Side-by-Side Regions in Dorsolateral Prefrontal Cortex Robustly Dissociate Salience and Working Memory

Poster Session B - Sunday, March 30, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Anne Billot^1,2, Wendy Sun^1,3, Kathryn Rodrigues^1,2, Xiangyu Wei³, Mark C. Eldaief^1,2,4,5, Randy L. Buckner^1,3,4,5; ¹Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, ²Dept. of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, ³Dept. of Psychology, Center for Brain Science, Harvard University, Cambridge, MA 02138, ⁴Dept. of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, ⁵Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129

Emphasis has traditionally been placed on the role of the dorsolateral prefrontal cortex (DLPFC) in working memory. Here we used precision functional mapping to identify two juxtaposed DLPFC regions that participate in distinct distributed networks and investigated putative behavioral dissociations between these networks. Functional networks were estimated within 14 individuals using intensive repeat sampling (Du et al., 2024). fMRI responses of adjacent DLPFC regions belonging to separate networks were repeatedly measured within each participant during N-back working memory and oddball detection tasks. We found that one DLPFC region belonging to a network coupled to the ventral striatum responded robustly to salient, transient events and could be double dissociated from an adjacent region that responded to traditional working memory demands. We further isolated these two DLPFC regions in additional controls and in patients with MDD using a single-session protocol and are now prospectively testing their response properties. These findings indicate that, at the individual level, a single fMRI acquisition session can identify side-by-side regions of DLPFC associated with distinct large-scale networks which exhibit functional double dissociations. Of interest, the DLPFC region we identified as responding to salient/transient events is the likely neuromodulatory target for the treatment of Major Depressive Disorder (MDD) in most individuals (Sun, Billot et al., 2024), further supporting its putative functional specialization.

Topic Area: EXECUTIVE PROCESSES: Working memory