Effects of Ketamine on Frontoparietal Interactions in a Rule-Based Antisaccade Task in Macaque Monkeys.
Liya Ma, Nupur Katyare, Kevin Johnston, Stefan Everling
The Journal of neuroscience : the official journal of the Society for Neuroscience December 11, 2024 DOI: 10.1523/JNEUROSCI.1018-23.2024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 2 |
| Population | Two male macaque monkeys |
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Keywords | Cognitive control Functional connectivity Lateral prefrontal cortex Local field potentials Posterior parietal cortex Single unit Cognitive-control Brain-networks Psychopharmacology Neural-connectivity |
| Citations | 1 |
| Key findings | Ketamine reduced frontoparietal coherence and bidirectional connectivity, and compromised rule coding in prefrontal and posterior parietal neurons, with greater connectivity reductions preceding larger behavioral deficits in antisaccade performance. |
Abstract
Cognitive control is engaged by working memory processes and high-demand situations like antisaccade, where one must suppress a prepotent response. While it is known to be supported by the frontoparietal control network, how intra- and interareal dynamics contribute to cognitive control processes remains unclear. N-Methyl-d-aspartate glutamate receptors (NMDARs) play a key role in prefrontal dynamics that support cognitive control. NMDAR antagonists, such as ketamine, are known to alter task-related prefrontal activities and impair cognitive performance. However, the role of NMDAR in cognitive control-related frontoparietal dynamics remains underexplored. Here, we simultaneously recorded local field potentials and single-unit activities from the lateral prefrontal (lPFC) and posterior parietal cortices (PPC) in two male macaque monkeys during a rule-based antisaccade task, with both rule-visible (RV) and rule-memorized (RM) conditions. In addition to altering the E/I balance in both areas, ketamine had a negative impact on rule coding in true oscillatory activities. It also reduced frontoparietal coherence in a frequency- and rule-dependent manner. Granger prediction analysis revealed that ketamine induced an overall reduction in bidirectional connectivity. Among antisaccade trials, a greater reduction in lPFC-PPC connectivity during the delay period preceded a greater delay in saccadic onset under the RM condition and a greater deficit in performance under the RV condition. Lastly, ketamine compromised rule coding in lPFC neurons in both RV and RM conditions and in PPC neurons only in the RV condition. Our findings demonstrate the utility of acute NMDAR antagonists in understanding the mechanisms through which frontoparietal dynamics support cognitive control processes.
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 |