A generative-predictive framework to capture altered brain activity in fMRI and its association with genetic risk: Application to Schizophrenia

Sayan Ghosal, Qiang Chen, Aaron L. Goldman, William Ulrich, Karen F. Berman, Daniel R. Weinberger, Venkata Mattay, Archana Venkataraman

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Scopus citations


We present a generative-predictive framework that captures the differences in regional brain activity between a neurotypical cohort and a clinical population, as guided by patient-specific genetic risk. Our model assumes that the functional activations in the neurotypical subjects are distributed around a population mean, and that the altered brain activity in neuropsychiatric patients is defined via deviations from this neurotypical mean. We employ group sparsity to identify a set of brain regions that simultaneously explain the salient functional differences and specify a set of basis vector, that span the low dimensional data subspace. The patient-specific projections onto this subspace are used as feature vectors to identify multivariate associations with genetic risk. We have evaluated our model on a task-based fMRI dataset from a population study of schizophrenia. We compare our model with two baseline methods, regression using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) regression, which establishes direct association between the brain activity during a working memory task and schizophrenia polygenic risk. Our model demonstrates greater consistency and robustness across bootstrapping experiments than the machine learning baselines. Moreover, the set of brain regions implicated by our model underlie the well documented executive cognitive deficits in schizophrenia.

Original languageEnglish (US)
Title of host publicationMedical Imaging 2019
Subtitle of host publicationImage Processing
EditorsElsa D. Angelini, Elsa D. Angelini, Elsa D. Angelini, Bennett A. Landman
ISBN (Electronic)9781510625457
StatePublished - 2019
EventMedical Imaging 2019: Image Processing - San Diego, United States
Duration: Feb 19 2019Feb 21 2019

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
ISSN (Print)1605-7422


ConferenceMedical Imaging 2019: Image Processing
Country/TerritoryUnited States
CitySan Diego


  • Generative-predictive Framework
  • Group Sparsity
  • Polygenetic Risk
  • Schizophrenia

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging


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