A machine-learning approach for detection of local brain networks and marginally weak signals identifies novel AD/MCI differentiating connectomic neuroimaging biomarkers

IntroductionA computationally fast machine learning method is introduced for uncovering the wholebrain voxel-level connectomic spectra that differentiates different status of Alzheimers disease (AD). The method is applied to the Alzheimers Disease Neuroimaging Initiative (ADNI) Fluorinefluorodeoxyglucose Positron Emission Tomography (FDG-PET) imaging and clinical data and identified novel AD/MCI differentiating connectomic neuroimaging biomarkers. MethodsA divide-and-conquer algorithm is introduced for detect informative local brain networks at voxel level and whole-brain scale. The connection information within the local networks is integrated into the node voxels, which makes detection of the marginally weak signals possible. Prediction accuracy is significantly improved by incorporating the local brain networks and marginally weak signals. ResultsBrain connectomic structures differentiating AD and mild cognitive impairment (MCI), AD and healthy, and MIC and healthy were discovered. We identified novel AD/MCI-associated neuroimaging biomarkers by integrating local brain networks and marginally weak signals. For example, networkbased signals in paracentral lobule (p-value=6.1e-5), olfactory cortex (p-value=4.6e-5), caudate nucleus (1.8e-3) and precentral gyrus (1.8e-3) are informative in differentiating AD and MCI. Connections between calcarine sulcus and lingual gyrus (p-value=0.049), between parahippocampal gyrus and Amygdala (p-value=0.025), between rolandic opercula and insula lobes (p-values=0.0028 and 0.0026). An overall prediction accuracy of 95.3% was achieved by integrating the selected local brain networks and marginally weak signals, compared to 84.0% by not considering the inter-voxel connections and using marginally strong signals only. Conclusion(i) The connectomic structures differentiating AD and MCI are significantly different to that differentiating MCI and healthy, which may indicate different neuronal etiology for AD and MCI. (ii) Many neuroimaging biomarkers exert their effects on the outcome diseases through their connections to other markers. Integrating such connections can help identify novel neuroimaging biomarkers and improve disease prediction accuracy.