High energy consumption characterizes abnormal brain state transitions in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) patients experience shifts between non-seizing and seizing brain states, but the structural networks underlying these transitions remain undefined and poorly characterized. We detected dynamic brain states in resting-state fMRI and constructed linked structural networks utilizing multi-shell diffusion-weighted MR data. Leveraging network control theory, we interrogated the structural data for all possible brain state transitions, identifying those requiring abnormal levels of transition energy (low or high) in TLE compared to matched healthy participants (n's = 25). Results revealed three transitions requiring significantly higher energy in TLE; no abnormally low-energy transitions were observed. In HPs, transitions relied on mediator regions that did not belong to the initial source or final target brain areas. TLE transitions involved a more restricted set of source/target regions, predominantly outside the epileptogenic temporal lobe. Our findings highlight the abnormal and inefficient network mechanisms that accrue from the network entrainment inherent to TLE seizure activity. We argue these findings clarify the pathologic effects and help explain the well-known cognitive inefficiencies and other deficits found in the TLE disorder. • We used structural brain networks to assess the minimum energy required for transitioning between brain states in temporal lobe epilepsy (TLE). Our data captured three brain state transitions that required significantly higher energy in TLE patients compared to healthy participants. • Healthy participants exploited mediator regions for transitioning between states. In contrast, TLE patients utilized a limited set of source/target regions during transitions, mostly located outside the epileptogenic temporal lobe. • Our findings suggest that seizure-related network entrainment in TLE can lead to abnormal and inefficient mechanisms for network transitions, potentially explaining the cognitive inefficiencies and other deficits associated with the disorder.