Exploring working memory updating processes of the human subcortex using 7T MRI

The prefrontal-cortex basal ganglia working memory (PBWM) model (Hazy et al., 2007; O'Reilly & Frank, 2006) proposes that working memory representations are updated via a striatal gating mechanism but lacks conclusive empirical support for the postulated subcortical involvement. A growing body of research suggests that dopamine is also involved in working memory updating (Braver & Cohen, 2000; Cools & D'Esposito, 2011; D'Ardenne et al., 2012; Jongkees, 2020). In this study, we investigated subcortical -in particular, possible dopaminergic- involvement in working memory updating subprocesses using the reference-back task and ultra-high field 7 Tesla fMRI. Using a scanning protocol optimized for BOLD-sensitivity in the subcortex, we found no evidence of subcortical activation during working memory gate opening, which challenges the PBWM model's striatal gating mechanism. However, during gate closing, subcortical activation was observed. Furthermore, a ready-to-update mode demonstrated large-spread subcortical activation, including basal ganglia nuclei, suggesting that the basal ganglia are engaged in general updating processes rather than specifically controlling the working memory gate. Evidence for activity in dopaminergic midbrain regions was also observed in both contrasts. Also, substituting new information into working memory elicited activation in dopamine-producing midbrain regions along with the striatum, thalamus, and prefrontal cortex, indicating engagement of the basal ganglia-thalamo-cortical loop possibly driven by dopaminergic activity. These findings expand our understanding of subcortical regions involved in working memory updating, providing additional insights into the role of the dopaminergic midbrain.