A cerebellar thalamic cortical circuit for error-related cognitive control

Abstract

Error detection and behavioral adjustment are core components of cognitive control. Numerous studies have focused on the anterior cingulate cortex (ACC) as a critical locus of this executive function. Our previous work showed greater activation in the dorsal ACC and subcortical structures during error detection, and activation in the ventrolateral prefrontal cortex (VLPFC) during post-error slowing (PES) in a stop signal task (SST). However, the extent of error-related cortical or subcortical activation across subjects was not correlated with VLPFC activity during PES. So then, what causes VLPFC activation during PES? To address this question, we employed Granger causality mapping (GCM) and identified regions that Granger caused VLPFC activation in 54 adults performing the SST during fMRI. These brain regions, including the supplementary motor area (SMA), cerebellum, a pontine region, and medial thalamus, represent potential targets responding to errors in a way that could influence VLPFC activation. In confirmation of this hypothesis, the error-related activity of these regions correlated with VLPFC activation during PES, with the cerebellum showing the strongest association. The finding that cerebellar activation Granger causes prefrontal activity during behavioral adjustment supports a cerebellar function in cognitive control. Furthermore, multivariate GCA described the "flow of information" across these brain regions. Through connectivity with the thalamus and SMA, the cerebellum mediates error and post-error processing in accord with known anatomical projections. Taken together, these new findings highlight the role of the cerebello-thalamo-cortical pathway in an executive function that has heretofore largely been ascribed to the anterior cingulate-prefrontal cortical circuit.

Figure 1

(a) The medial frontal cortex, including the dorsal anterior cingulate cortex and supplementary motor area, as well as a cluster that includes the thalamus, epithalamus and regions in the midbrain showed greater activation during stop error (SE) as compared to go success (G) trials. BOLD contrasts were overlaid on a structural image in sagittal sections. (b) The ventrolateral prefrontal cortex showed greater activation during post-error go trials with RT slowing (pSEi) as compared to post-error go trials without RT slowing (pSEni). BOLD contrasts were overlaid on a structural image in coronal sections. Color bars represent voxel T values.

Figure 2

Brain regions (green) that Granger cause ventrolateral prefrontal cortical (VLPFC, red) activation during stop signal task. This “causality” map shows the voxel p values superimposed on a structural image in axial sections. The green scale depicts the statistical significance of the causality measure (p<0.01, uncorrected). The upper inset shows the cerebellar and pontine cluster in a sagittal view. The lower inset shows the supplementary motor area or SMA cluster (green) identified from GCA in sagittal view and its spatial relationship to the anterior cingulate cortex/SMA cluster identified from general linear modeling (blue). Please see text for further explanation.

Figure 3

Linear correlation between error-related regional activation and ventrolateral prefrontal cortical (VLPFC) activity. Each dot represents one subject. SMA: supplementary motor area; PC: left precentral cortex (PC).

Figure 4

Multivariate Granger causality analysis of the supplementary motor area (SMA), thalamus, cerebellum and ventrolateral prefrontal cortex (VLPFC). We evaluated for individual subjects whether each of the 12 connections was significant at p<0.05, corrected for false discovery rate. Group level statistics was computed using the binomial test with p<0.01. The numbers next to the arrow heads represent the number of subjects (out of 54) that show the connection. In the binomial tests, 36 (out of 54) is equivalent to p<0.00992; 37: p<0.00454; 45: p<3.64e-7; and 47: p<1.15e-8, respectively.