Abstracts

Rationale: There are currently no functional imaging based markers for treatment response in temporal lobe epilepsy (TLE). In this study, we investigated if there is an association between resting state functional connectivity (RsFC) and medical tractability in temporal lobe epilepsy (TLE).  Methods: We enrolled 47 TLE patients and healthy controls to undergo resting state functional magnetic resonance imaging (fMRI). Patient medical records were assessed for seizure activity and EEG reports were screened for side and location of seizure focus. RsFC measurements were derived from each subject and results were compared between groups of normal controls (NCs, n=13), treatment responsive, medically tractable cases of TLE (MedTract, n=15), and treatment-resistant, intractable cases of TLE (Intract, n=19), controlling for age at time of scan and duration of epilepsy in the patient group. Results: Significant differences between groups were detected in several measures of RsFC. Due to the lack of medically controlled right-sided TLE cases and to control for potential confounders and differences that could be due to location side of seizure focus, we performed all analyses on left sided TLE cases only (MedTract left TLE, n=10), (Intract left TLE, n=10). These analyses demonstrated significant decrease in RsFC between thalamus and hippocampus, bilaterally in intractable left TLEs (for the two structures within the left hemisphere: r= -0.5, p= 0.023; for the two structures within the right hemisphere: r= -0.6, p= 0.013), as well as increased RsFC between left thalamus and left amygdala in medically tractable left TLEs (r= -0.6, p= 0.034). Further, we observed significant differences in RsFC strength between the medial prefrontal cortex (mPFC) and the remaining 163 ROIs across the rest of the brain. RsFC was increased in intractable left TLEs when compared to medically tractable left TLEs (r= -0.8, p= 0.014), as well as when intractable left TLEs were compared to normal control subjects (r= -0.9, p= 0.005) (Figure 1).    Conclusions: Our results demonstrate differences in resting state functional connectivity network patterns between medically tractable and intractable TLE cases. These findings are consistent with prior findings of abnormal thalamocortical stuctural connectivity measures in TLE (Barron et al 2014) and suggest that thalamocortical pathway abnormlities may serve as a marker for treatment resitsance. Early identification of TLE patients who are likely respond poorly to pharmacological treatment may benefit from earlier surgical interventions.  Funding: Sources of funding: The Epilepsy Study Consortium (ESCI) is a non-profit organization dedicated to accelerating the development of new therapies in epilepsy to improve patient care. The funding provided to ESCI to support HEP comes from industry, philanthropy and foundations (UCB Pharma, Eisai, Pfizer, Lundbeck, Sunovion, The Andrews Foundation, The Vogelstein Foundation, Finding A Cure for Epilepsy and Seizures (FACES), Friends of Faces and others). The project described was furthermore funded in part by The Morris and Alma Schapiro Fund, as well as grant #UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program.