Abstracts

Rationale: TLE is characterized by disrupted functional connectivity in the ipsilateral temporal lobe but also other regions in task-free fMRI. Since functional connectivity is influenced by the large scale anatomical structure, this disruption is typically explained by seizure associated structural damage. However, temporary functional disturbances, e.g. interictal spikes, also impair connectivity. The overall goal of this study was to investigate stationary and dynamic functional connectivity with graph analytical measures that allow analysis of fully connected networks with positive and negative weights to test the hypotheses that TLE is associated with functional connectivity disturbances that are: 1. Paroxysmal and 2. Characterized by increased connectivity, i.e., the graph analytical signature of hypersynchronicity or interictal spikes.Methods: Task-free fMRI (2D EPI TR/TE: 2020/27 ms, 2.5x2.5x3.6 mm, 3x 8min acquisition) and structural imaging were acquired on a 3T MR in 10 patients with unilateral mesial-temporal TLE (mean age: 37.9±14.9) and 8 controls (mean age: 31.4±8.8). The fMRI was preprocessed in SPM12, conn 14p was used to extract the time series from 120 nodes encompassing 14 functional networks and 34 nodes in the mesial temporal region. Using a sliding window approach each 8 min scan was divided into 206 windows of 44 ms length and positive and negative strength for each window (dynamic) and the whole 8 min (stationary) calculated. Multiple one-tailed t-tests (FDR <0.05) were used to identify nodes with higher positive (PS) and lower negative strength (NS) in TLE than controls in the stationary analysis. Windows with simultaneous suprathreshold PS (≥mean in controls + 2 SD in controls) and subthreshold NS (≤mean in controls - 2 SD in controls) in mesial-temporal nodes and in cortical/subcortical or non-mesial nodes were determined for each runResults: Stationary: Mean non-mesial PS (11.9±1.6 vs 11.2±1.6) but not mesial PS (9.8±1.1 vs 9.4±1.1) was higher in TLE than in controls (11.9±1.6 vs 11.2±1.6). Nodes with high PS/low NS were identified in the left and right anterior mesial, inferior and superior temporal region, left and right insula, posterior cingulate and right supramarginal region. Dynamic: 60% of the TLE and 29% of the controls had non-mesial highPS/lowNS windows (p=0.02). TLE had more non-mesial highPS/lowNS windows than controls (median 5 (0-47) vs 0 (0-51) (p=0.03). The two groups did not differ in regard to mesial highPS/lowNS windows.Conclusions: We found evidence for an increased positive functional connectivity in TLE at the expense of the negative connectivity within temporal-lateral, limbic and insular, but not mesial-temporal regions in the stationary analysis that was caused by phases of diffuse increased connectivity within non-mesial nodes in the dynamic analysis. The latter finding should to be further investigated with combined fMRI/EEG recordings. Since they were also found in some controls they are more likely to represent prolonged phases of hyperconnectivity/hypersynchronicity than spikes.