TY  - JOUR
AU  - Forsyth, Anna
AU  - McMillan, Rebecca
AU  - Campbell, Doug
AU  - Malpas, Gemma
AU  - Maxwell, Elizabeth
AU  - Sleigh, Jamie
AU  - Dukart, Juergen
AU  - Hipp, Jörg
AU  - Muthukumaraswamy, Suresh D.
TI  - Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam
JO  - Human brain mapping
VL  - 41
IS  - 6
SN  - 1097-0193
CY  - New York, NY
PB  - Wiley-Liss
M1  - FZJ-2019-06337
SP  - 1472-1494
PY  - 2020
N1  - This work was funded by F Hoffman La Roche Ltd.
AB  - The pharmacological modulation of functional connectivity in the brain may under-lie therapeutic efficacy for several neurological and psychiatric disorders. Functionalmagnetic resonance imaging (fMRI) provides a noninvasive method of assessing thismodulation, however, the indirect nature of the blood-oxygen level dependent sig-nal restricts the discrimination of neural from physiological contributions. Here wefollowed two approaches to assess the validity of fMRI functional connectivity indeveloping drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo-controlled, three-way crossover design with ketamine andmidazolam. First, we compared seven different preprocessing pipelines to deter-mine their impact on the connectivity of common resting-state networks. Indepen-dent components analysis (ICA)-denoising resulted in stronger reductions inconnectivity after ketamine, and weaker increases after midazolam, than pipelinesemploying physiological noise modelling or averaged signals from cerebrospinalfluid or white matter. This suggests that pipeline decisions should reflect a drug'sunique noise structure, and if this is unknown then accepting possible signal losswhen choosing extensive ICA denoising pipelines could engender more confidencein the remaining results. We then compared the temporal correlation structure offMRI to that derived from two connectivity metrics of EEG, which provides a directmeasure of neural activity. While electrophysiological estimates based on thepower envelope were more closely aligned to BOLD signal connectivity than thosebased on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implyingcaution should be used when making cross-modal comparisons of pharmacologically-modulated functional connectivity.
LB  - PUB:(DE-HGF)16
C6  - pmid:31808268
UR  - <Go to ISI:>//WOS:000500765600001
DO  - DOI:10.1002/hbm.24889
UR  - https://juser.fz-juelich.de/record/867722
ER  -