Neuroimaging-based brain-age prediction in diverse forms of epilepsy: a signature of psychosis and beyond.

Epilepsy is a diverse brain disorder, and the pathophysiology of its various forms and comorbidities is largely unknown. A recent machine learning method enables us to estimate an individual's "brain-age" from MRI; this brain-age prediction is expected as a novel individual biomarker of neuropsychiatric disorders. The aims of this study were to estimate the brain-age for various categories of epilepsy and to evaluate clinical discrimination by brain-age for (1) the effect of psychosis on temporal lobe epilepsy (TLE), (2) psychogenic nonepileptic seizures (PNESs) from MRI-negative epilepsies, and (3) progressive myoclonic epilepsy (PME) from juvenile myoclonic epilepsy (JME). In total, 1196 T1-weighted MRI scans from healthy controls (HCs) were used to build a brain-age prediction model with support vector regression. Using the model, we calculated the brain-predicted age difference (brain-PAD: predicted age-chronological age) of the HCs and 318 patients with epilepsy. We compared the brain-PAD values based on the research questions. As a result, all categories of patients except for extra-temporal lobe focal epilepsy showed a significant increase in brain-PAD. TLE with hippocampal sclerosis presented a significantly higher brain-PAD than several other categories. The mean brain-PAD in TLE with inter-ictal psychosis was 10.9 years, which was significantly higher than TLE without psychosis (5.3 years). PNES showed a comparable mean brain-PAD (10.6 years) to that of epilepsy patients. PME had a higher brain-PAD than JME (22.0 vs. 9.3 years). In conclusion, neuroimaging-based brain-age prediction can provide novel insight into or clinical usefulness for the diverse symptoms of epilepsy.