This EEG study (n=30) in patients with depression shows that prediction error sensitivity (a possible proxy for brain plasticity, lacking in this population) is improved by ketamine (30.8mg/70kg).
“Major depressive disorder negatively impacts the sensitivity and adaptability of the brain’s predictive coding framework. The current electroencephalography study into the antidepressant properties of ketamine investigated the downstream effects of ketamine on predictive coding and short-term plasticity in thirty patients with depression using the auditory roving mismatch negativity (rMMN). The rMMN paradigm was run 3-4 h after a single 0.44 mg/kg intravenous dose of ketamine or active placebo (remifentanil infused to a target plasma concentration of 1.7 ng/mL) in order to measure the neural effects of ketamine in the period when an improvement in depressive symptoms emerges. Depression symptomatology was measured using the Montgomery-Asberg Depression Rating Scale (MADRS); 70% of patients demonstrated at least a 50% reduction their MADRS global score. Ketamine significantly increased the MMN and P3a event related potentials, directly contrasting literature demonstrating ketamine’s acute attenuation of the MMN. This effect was only reliable when all repetitions of the post-deviant tone were used. Dynamic causal modelling showed greater modulation of forward connectivity in response to a deviant tone between right primary auditory cortex and right inferior temporal cortex, which significantly correlated with antidepressant response to ketamine at 24 h. This is consistent with the hypothesis that ketamine increases sensitivity to unexpected sensory input and restores deficits in sensitivity to prediction error that are hypothesised to underlie depression. However, the lack of repetition suppression evident in the MMN evoked data compared to studies of healthy adults suggests that, at least within the short term, ketamine does not improve deficits in adaptive internal model calibration.”
Authors: Rachael L. Sumner, Rebecca McMillan, Meg J. Spriggs, Doug Campbell, Gemma Malpas, Elizabeth Maxwell, Carolyn Deng, John Hay, Rhys Ponton, Frederick Sundram & Suresh D. Muthukumaraswamy
This paper is included in our ‘Top 12 Articles on on Ketamine for Mental Health‘
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August 3, 2020
Authors associated with this publication with profiles on BlossomSuresh Muthukumaraswamy
Suresh Muthukumaraswamy (Ph.D.) is a Principal Investigator in the Centre for Brain Research and the Auckland Neuropsychopharmacology Research Group. His main research interests are in understanding how therapies alter brain activity and in developing methodologies to measure these changes in both healthy individuals and patient groups. His previous studies investigated a range of compounds including hallucinogens (ketamine, LSD, psilocybin), anesthetics, anti-epileptics, and GABA-enhancers using a wide range of neuroimaging techniques. His current work investigates ketamine and midazolam using simultaneous EEG/fMRI recordings, and the effects of ketamine, scopolamine, and rTMS in depression.
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