Study of functional and structural connectivity and its relationship with memory deficits in patients with mesial temporal lobe epilepsy

Author(s)

Tamires Araujo Zanão

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2020-07-31

Examining board members

Fernando Cendes; Carlos Eduardo Soares Silvado; Rachel Paes Guimarães; Luiz Eduardo Betting; Marcondes Cavalcante Franca Junior

• Advisor: Fernando Cendes

Abstract

Introduction: The most common subtype of focal epilepsy is Mesial Temporal Lobe Epilepsy (MTLE) and hippocampus sclerosis (HS) is the most common lesion in MTLE. In addition, about 20% of patients with MTLE do not show abnormal magnetic resonance (MRI) signals (MRI-negative). Important differences exist between the MTLE subgroups when considering the presence and side of HS. Among the "resting state networks", the "Default Mode Network" (DMN) has a brain system comprising regions of the posterior cingulate cortex, medial prefrontal and medial, lateral, and inferior parietal cortices, cerebellum, and mesial temporal lobe. Evidence suggest involvement of the hippocampus in the functioning of DMN, indicating that memory may be incorporated into the cognitive processing of DMN. In addition to functional damage, seizures can cause microstructural damage to the white matter. Neuroimaging studies suggest that MTLE can affect beyond the hippocampus and temporal lobe. Among the highlighted tracts we analyzed fractional anisotropy of cingulum bundle, arcuate fascicle and inferior longitudinal fascicle. The fractional anisotropy can indicate the integrity of white matter. These fascicules are of special interest because they are directly connected (cingulum) or closely connected (arcuate and inferior longitudinal fasciculus) to the temporal lobe. Evidences suggest the involvement of these tracts in cognitive functions frequently impaired in MTLE, as memory. Investigation of memory alterations, combined with DMN analyzes and fractional anisotropy alterations in the WM can bring enlightenment of particularities and patterns of functional and structural impairments in patients with MTLE, with and without HS. Objectives: To investigate the relationship between functional DMN connectivity and the microstructural integrity by diffusion tensor image (DTI) and memory disorders in patients with MTLE, divided into right-HS, left-HS and MRI-negative. Methods: Clinical data were collected, and patients underwent to evaluation for confirming the diagnosis of MTLE. They were classified in group with right-HS, left-HS or MRI-negative. Healthy controls should not have previous neurological or neuropsychological diseases or contraindication to undergo to MRI acquisition. All participants underwent MRI and all patients and part of the controls participated in neuropsychological assessment. For DMN the seed method was used in the posterior cingulate cortex, and for the correlation with neuropsychological data ROIs were added in the right and left hippocampus and right and left parahipocampal gyrus. We analyzed fractional anisotropy of cingulum, arcuate and inferior longitudinal fasciculus and correlated the values with neuropsychological data. Results: Our study provided evidence that MTLE disrupts the functional connectivity of DMN, with reduced recruitment of the hippocampus within groups with HS. There was also exacerbated connectivity in regions related to DMN for the right-HS and MRI-negative groups. In comparison with controls, all groups of patients performed worse for visual memory and IQ, and groups with HS for verbal memory. We did not find the same pattern of DMN in the correlations with neuropsychological tests. In the microstructural integrity analysis (DTI), our results suggest that HS is hierarchically related to the impairment of fractional anisotropy, and the left-HS group presented generalized bilateral impairment in all analyzed tracts; followed by the HS-right group with reduced fractional anisotropy only in the ipsilateral hemisphere for cingulum and ILF, without impairment for arcuate. Discussion and conclusion: The exacerbated connectivity in regions related to DMN for the HS-right and RM-negative groups probably involves a compensatory organization, while the left-HS group was not able to functionally connect with regions adjacent to the DMN network. The presence of HS can interfere in the ipsilateral correlations between DMN (posterior cingulate cortex seed-based) and neurocognitive tests, with cognitive impairments wider than expected by lateralization, differing from the literature, which associates worse verbal memory performance with left-HS, and visual to right-HS. HS is also associated to fractional anisotropy impairment. In general, the RM-negative group showed fractional anisotropy values similar to the controls, in line with the idea that the absence of HS is associated with less damage to white matter. The mechanisms involved in the loss of white matter integrity differ between the MTLE groups, resulting in different consequences for cognition (AU)

• FAPESP's process: 16/10433-0 - Study of functional and structural connectivity and its relationship with memory deficits in patients with mesial temporal lobe epilepsy
• Grantee: Tamires Araujo Zanão Mariano
• Support Opportunities: Scholarships in Brazil - Doctorate