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Ketamine Alters Lateral Prefrontal Oscillations in a Rule-Based Working Memory Task.

Liya Ma1, Kevin Skoblenick2, Kevin Johnston3

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|February 14, 2018
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Summary

Ketamine, an N-methyl-D-aspartate receptor antagonist, impairs working memory and alters neural oscillations in monkeys, mimicking schizophrenia. This study models schizophrenia

Keywords:
NMDA antagonistalpha bandbeta bandgamma bandlateral prefrontal cortexlocal field potential

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Area of Science:

  • Neuroscience
  • Cognitive Neuroscience
  • Psychiatry

Background:

  • N-methyl-D-aspartate receptor (NMDAR) antagonists induce working memory deficits akin to schizophrenia.
  • Neural oscillatory activity alterations are observed in schizophrenia but their link to NMDAR antagonism is unclear.

Purpose of the Study:

  • To investigate the effects of ketamine, an NMDAR antagonist, on neural oscillations in the lateral prefrontal cortex (LPFC) during a working memory task.
  • To determine if ketamine-induced oscillatory changes in nonhuman primates model those seen in schizophrenia.

Main Methods:

  • Recorded local field potentials (LFPs) and single-unit activity from the LPFC of rhesus macaques performing a working memory task.
  • Administered subanesthetic doses of ketamine systemically and analyzed changes in neural oscillations (alpha, beta, gamma bands).

Main Results:

  • Ketamine impaired working memory performance.
  • Ketamine enhanced low-gamma (30-60 Hz) and dampened beta (13-30 Hz) oscillations in the LPFC.
  • Ketamine reduced rule information encoded in oscillations and spike-field coherence.

Conclusions:

  • Ketamine administration in nonhuman primates provides a valid model for studying schizophrenia-related working memory deficits and altered neural synchrony.
  • Findings link NMDAR antagonism to specific oscillatory changes, offering insights into the neural network disorganization in schizophrenia.