Objective: Temporal lobe epilepsy (TLE) affects brain networks and is associated with impairment of episodic memory. Temporal and extratemporal reorganization of memory functions is described in functional magnetic resonance imaging (fMRI) studies. Functional reorganizations have been shown at the local activation level, but network-level alterations have been underinvestigated. We aim to investigate the functional anatomy of memory networks using memory fMRI and determine how this relates to memory function in TLE. Methods: Ninety patients with unilateral TLE (43 left) and 29 controls performed a memory-encoding fMRI paradigm of faces and words with subsequent out-of-scanner recognition test. Subsequent memory event-related contrasts of words and faces remembered were generated. Psychophysiological interaction analysis investigated task-associated changes in functional connectivity seeding from the mesial temporal lobes (MTLs). Correlations between changes in functional connectivity and clinical memory scores, epilepsy duration, age at epilepsy onset, and seizure frequency were investigated, and between connectivity supportive of better memory and disease burden. Connectivity differences between controls and TLE, and between TLE with and without hippocampal sclerosis, were explored using these confounds as regressors of no interest. Results: Compared to controls, TLE patients showed widespread decreased connectivity between bilateral MTLs and frontal lobes, and increased local connectivity between the anterior MTLs bilaterally. Increased intrinsic connectivity within the bilateral MTLs correlated with better out-of-scanner memory performance in both left and right TLE. Longer epilepsy duration and higher seizure frequency were associated with decreased connectivity between bilateral MTLs and left/right orbitofrontal cortex (OFC) and insula, connections supportive of memory functions. TLE due to hippocampal sclerosis was associated with greater connectivity disruption within the MTL and extratemporally. Significance: Connectivity analyses showed that TLE is associated with temporal and extratemporal memory network reorganization. Increased bilateral functional connectivity within the MTL and connectivity to OFC and insula are efficient, and are disrupted by greater disease burden.
Bibliographical noteFunding Information:
This work was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre (UCLH BRC; grant number 229811), The Wellcome Trust (grant number 083148), the Wellcome Trust Innovation Program (106882/Z/15/Z and 218380/Z/19/Z), and the Medical Research Council (G0802012, MR/M00841X/1). L.C. acknowledges support from a Brain Research UK PhD scholarship (award 14181). M.K.S. is supported by the UCLH BRC and Epilepsy Society.
We are grateful to the Epilepsy Society for supporting the Epilepsy Society MRI scanner, and to all the participants who participated in this research study.
© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
- psychophysiological interaction