Computational Support, Not Primacy, Distinguishes Compensatory Memory Reorganization in Epilepsy

Abstract

AbstractTemporal lobe epilepsy (TLE) is associated with impairment in episodic memory. A substantial sub-group, however, is able to maintain adequate memory despite temporal lobe pathology. What has been missing from prior work in the cognitive reorganization is a direct comparison of TLE patients with intact/compensated status from those who are memory impaired and uncompensated. Little is known about the particular regional activations, functional connectivities (FC’s), and/or network reconfigurations that implement changes in the primary computations or the support functions that drive adaptive plasticity and compensated memory. We utilized task fMRI on 54 unilateral TLE patients and 24 matched healthy controls (HC) during performance of a paired-associate memory (PAM) task to address three questions: 1) what regions implement PAM in TLE, and do such regions vary as a function of good versus poor performance, 2) are there unique FC’s present during memory encoding that accounts for intact status through the preservation of primary memory computations or the supportive computations that allow for compensated memory responses, and 3) what features during memory encoding are most distinctive: is it the magnitude and location of regional activations, or the presence of enhanced functional connections to key structures such as the hippocampus? Results revealed a unique profile of non-ictal, non-dominant hemisphere regions (e.g., right posterior temporal regions) were most important to intact/compensated status in LTLE, involving both increased regional activity and increased modulatory communication with the hippocampi, all feature that was missing in impaired/uncompensated LTLE. The profile involved areas that are neither contralateral homologues to left hemisphere memory areas, nor regions traditionally considered computationally primary for episodic memory. None of these areas of increased activation or functional connectivity were associated with advantaged memory in HC’s. Our emphasis on different performance levels yielded insight into two forms of cognitive reorganization. Computational primacy, where LTLE showed little change relative to HC’s, and computational support where Intact/Compensated LTLE patients showed adaptive abnormalities. The analyses isolated the unique regional activations and mediating FC’s that implement truly compensatory reorganization in LTLE. The results provided a new perspective on memory deficits by making clear that memory deficits arise not just from knockout of a functional hub, but from the failure to instantiate a complex set of reorganization responses. Such responses provided computational support to ensure successful memory. The findings demonstrated that by keeping track of performance levels, we can increase our understanding of adaptive brain responses and neuroplasticity in epilepsy.