Cortical disconnection in temporal lobe epilepsy

A critical concept in neurology is cortical disconnection, in which seemingly normal gray matter can have reduced function due to loss of white matter (WM) connections. White matter damage has been extensively described in temporal lobe epilepsy (TLE), but the anatomical distribution of cortical disconnection in TLE is not fully characterized. Here, we studied 221 participants (64 left-TLE, 55 right-TLE, 102 controls) from three different epilepsy treatment centers. We employed a group connectometry diffusion imaging tractography approach to identify WM fibers with reduced integrity in TLE. We then assessed the anatomical distribution of the gray matter endpoint projections of abnormal fibers to map the anatomical pattern of disconnections. As expected, left- and right-TLE were associated with multiple WM pathways with reduced integrity, which were associated with extensive cortical disconnection involving predominantly limbic structures. Controlling for medial temporal gray matter atrophy, cortical disconnection of the left cingulum and the thalamus as well as disconnection of the bilateral putamen and the amygdala was associated with lower verbal memory immediate recall. In conclusion, our results support that cortical disconnection is an underappreciated but pervasive phenomenon in TLE, and cortical disconnection of limbic structures beyond the medial temporal regions is related to verbal memory performance.