Temporal lobe epilepsy (TLE) can be conceptualized as a network disease. The network can be characterized by inter-regional functional connectivity, i.e., blood oxygen level-dependent (BOLD) signal correlations between any two regions. However, functional connectivity is not constant over time, thus computing correlation at a given time and then at some later time could give different results (non-stationarity). We hypothesized (1) that non-stationarities can be induced by epilepsy (e.g., interictal epileptic activity) increasing local signal variance and that (2) these transient events contribute to fluctuations in connectivity leading to pathological functioning, i.e., TLE semiology. We analyzed fMRI data from 27 patients with TLE and 22 healthy controls focusing on EEG-confirmed wake epochs only to protect against sleep-induced connectivity changes. Testing hypothesis (1), we identified brain regions where the BOLD signal variance was significantly greater in TLE than in controls: the temporal pole - including the hippocampus. Taking the latter as the seed region and testing hypothesis (2), we calculated the time-varying inter-regional correlation values (dynamic functional connectivity) to other brain regions and found greater connectivity variance in the TLE than the control group mainly in the precuneus, the supplementary and sensorimotor, and the frontal cortices. We conclude that the highest BOLD signal variance in the hippocampi is highly suggestive of a specific epilepsy-related effect. The altered connectivity dynamics in TLE patients might help to explain the hallmark semiological features of dyscognitive seizures including impaired consciousness (precuneus, frontal cortex), sensory disturbance, and motor automatisms (sensorimotor cortices, supplementary motor cortex). Accounting for the non-stationarity and state-dependence of functional connectivity are a prerequisite in the search for potential connectivity-derived biomarkers in TLE.
Keywords: EEG-fMRI; biomarker; functional connectivity; interictal epileptiform discharges; non-stationarity; seizure; semiology; temporal lobe epilepsy.