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Effects of ketamine on frontoparietal interactions during working memory in macaque monkeys

Liya Ma, Nupur Katyare, Kevin Johnston, Stefan Everling

bioRxiv Preprint Server May 16, 2023 preprint DOI: 10.1101/2023.05.16.540957 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical experimental study
Population Macaque monkeys
Intervention Ketamine
Dose low doses
Topics Ketamine Esketamine
Keywords Neuroscience: brain function Cognitive neuroscience Neural networks Neurobiology Brain communication Working memory Brain dysconnection Brain disorders Neuropsychiatric conditions Cognitive disorders Schizophrenia Pharmacology: psychopharmacology Drug research Medication effects Neuropharmacology Translational research Monkeys Treatment development: therapeutics Drug discovery Medical research New treatments
Key findings Ketamine impairs working memory by disrupting neural coding and reducing frontoparietal connectivity and coherence in macaque monkeys.

Abstract

Schizophrenia is known as a syndrome of dysconnection among brain regions. As a model for this syndrome, low doses of N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, produce schizophrenia-like symptoms and cognitive deficits in healthy humans and animals. One of such deficits is impaired working memory, a process that engages an extended network of both frontal and parietal areas. While ketamine is known to disrupt working memory by altering both spiking and oscillatory activities in the lateral prefrontal cortex (lPFC), it remains unknown whether NMDA receptor antagonists also produce frontoparietal dysconnection during working memory processes. Here, we simultaneously recorded both single unit activities and local field potentials from lPFC and posterior parietal cortex (PPC) in macaque monkeys during a rule-based working memory task. Like previous work in the lPFC alone, we found that ketamine compromised delay-period rule coding in single neurons and reduced low-frequency oscillations in the PPC. Furthermore, ketamine reduced task-related connectivity in both fronto-parietal and parieto-frontal directions. Consistent with this, ketamine also weakened interareal coherence between spiking and low-frequency oscillatory activities. Our findings demonstrate the utility of acute NMDA receptor antagonist in simulating a syndrome of dysconnection and support this model in its potential for the exploration of novel treatment strategies for schizophrenia.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study Year Design Participants
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats 2010 Observational study
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats 1997 Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice 2016 Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats 1983 Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice 2015 Experimental study

Citations in the library

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Ketamine Esketamine