Towards the interpretability of deep learning models for multi-modal neuroimaging: Finding structural changes of the ageing brain
Simon M. Hofmann,
Frauke Beyer,
Sebastian Lapuschkin,
Ole Goltermann,
Markus Loeffler,
Klaus-Robert Müller,
Arno Villringer,
Wojciech Samek,
A. Veronica Witte
Affiliations
Simon M. Hofmann
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Department of Artificial Intelligence, Fraunhofer Institute Heinrich Hertz, 10587 Berlin, Germany; Clinic for Cognitive Neurology, University of Leipzig Medical Center, 04103 Leipzig, Germany; Corresponding authors at: A. Veronica Witte and Simon M. Hofmann are from Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103 Leipzig, Germany
Frauke Beyer
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic for Cognitive Neurology, University of Leipzig Medical Center, 04103 Leipzig, Germany
Sebastian Lapuschkin
Department of Artificial Intelligence, Fraunhofer Institute Heinrich Hertz, 10587 Berlin, Germany
Ole Goltermann
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Max Planck School of Cognition, 04103 Leipzig, Germany; Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Germany
Markus Loeffler
IMISE, University of Leipzig, 04103 Leipzig, Germany
Klaus-Robert Müller
Department of Electrical Engineering and Computer Science, Technical University Berlin, 10623 Berlin, Germany; Department of Artificial Intelligence, Korea University, 02841 Seoul, Korea (the Republic of); Brain Team, Google Research, 10117 Berlin, Germany; Max Planck Institute for Informatics, 66123 Saarbrücken, Germany; BIFOLD - Berlin Institute for the Foundations of Learning and Data, 10587 Berlin, Germany
Arno Villringer
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic for Cognitive Neurology, University of Leipzig Medical Center, 04103 Leipzig, Germany; MindBrainBody Institute, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10099 Berlin, Germany; Center for Stroke Research, Charité – Universitätsmedizin Berlin, 10117 Berlin, Germany
Wojciech Samek
Department of Artificial Intelligence, Fraunhofer Institute Heinrich Hertz, 10587 Berlin, Germany; Department of Electrical Engineering and Computer Science, Technical University Berlin, 10623 Berlin, Germany; BIFOLD - Berlin Institute for the Foundations of Learning and Data, 10587 Berlin, Germany
A. Veronica Witte
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic for Cognitive Neurology, University of Leipzig Medical Center, 04103 Leipzig, Germany; Corresponding authors at: A. Veronica Witte and Simon M. Hofmann are from Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103 Leipzig, Germany
Brain-age (BA) estimates based on deep learning are increasingly used as neuroimaging biomarker for brain health; however, the underlying neural features have remained unclear. We combined ensembles of convolutional neural networks with Layer-wise Relevance Propagation (LRP) to detect which brain features contribute to BA. Trained on magnetic resonance imaging (MRI) data of a population-based study (n = 2637, 18–82 years), our models estimated age accurately based on single and multiple modalities, regionally restricted and whole-brain images (mean absolute errors 3.37–3.86 years). We find that BA estimates capture ageing at both small and large-scale changes, revealing gross enlargements of ventricles and subarachnoid spaces, as well as white matter lesions, and atrophies that appear throughout the brain. Divergence from expected ageing reflected cardiovascular risk factors and accelerated ageing was more pronounced in the frontal lobe. Applying LRP, our study demonstrates how superior deep learning models detect brain-ageing in healthy and at-risk individuals throughout adulthood.