NeuroImage
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Randomized Controlled Trial
The impact of "physiological correction" on functional connectivity analysis of pharmacological resting state fMRI.
Growing interest in pharmacological resting state fMRI (RSfMRI) necessitates developing standardized and robust analytical approaches that are insensitive to spurious correlated physiological signals. However, in pharmacological experiments physiological variations constitute an important aspect of the pharmacodynamic/pharmacokinetic profile of drug action; therefore retrospective corrective methods that discard physiological signals as noise may not be suitable. Previously, we have shown that template-based dual regression analysis is a sensitive method for model-free and objective detection of drug-specific effects on functional brain connectivity. ⋯ The impact of RVHRCOR on statistical tests was limited to elimination of both morphine and alcohol effects related to the somatosensory network that consists of insula and cingulate cortex-important structures for autonomic regulation. Although our data do not warrant speculations about neuronal or vascular origins of these effects, these observations raise caution about the implications of physiological 'noise' and the risks of introducing false positives (e.g. increased white matter connectivity) by using generalized physiological correction methods in pharmacological studies. The obvious sensitivity of the posterior part of the default mode network to different correction schemes, underlines the importance of controlling for physiological fluctuations in seed-based functional connectivity analyses.