Reward and loss incentives improve spatial working memory by shaping trial-by-trial posterior frontoparietal signals.

Integrating motivational signals with cognition is critical for goal-directed activities. The mechanisms that link neural changes with motivated working memory continue to be understood. Here, we tested how externally cued and non-cued (internally represented) reward and loss impact spatial working memory precision and neural circuits in human subjects using fMRI. We translated the classic delayed-response spatial working memory paradigm from non-human primate studies to take advantage of a continuous numeric measure of working memory precision, and the wealth of translational neuroscience yielded by these studies. Our results demonstrated that both cued and non-cued reward and loss improved spatial working memory precision. Visual association regions of the posterior prefrontal and parietal cortices, specifically the precentral sulcus (PCS) and intraparietal sulcus (IPS), had increased BOLD signal during incentivized spatial working memory. A subset of these regions had trial-by-trial increases in BOLD signal that were associated with better working memory precision, suggesting that these regions may be critical for linking neural signals with motivated working memory. In contrast, regions straddling executive networks, including areas in the dorsolateral prefrontal cortex, anterior parietal cortex and cerebellum displayed decreased BOLD signal during incentivized working memory. While reward and loss similarly impacted working memory processes, they dissociated during feedback when money won or avoided in loss was given based on working memory performance. During feedback, the trial-by-trial amount and valence of reward/loss received was dissociated amongst regions such as the ventral striatum, habenula and periaqueductal gray. Overall, this work suggests motivated spatial working memory is supported by complex sensory processes, and that the IPS and PCS in the posterior frontoparietal cortices may be key regions for integrating motivational signals with spatial working memory precision.

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Copyright © 2022. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declarations of Competing Interest JLJ previously worked for Neumora Therapeutics (formerly Blackthorn Therapeutics). JHK reports having received consulting payments from AstraZeneca Pharmaceuticals, Biogen, Biomedisyn Corporation, Bionomics, Boehringer Ingelheim International, COMPASS Pathways, Concert Pharmaceuticals, Epiodyne, EpiVario, Heptares Therapeutics, Janssen Research & Development, Otsuka America Pharmaceutical, Perception Neuroscience Holdings, Spring Care, Sunovion Pharmaceuticals, Takeda Industries, and Taisho Pharmaceutical. He has served on advisory boards for Bioasis Technologies, Biohaven Pharmaceuticals, BioXcel Therapeutics, Cadent Therapeutics, Cerevel Therapeutics, EpiVario, Eisai, Lohocla Research Corporation, Neumora Therapeutics, Novartis Pharmaceuticals Corporation, and PsychoGenics. He is a co-sponsor of a patent for the intranasal administration of ketamine for the treatment of depression and for the treatment of suicide risk that was licensed by Janssen Pharmaceuticals; has a patent related to the use of riluzole to treat anxiety disorders that was licensed by Biohaven Pharmaceuticals; has stock or stock options in Biohaven Pharmaceuticals, Luc Therapeutics, Cadent Pharmaceuticals, Neumora Therapeutics, Terran Biosciences, Spring Healthcare, and Sage Pharmaceuticals. He serves on the Board of Directors of Inheris Pharmaceuticals. He receives compensation for serving as editor of the journal Biological Psychiatry. GR consults for and holds equity in Neumora Therapeutics, and Manifest Sciences. JDM serves on the Technology Advisory Board for Neumora Therapeutics and holds equity, is a co-founder of Manifest Sciences and consults for Gilgamesh Pharmaceuticals. AA serves on the Technology Advisory Board for Neumora Therapeutics and holds equity, is a co-founder of Manifest Sciences and consults for Gilgamesh Pharmaceuticals. All other authors have no disclosures.