Abstract
Numerous studies demonstrate ketamine’s influence on resting-state functional connectivity (rsFC). Seed-based and static rsFC estimation methods may oversimplify FC. These limitations can be addressed with whole-brain, dynamic rsFC estimation methods. We assessed data from 27 healthy subjects who underwent two 3 T resting-state fMRI scans, once under subanesthetic, intravenous esketamine and once under placebo, in a randomized, cross-over manner. We aimed to isolate only highly robust effects of esketamine on dynamic rsFC by using eight complementary methodologies derived from two dynamic rsFC estimation methods, two functionally defined atlases and two statistical measures. All combinations revealed a negative influence of esketamine on dynamic rsFC within the left visual network and inter-hemispherically between visual networks (p < 0.05, corrected), hereby suggesting that esketamine’s influence on dynamic rsFC is highly stable in visual processing networks. Our findings may be reflective of ketamine’s role as a model for psychosis, a disorder associated with alterations to visual processing and impaired inter-hemispheric connectivity. Ketamine is a highly effective antidepressant and studies have shown changes to sensory processing in depression. Dynamic rsFC in sensory processing networks might be a promising target for future investigations of ketamine’s antidepressant properties. Mechanistically, sensitivity of visual networks for esketamine’s effects may result from their high expression of NMDA-receptors.
Highlights
Over the last two decades, ketamine has developed significant importance in the field of psychiatry as a vehicle for the investigation of glutamatergic mechanisms in psychiatric disorders and their treatment
network based statistics (NBS) revealed that esketamine had a significant negative effect on dynamic resting-state functional connectivity (rsFC) in comparison to placebo
Any findings that were replicated with all approaches can be considered highly robust effects of esketamine administration on dynamic rsFC
Summary
Over the last two decades, ketamine has developed significant importance in the field of psychiatry as a vehicle for the investigation of glutamatergic mechanisms in psychiatric disorders and their treatment. Ketamine likely exerts circuit-specific influence[21] and seed-based assessment methods only offer snap shots of some of these effects This point can be addressed through use of whole-brain rsFC estimation methods that do not rely on seed selection. Novel approaches allowing for estimation of dynamic changes to rsFC with higher temporal resolution in humans were developed[24] Among these are the exponentially weighted sliding-window correlation method[25] and multiplication of temporal derivatives (MTD)[26]. The atlases used for rsFC estimation are often based on anatomical data and vary between studies, which creates potential for parcellation-specific effects[27,28] The influence of these methodological differences may be addressed through utilization of multiple rsFC estimation methods and atlases within one data set
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