Effects of Acute Ketamine Infusion on Visual Working Memory: Event-related Potentials

Article English OPEN
Koychev, I. ; William Deakin, J. F. ; El-Deredy, W. ; Haenschel, C. (2016)

Background\ud Working memory (WM) deficits are a core feature of schizophrenia. Electrophysiological studies suggest that impaired early visual processing may contribute to impaired WM in the visual domain. Abnormal N-methyl-D-aspartate (NMDA) receptor function has been implicated both in WM and in early visual processing deficits in schizophrenia. We investigated whether ketamine, a noncompetitive NMDA antagonist, would replicate in healthy volunteers the WM performance and early visual processing abnormalities we and others have reported in patients with schizophrenia.\ud \ud Methods\ud Forty-four healthy volunteers were randomly assigned to receive intravenous ketamine or placebo. During infusion, the effects of ketamine were recorded using standardized psychiatric scales. Visual evoked potentials (P100 and P300 components) were recorded during performance of a delayed matching to sample task.\ud \ud Results\ud Ketamine induced mild psychosis-like symptoms and impaired WM performance. It also significantly increased the P100 amplitude, while P300 amplitude decreased in a load-dependent manner. Amplitudes of P100 during retrieval correlated with cognitive performance only in the placebo group.\ud \ud Conclusions\ud We confirmed previous studies showing that ketamine reproduces the impairment of WM performance and smaller P300 amplitudes observed in schizophrenia. However, ketamine increased visual P100 amplitude in contrast to our observation of reduced P100 amplitudes in established schizophrenia. The effects of ketamine on WM and P300 are likely to involve impaired NMDA function, as these receptors are implicated in changes of synaptic strength underlying associative learning and memory. Increased P100 amplitude may reflect the secondary disinhibition of cortical glutamate release that occurs after NMDA blockade.
  • References (86)
    86 references, page 1 of 9

    1. Heinrichs RW (2005): The primacy of cognition in schizophrenia. Am Psychol 60:229-242.

    2. Green MF (2006): Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 67:e12.

    3. Erlenmeyer-Kimling L, Rock D, Roberts SA, Janal M, Kestenbaum C, Cornblatt B, et al. (2000): Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: The New York High-Risk Project. Am J Psychiatry 157:1416-1422.

    4. Albus M, Hubmann W, Scherer J, Dreikorn B, Hecht S, Sobizack N, et al. (2002): A prospective 2-year follow-up study of neurocognitive functioning in patients with first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci 252:262-267.

    5. Hofer A, Baumgartner S, Bodner T, Edlinger M, Hummer M, Kemmler G, et al. (2005): Patient outcomes in schizophrenia II: The impact of cognition. Eur Psychiatry 20:395-402.

    6. Milev P, Ho BC, Arndt S, Andreasen NC (2005): Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: A longitudinal first-episode study with 7-year followup. Am J Psychiatry 162:495-506.

    7. Lawlor-Savage L, Goghari VM (2014): Working memory training in schizophrenia and healthy populations. Behav Sci 4:301-319.

    8. Yeap S, Kelly SP, Sehatpour P, Magno E, Garavan H, Thakore JH, et al. (2008): Visual sensory processing deficits in schizophrenia and their relationship to disease state. Eur Arch Psychiatry Clin Neurosci 258:305-316.

    9. Butler PD, Martinez A, Foxe JJ, Kim D, Zemon V, Silipo G, et al. (2007): Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. Brain 130:417-430.

    10. Koychev I, McMullen K, Lees J, Dadhiwala R, Grayson L, Perry C, et al. (2012): A validation of cognitive biomarkers for the early identification of cognitive enhancing agents in schizotypy: A threecenter double-blind placebo-controlled study. Eur Neuropsychopharmacol 22:469-481.

  • Related Research Results (1)
  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    10
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    City Research Online - IRUS-UK 0 10
Share - Bookmark