Human Brain Mapping
October 21, 2019
Bhim M. Adhikari, Juergen Dukart, Joerg F. Hipp et al.
24 citations
Ketamine, given at subanesthetic doses to healthy volunteers, produces psychosis-like symptoms and reduces functional connectivity in the salience network, auditory network, and default mode network (DMN). Midazolam, a sedative, only reduces DMN connectivity. The pattern of connectivity deficits caused by ketamine positively correlates with the pattern seen in schizophrenia, whereas midazolam's effects do not. After subtracting midazolam's effects, the remaining ketamine-specific disconnectivity pattern still correlates with schizophrenia deficits. This suggests that ketamine's psychosis-like effects have a brain functional basis that overlaps with schizophrenia-related connectivity disruptions.
Journal of Psychopharmacology
January 21, 2019
Rebecca McMillan, Anna Forsyth, Doug Campbell et al.
23 citations
Ketamine infusion in healthy men increases blood-oxygen-level dependent signals across the cortex and decreases them in the subgenual anterior cingulate cortex, but the decrease is largely due to physiological noise, especially cardiac pulsatility, rather than neural activity. Modeling the pharmacological MRI response with a single time course misses the full range of neural dynamics; using simultaneously recorded electroencephalography power time series reveals distinct temporal responses to ketamine, though no EEG band correlated with the subgenual anterior cingulate cortex decrease.
Human Brain Mapping
December 6, 2019
Anna Forsyth, Rebecca McMillan, Doug Campbell et al.
19 citations
The validity of fMRI functional connectivity as a drug biomarker was tested by comparing seven preprocessing pipelines and by simultaneously measuring EEG and fMRI in a placebo-controlled, three-way crossover study with ketamine and midazolam. Independent components analysis (ICA)-denoising produced stronger reductions in connectivity after ketamine and weaker increases after midazolam than pipelines using physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This indicates that pipeline decisions should match a drug's unique noise structure; when unknown, extensive ICA denoising may sacrifice some signal but increase confidence in remaining results. No significant relationship was found between changes in electrophysiological and hemodynamic correlation structures, cautioning against cross-modal comparisons of pharmacologically-modulated functional connectivity.
medRxiv : the preprint server for health sciences
October 21, 2024
Pascal Grumbach, Jan Kasper, Joerg F Hipp et al.
1 citation
preprint
Autism spectrum disorder involves altered resting-state brain function, and an imbalance between excitation and inhibition is a proposed mechanism. In two large independent cohorts, individuals with autism consistently showed reduced local brain activity in default mode network nodes and increased activity in temporal regions, cerebellum, and brainstem. These activity changes spatially overlapped with multiple neurotransmitter systems, including dopamine, glutamate, GABA, and acetylcholine. The NMDA-antagonist ketamine, but not the GABA-potentiator midazolam, induced activity changes resembling those seen in autism, suggesting that pharmacologically shifting the excitation-inhibition balance can mimic autism-related brain alterations.