Multimodal connectome biomarkers of cognitive and affective dysfunction in the common epilepsies

Epilepsy is one of the most common chronic neurological conditions, traditionally defined as a disorder of recurrent seizures. Cognitive and affective dysfunction are increasingly recognized as core disease dimensions and can affect patient well-being, sometimes more than the seizures themselves. Connectome-based approaches hold immense promise for revealing mechanisms that contribute to dysfunction and to identify biomarkers. Our review discusses emerging multimodal neuroimaging and connectomics studies that highlight network substrates of cognitive/affective dysfunction in the common epilepsies. We first discuss work in drug-resistant epilepsy syndromes, that is, temporal lobe epilepsy, related to mesiotemporal sclerosis (TLE), and extratemporal epilepsy (ETE), related to malformations of cortical development. While these are traditionally conceptualized as ‘focal’ epilepsies, many patients present with broad structural and functional anomalies. Moreover, the extent of distributed changes contributes to difficulties in multiple cognitive domains as well as affective-behavioral challenges. We also review work in idiopathic generalized epilepsy (IGE), a subset of generalized epilepsy syndromes that involve subcortico-cortical circuits. Overall, neuroimaging and network neuroscience studies point to both shared and syndrome-specific connectome signatures of dysfunction across TLE, ETE, and IGE. Lastly, we point to current gaps in the literature and formulate recommendations for future research. Epilepsy is increasingly recognized as a network disorder characterized by recurrent seizures as well as broad-ranging cognitive difficulties and affective dysfunction. Our manuscript reviews recent literature highlighting brain network substrates of cognitive and affective dysfunction in common epilepsy syndromes, namely temporal lobe epilepsy secondary to mesiotemporal sclerosis, extratemporal epilepsy secondary to malformations of cortical development, and idiopathic generalized epilepsy syndromes arising from subcortico-cortical pathophysiology. We discuss prior work that has indicated both shared and distinct brain network signatures of cognitive and affective dysfunction across the epilepsy spectrum, improves our knowledge of structure-function links and interindividual heterogeneity, and ultimately aids screening and monitoring of therapeutic strategies.