Abstract
Adaptive interpretable ensemble model based on three-dimensional Convolutional Neural Network (3DCNN) and Genetic Algorithm (GA), i.e., 3DCNN+EL+GA, was proposed to differentiate the subjects with Alzheimer's Disease (AD) or Mild Cognitive Impairment (MCI) and further identify the discriminative brain regions significantly contributing to the classifications in a data-driven way. Plus, the discriminative brain sub-regions at a voxel level were further located in these achieved brain regions, with a gradient-based attribution method designed for CNN. Besides disclosing the discriminative brain sub-regions, the testing results on the datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Open Access Series of Imaging Studies (OASIS) indicated that 3DCNN+EL+GA outperformed other state-of-the-art deep learning algorithms and that the achieved discriminative brain regions (e.g., the rostral hippocampus, caudal hippocampus, and medial amygdala) were linked to emotion, memory, language, and other essential brain functions impaired early in the AD process. Future research is needed to examine the generalizability of the proposed method and ideas to discern discriminative brain regions for other brain disorders, such as severe depression, schizophrenia, autism, and cerebrovascular diseases, using neuroimaging.