Mixed-effects multilevel analysis followed by canonical correlation analysis is an effective fMRI tool for the investigation of idiosyncrasies

Hum Brain Mapp. 2021 Nov;42(16):5374-5396. doi: 10.1002/hbm.25627. Epub 2021 Aug 20.


We report that regions-of-interest (ROIs) associated with idiosyncratic individual behavior can be identified from functional magnetic resonance imaging (fMRI) data using statistical approaches that explicitly model individual variability in neuronal activations, such as mixed-effects multilevel analysis (MEMA). We also show that the relationship between neuronal activation in fMRI and behavioral data can be modeled using canonical correlation analysis (CCA). A real-world dataset for the neuronal response to nicotine use was acquired using a custom-made MRI-compatible apparatus for the smoking of electronic cigarettes (e-cigarettes). Nineteen participants smoked e-cigarettes in an MRI scanner using the apparatus with two experimental conditions: e-cigarettes with nicotine (ECIG) and sham e-cigarettes without nicotine (SCIG) and subjective ratings were collected. The right insula was identified in the ECIG condition from the χ2 -test of the MEMA but not from the t-test, and the corresponding activations were significantly associated with the similarity scores (r = -.52, p = .041, confidence interval [CI] = [-0.78, -0.17]) and the urge-to-smoke scores (r = .73, p <.001, CI = [0.52, 0.88]). From the contrast between the two conditions (i.e., ECIG > SCIG), the right orbitofrontal cortex was identified from the χ2 -tests, and the corresponding neuronal activations showed a statistically meaningful association with similarity (r = -.58, p = .01, CI = [-0.84, -0.17]) and the urge to smoke (r = .34, p = .15, CI = [0.09, 0.56]). The validity of our analysis pipeline (i.e., MEMA followed by CCA) was further evaluated using the fMRI and behavioral data acquired from the working memory and gambling tasks available from the Human Connectome Project.

Keywords: Human Connectome Project; canonical correlation analysis; electronic cigarette; functional MRI; mixed-effects multilevel analysis; nicotine craving.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Craving / physiology*
  • Electronic Nicotine Delivery Systems
  • Female
  • Functional Neuroimaging*
  • Humans
  • Machine Learning
  • Magnetic Resonance Imaging
  • Male
  • Multilevel Analysis
  • Tobacco Use Disorder / diagnostic imaging
  • Tobacco Use Disorder / physiopathology*
  • Young Adult