Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam
Anna Forsyth, Rebecca McMillan, Doug Campbell, Gemma Malpas, Elizabeth A. Maxwell, Jamie Sleigh, Juergen Dukart, Joerg F. Hipp, Suresh Muthukumaraswamy
Human Brain Mapping December 6, 2019 DOI: 10.1002/hbm.24889 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled, three-way crossover design Peer reviewed |
|---|---|
| Interventions | ketamine midazolam |
| Topics | Esketamine Ketamine |
| Keywords | Electroencephalography Communication noise Electrophysiology Resting State FMRI Neuroimaging Pattern recognition psychology Artificial intelligence |
| Citations | 19 |
| Key points | No significant relationship was found between changes in electrophysiological and hemodynamic correlation structures, implying caution should be used when making cross-modal comparisons of pharmacologically-modulated functional connectivity. |
Abstract
The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood-oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo-controlled, three-way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting-state networks. Independent components analysis (ICA)-denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross-modal comparisons of pharmacologically-modulated functional connectivity.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 7
- Human brain effects of DMT assessed via EEG-fMRI. Proceedings of the National Academy of Sciences March 28, 2023
- Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anesthetized states induced by ketamine Neuroimage January 7, 2022
- Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine. Translational Psychiatry February 24, 2024
- Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study Brain Structure and Function August 7, 2021
- Local activity alterations in autism spectrum disorder correlate with neurotransmitter properties and ketamine induced brain changes. medRxiv October 21, 2024
and 2 more in the library
Cites 13
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Frontal theta EEG activity correlates negatively with the default mode network in resting state International Journal of Psychophysiology July 13, 2007
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
and 8 more in the library