Abstract
We have previously shown that the connectivity of the hippocampus to other regions of the default mode network (DMN) is a strong indicator of memory ability in people with temporal lobe epilepsy (TLE). Recent work in the cognitive neuroscience literature has suggested that the anterior and posterior aspects of the hippocampus have distinct connections to the rest of the DMN and may support different memory operations. Further, structural analysis of epileptogenic hippocampi has found greater atrophy, characterized by mesial temporal sclerosis, in the anterior region of the hippocampus. Here, we used resting state FMRI data to parcellate the hippocampus according to its functional connectivity to the rest of the brain in people with left lateralized TLE (LTLE) and right lateralized TLE (RTLE), and in a group of neurologically healthy controls. We found similar anterior and posterior compartments in all groups. However, there was weaker connectivity of the epileptogenic hippocampus to multiple regions of the DMN. Both TLE groups showed reduced connectivity of the posterior hippocampus to key hubs of the DMN, the posterior cingulate cortex (PCC) and the medial pre-frontal cortex (mPFC). In the LTLE group, the anterior hippocampus also showed reduced connectivity to the DMN, and this effect was influenced by the presence of mesial temporal sclerosis. When we explored brain-behavior relationships, we found that reduced connectivity of the left anterior hippocampus to the DMN hubs related to poorer verbal memory ability in people with LTLE, and reduced connectivity of the right posterior hippocampus to the PCC related to poorer visual memory ability in those with RTLE. These findings may inform models regarding functional distinctions of the hippocampal anteroposterior axis.
Highlights
Resting state functional connectivity has emerged as a potentially valuable tool for interrogating system integrity and predicting treatment outcome in neurological and psychiatric disease populations [1, 2]
There were no differences in age of onset, duration of epilepsy, verbal memory, visual memory or IQ, between the lateralized TLE (LTLE) and right lateralized TLE (RTLE) groups, all t < 1.5, p > 0.15, nor were there any differences between patient groups in presence or absence of MTS, distribution χ 2(1, N = 46) = 0.37, p = 0.5, in the presence of other lesions, χ 2(1, N = 46) = 1.1, p = 0.3, or in language dominance using Fisher’s exact probability test, p = 0.1
Using a k-means clustering procedure, we were able to segment the left and right hippocampus into anterior and posterior divisions in individuals with left and right TLE and healthy controls. This demonstrates that the functional connectivity fingerprints of the hippocampal voxels are sufficiently distinguished along the long axis in the patient population, regardless of the effects of temporal lobe epilepsy
Summary
Resting state functional connectivity has emerged as a potentially valuable tool for interrogating system integrity and predicting treatment outcome in neurological and psychiatric disease populations [1, 2]. The mPFC and PCC are known to be critical hubs for the DMN [14] and, given the biased connectivity along the long axis of the hippocampus, critical network properties may be missed if the hippocampus is treated as a homogenous region of interest. This long-axis distinction is of further importance because structural atrophy in the hippocampus is thought to be biased in people with TLE, with greater atrophy occurring in the head of the hippocampus compared to the body and tail measured on MRI [15], measured post-mortem [16], and on resected tissues [17]. Investigating hippocampal connectivity using this anterior and posterior hippocampal distinction has the potential to further elucidate network changes in TLE and how these hippocampal parcels might relate to memory impairments
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