Temporal lobe epilepsy affects spatial organization of entorhinal cortex connectivity

Abstract

Evidence for structural connectivity patterns within the medial temporal lobe derives primarily from postmortem histological studies. In humans and nonhuman primates, the parahippocampal gyrus (PHg) is subdivided into parahippocampal (PHc) and perirhinal (PRc) cortices, which receive input from distinct cortical networks. Likewise, their efferent projections to the entorhinal cortex (ERc) are distinct. The PHc projects primarily to the medial ERc (M-ERc). The PRc projects primarily to the lateral portion of the ERc (L-ERc). Both M-ERc and L-ERc, via the perforant pathway, project to the dentate gyrus and hippocampal (HC) subfields. Until recently, these neural circuits could not be visualized in vivo. Diffusion tensor imaging algorithms have been developed to segment gray matter structures based on probabilistic connectivity patterns. However, these algorithms have not yet been applied to investigate connectivity in the temporal lobe or changes in connectivity architecture related to disease processes. In this study, this segmentation procedure was used to classify ERc gray matter based on PRc, ERc, and HC connectivity patterns in 7 patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis (mean age, 14.86 ± 3.34 years) and 7 healthy controls (mean age, 23.86 ± 2.97 years). Within samples paired t-tests allowed for comparison of ERc connectivity between epileptogenic and contralateral hemispheres. In healthy controls, there were no significant within-group differences in surface area, volume, or cluster number of ERc connectivity-defined regions (CDR). Likewise, in line with histology results, ERc CDR in the control group were well-organized, uniform, and segregated via PRc/PHc afferent and HC efferent connections. Conversely, in TLE, there were significantly more PRc and HC CDR clusters in the epileptogenic than the contralateral hemisphere. The surface area of the PRc CDR was greater, and that of the HC CDRs was smaller, in the epileptogenic hemisphere as well. Further, there was no clear delineation between M-ERc and L-ERc connectivity with PRc, PHc or HC in TLE. These results suggest a breakdown of the spatial organization of PHg-ERc-HC connectivity in TLE. Whether this breakdown is the cause or result of epileptic activity remains an exciting research question.

Normal and Abnormal Sharp Wave Ripples in the Hippocampal-Entorhinal Cortex System: Implications for Memory Consolidation, Alzheimer's Disease, and Temporal Lobe Epilepsy

“…According to fMRI studies, both TLE and AD demonstrate reduced resting-state activity and functional connectivity within the default mode network (DMN), a cortical system that is most active during conscious rest, suggesting shared regional network dysfunction (Luo et al, 2011 ). Deficits of episodic memory are also frequent in TLE (Helmstaedter, 2002 ; Holler et al, 2020 ) and other neurological disorders known to specifically affect temporal lobe circuits (Derner et al, 2018 ; Kilias et al, 2018 ; Kuhn et al, 2018 ). Moreover, loss of MEC layer III neurons in TLE alters intrinsic membrane and synaptic properties within associated circuits, resulting in hyperexcitability (Tolner et al, 2007 ).…”

“…Moreover, loss of MEC layer III neurons in TLE alters intrinsic membrane and synaptic properties within associated circuits, resulting in hyperexcitability (Tolner et al, 2007 ). Typically, TLE is characterized by profound changes in hippocampal and parahippocampal network circuitry resulting in spontaneous recurrent seizures and interictal activity in both humans and animal models (Sidhu et al, 2013 ; Sloviter and Bumanglag, 2013 ; Kuhn et al, 2018 ).…”

Causal Discovery with Multi-Domain LiNGAM for Latent Factors

“…Besides, we found that our results also coincide with some current findings. For example, the relation CA3 → CA1 is declared connective in neuroscience (Song et al 2015); PRC → ERC and PHC → ERC are usually related to episodic memories, which suggest distinct roles in memory formation and retrieval (Kuhn et al 2018); and ERC → CA1 is supposed to correlate with memory loss (Kerchner et al 2012).…”

A comparative study of pre‐alpha islands in the entorhinal cortex from selected primates and in lissencephaly

“…The EC integrates sensory information for memory and learning as well as conscious integration of external input and output. It is involved in brain diseases, including temporal lobe epilepsy, Down's syndrome, schizophrenia, Rett syndrome, Huntington's disease, progressive supranuclear palsy, argyrophilic grain disease, Parkinson's disease, dementia, and Alzheimer's disease (AD) (Braak & Braak, 1992Braak & Del Tredici, 2015;Braak et al, 2000;Hof et al, 1995;Kuhn et al, 2018;Leontovich et al, 1999;Mann & Esiri, 1989;Wakabayashi et al, 1994).…”