Task-load-dependent activation of dopaminergic midbrain areas in the absence of reward

Abstract

Dopamine release in cortical and subcortical structures plays a central role in reward-related neural processes. Within this context, dopaminergic inputs are commonly assumed to play an activating role, facilitating behavioral and cognitive operations necessary to obtain a prospective reward. Here, we provide evidence from human fMRI that this activating role can also be mediated by task-demand-related processes and thus extends beyond situations that only entail extrinsic motivating factors. Using a visual discrimination task in which varying levels of task demands were precued, we found enhanced hemodynamic activity in the substantia nigra (SN) for high task demands in the absence of reward or similar extrinsic motivating factors. This observation thus indicates that the SN can also be activated in an endogenous fashion. In parallel to its role in reward-related processes, reward-independent activation likely serves to recruit the processing resources needed to meet enhanced task demands. Simultaneously, activity in a wide network of cortical and subcortical control regions was enhanced in response to high task demands, whereas areas of the default-mode network were deactivated more strongly. The present observations suggest that the SN represents a core node within a broader neural network that adjusts the amount of available neural and behavioral resources to changing situational opportunities and task requirements, which is often driven by extrinsic factors but can also be controlled endogenously.

Figure 1.

Paradigm and stimuli. A, Cues indicating which discrimination (high or low task demands, indicated by blue or green cue color, here represented in light gray) had to be performed were followed 1000 ms later by the brief presentation of two symbols within a peripheral rectangle in the right visual hemifield. B, Stimulus presentations either consisted of two red symbols (targets under the low task-demand condition; here represented in dark gray; left), two identical white symbols (targets under the high task-demand condition; middle), or two nonidentical white symbols (nontargets under both task instructions; right). Therefore, low-demand targets required detecting a color deviant, whereas high-demand targets required comparing the shape of two symbols. The full set of symbols is displayed (bottom; red stimuli again represented in dark gray). Note that fMRI analyses focused exclusively on nontarget trials that were physically identical under the high-demand versus low-demand conditions, thus stimulus differences cannot explain the observed fMRI results.

Figure 2.

Grand-average pupil diameter results from an independent sample of subject that was run outside of the scanner (n = 10; ±SEM; *p < 0.05). Pupil size was larger in the high-demand relative to the low-demand condition in response to cues and to targets.

Figure 3.

Comparison between nontarget trials under high versus low task demands (average of all 12 subjects; corrected cluster level p < 0.05; voxel-level threshold: t >4.5, p < 0.0005). All positive differences (red–yellow scale) reflect increased fMRI signals for high task demands relative to low task demands (comparing identical nontarget trials only), whereas all negative differences (blue–cyan scale) represent areas that were deactivated more strongly during high task demands (Tables 1, 2). pre-SMA, Pre-supplementary motor area.

Figure 4.

Activity differences in the substantia nigra (average of all 12 subjects; corrected cluster level p < 0.05; voxel-level threshold: t > 4.5, p < 0.0005). The SN displayed enhanced responses to trials with high compared with low task demands (comparing identical nontarget trials only). Activations are overlaid on the averaged spatially normalized proton-density weighted image of all participants (the SN is visible as a bright stripe of enhanced image intensity).