N-back task revisited: Comparing the neural correlates of updating and interference control

Working memory arises from the recruitment of multiple and multimodal specialized systems that support different executive functions, such as updating and interference control. This study revisits the n-back task, a classic working memory paradigm, directly comparing two trial types, targets and lures, to delineate the specific neural correlates of the updating and interference control within individual, and their modulation by different load conditions. This question is particularly relevant given evidence that balanced updating and interference control appear to be crucial for psychological resilience and mental health. We took an a priori approach by carefully selecting four different region-of-interest (ROI): bilateral middle frontal gyrus (MFG), inferior frontal gyrus (IFG), anterior insula, and caudate. A total of 159 healthy, right-handed young adult females (mean age = 23.33 ± 3.89 years) underwent fMRI while performing a verbal n-back task with two load levels and two stimulus types: targets and lures. Activation analyses were performed at both ROI and voxel-wise levels, and connectivity was examined through seed to voxel-wise analyses. Although updating and interference control showed an overlapping brain network, unique (and in some cases opposite) patterns arose for each process. These patterns include (i) stronger activation and differential connectivity of the MFG and caudate during targets compared with lures, (ii) increased cortical, but decreased subcortical activation with load during targets, while the opposite pattern emerged for lures, (iii) left lateralization for targets, but right lateralization during lures. This study uncovers the nuanced neural dynamics underlying updating and interference control during verbal working memory in females, underscoring the interplay between cortical and subcortical brain regions and their integration across cognitive demands.