Abstracts

Rationale: In previous work we found that the resting state functional connectivity in temporal lobe epilepsy (TLE) decreases with duration of disease in a temporal lobe network ipsilateral to the seizure focus [Morgan in press]. In this study, we expanded our investigation to include a second midline network thought to be involved in secondary generalization of seizures from the temporal lobe [Morgan in press, Holmes 2013, Blumenfeld 2009]. Functional connectivity was measured as a function of frequency to determine whether specific frequency components were responsible for the relationship to duration of disease in each network. Methods: Resting functional MRI data were acquired for 20 minutes in 14 TLE patients and 14 age and gender matched healthy controls. Regional signals were extracted from a temporal lobe network consisting of hippocampus, insula, and thalamus ipsilateral to the seizure focus and a midline network consisting of the ipsilateral and contralateral thalamus, the mid cingulate gyrus, and the precuneus. Wavelet coherence analyses of each network based on the method described by Chang and Glover [2010] and algorithms by Grinsted A., et al. [2004] were implemented yielding matrices of coherence (R²) and phase angle (θ) for each frequency at each time sample. Functional connectivity was computed as R²•real(e^iθ), and converted to a Z statistic using the Fisher Z transform. These Z values were averaged over the acquisition time, resulting in a metric that describes the functional connectivity between regions at each frequency (FC_f). This is a more detailed analysis than the typical resting state functional connectivity measure which is averaged over a frequency range. Then each FC_f of the matched control was subtracted from each patient. At each frequency, the linear correlation between FC_f (patient-control) and duration of disease across subjects was calculated resulting in an r and p-value. Frequencies where the p-value exceeds 0.05 indicate significant frequencies of the relationship. Results: The functional connectivity of the ipsilateral network decreased linearly with duration of disease at approximately 0.006-0.019 Hz and 0.072-0.086 Hz (Figure 1, blue). Interestingly, in a subset of the other frequencies (0.04-0.054 Hz) the thalamus-cingulate-precuneus connectivity increased linearly with duration of disease (Figure 1, red). The FC_f averaged over the significant frequencies vs. duration of disease are shown for each network (Figure 2). Conclusions: The wavelet coherence analysis revealed specific frequencies of the fluctuations that decrease with duration of disease (p=0.0024) in the ipsilateral seizure network, while other frequencies are increased with duration of disease in a midline network (p=0.03) in these TLE patients. A focused investigation of the physiological relevance of these frequencies may lead to elucidating the mechanism of how repeated seizures disrupt functional activity leading to behavioral and cognitive impairments in TLE. [Funded by NIH R01 NS75270 - VLM]