5-HT4 Receptor Agonist Effects on Functional Connectivity in the Human Brain: Implications for Procognitive Action

• DOI: 10.1016/j.bpsc.2023.03.014
• Publication Date: 2023-04-23T13:34:29Z
• Authors: Angharad N. de Cates; Marieke A.G. Martens; Lucy C. Wright; Daisy Gibson; Gershon Spitz; Cassandra D. Goul...; Sana Suri; Philip J. Cowen; Susannah E. Murphy; Catherine J. Harmer
• Keywords: Cingulate cortex; Posterior cingulate

Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal early human translational studies. Optimal cognitive performance humans is directly associated appropriate connectivity between specific resting-state neural networks. However, so far effect agonism on (rsFC) brain unknown. collected magnetic resonance imaging scans from 50 healthy volunteers, whom 25 received 6 days × 1 mg prucalopride (a highly selective agonist) placebo a randomized double-blind design. Network analyses identified participants group had enhanced rsFC central executive network posterior/anterior cingulate cortex. Seed also showed greater left right rostral anterior cortex lateral occipital cortex, reduced hippocampus other default mode regions. Similar to potentially medications, low-dose volunteers appeared enhance regions involved networks reduce within network. This suggests mechanism for behavioral enhancement previously seen supports be used clinical psychiatric populations.