MRI in humans that activity in the SN predicts systematic subsequent trial-to-trial RT prolongations that are thought to reflect cognitive control in a stop-signal paradigm. In particular, variations in the activity level of the SN in one trial predicted the degree of RT prolongation on the subsequent trial, consistent with a modulating output signal from the SN being involved in enhancing cognitive control. This link between SN activity and subsequent behavioral adjustments lends support to theoretical accounts that propose dopaminergic control signals that shape behavior both in the presence and in the absence of direct reward. This SN-based modulatory mechanism is presumably mediated via a wider network that determines response speed in this task, including frontal and parietal control regions, along with the BG and the associated subthalamic nucleus.

Fig. 1

Paradigm, analysis, and data acquisition. (A) In the Stop-signal paradigm a choice-reaction stimulus (here a German traffic-light sign oriented to the left or right) is either presented during the entire trial (Go-trial, GT) or substituted by a Stop-signal (Stop-trial, ST) after a certain time delay that is set trial-to-trial by a tracking algorithm. (Additional irrelevant flanking items of random orientation were present as in Boehler et al., 2009; see Methods). This Stop-signal indicates to withhold the triggered response, yielding successful (SST) and unsuccessful Stop-trials (UST). (B) This study focuses on behavioral adaptations in Go-trials succeeding unsuccessful Stop-trials (_USTGT), successful Stop-trials (_SSTGT), or Go-trials (_GTGT). (C) Approximate slice-orientation and extent of the acquired partial volume overlaid on the MT template. (D) We specifically hypothesized that the activity level in the SN or VTA during Stop-trials would influence the RT in the subsequent Go-trial, with low activity leading to slowed subsequent responses and vice versa (the ellipsoids represent activity related to three different Stop-trials).

Fig. 2

Results of the RT-regressor analysis (mean over subjects). (A) The f/(b+1) model revealed a negative relationship between hemodynamic responses in Stop-trials and RT fluctuations in the subsequent Go-trials (_STGT) within the right SN (MNI coordinates of local activity maximum: x,y,z = 10,-22,-20). (B) Region of interest analyses revealed that this effect was only present for the RT regressors of the Go-trials following unsuccessful and successful Stop-trials (_USTGT and _SSTGT) in the f/(b+1) model.

Fig. 3

Relationship between neural activity in Stop-trials and the RT in the subsequent Go-trial in the control experiment (_STGT in the f/(b+1) model; mean over subjects). Similar to the main experiment, there was a negative relationship between hemodynamic responses in Stop-trials and RT fluctuations in the subsequent Go-trials within the right SN (MNI coordinates of local activity maximum: x,y,z = 12,-24,-14).

Fig. 4

Areas showing a significant within-trial correlation for Go-trials (f/b model; mean over subjects). A positive relationship between RTs and hemodynamic response in Go-trials, i.e. stronger activity for longer RTs, was present in the dACC/pre-SMA (A; MNI coordinates of local activity maximum: x,y,z = 2,14,50), along with several other areas and the STN (B; MNI coordinates of local activity maximum: x,y,z = 10,-16,-2).