1 / 23

MCSA Journal Club February 2019

This journal club presentation discusses the white matter alterations in frontotemporal dementia (FTD) and their relationship with cognitive decline. The study analyzes data from the Frontotemporal Lobar Degeneration Neuroimaging Initiative to explore the disconnection syndrome hypothesis and understand the impact of white matter microstructure on cognitive function in FTD variants.

rickiev
Download Presentation

MCSA Journal Club February 2019

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MCSA Journal ClubFebruary 2019 Presented by: Mélissa Savard

  2. White Matter Alterations and Cognitive Loss in Frontotemporal Dementia Data from : Frontotemporal Lobar Degeneration Neuroimaging Initiative

  3. Background Prevalence • 1-26 per 100000 • 3-26 % early onset dementia (< 65y) Neuropathology • neuronal loss, gliosis, and microvacular changes Genetic • Familial history (40%), • Autosomal dominant (10%) Proteinopathy • microtubule-associated protein tau (MAPT) • TAR DNA-binding protein with molecular weight 43 kDa (TDP-43) • Fused-in-sarcoma (FUS) protein

  4. Symptoms are overlapping amongst variants

  5. GM and WM alteration in FTD (Agosta et al. 2015) GM (VBM) WM (FA) bvFTD N=14 • WM damage is more extensive than GM damage • Protein propagation would result in a convergence of damage to the core (frontal) network, with differences (amongst variant) due to the focal site of onset svPPA N=12 nfvPPA N=11 Core Network

  6. Aims Using Diffusion Weighted Imaging (DWI): • Extend the understanding of WM microstructure in FTD variants and it’s relationship with cognition • Explore the disconnection syndrome hypothesis • Instead of being localized in specific regions of the brain, higher functions resulted from associative (WM) connections between brain regions (Wernicke (1874), Dejerine (1892), Geschwind (1965), etc...)

  7. How diffusion MRI works

  8. DWI method • Constrained Spherical Deconvolution (CSD) (Tournier2007) estimates a white matter fibre Orientation Distribution Function (fODF)

  9. Measures 1. Fixel-Based Analysis Non linear registration to template allows to get different White Matter Fibres measures -Step 1 : reorient fODF : Fibre Density (local measure) -Step 2 : modulate fODF : Fibre Cross-Section (macroscopic measure) Stats : -Test correlations between predictor and FD and FC across subject for each voxel -Correct for multiple comparisons (bootstrap + anisotropic clustering)

  10. Measure 2. Structural Connectivity 2. Filtering tracks ~ 300k 1. Seeding 20 M tracks 5. Structural Connectivity 4. Counting tracks GMi to GMi 3. Applying GM atlas GM regions GM regions

  11. Connectivity matrix stats • Run repeated GLMs across subjects for each connections • Correcting for multiple comparison (FDR < 0.05) Uncorrected T values T values (pass fdr) GM regions GM regions GM regions GM regions pass pass BrainNet Viewer Uncorrected T values (all connections)

  12. Demographics and cognitive measure • 1. California Verbal Learning test • Episodic verbal learning • Memory (encoding + retrieval) • 2. Maximum Digit recall Span • Verbal Ability • Executive function • 3. Verbal Fluency : N Correct Word • Working memory • Executive function

  13. Fiber Density and FTD variants (vs CN) • Overlapping damages in uncinate and inferior longitudinal fasciculi • BV > frontal WM • SV > hippocampal part of cingulum and temporal WM • PNFA > Corpus callosum and Fronto-Occipital fasciulus

  14. Fiber Cross-Section and FTD variants (vs CN) • Same as FD but more severe effect

  15. Regions affected : Left uncinate fasciculus, Inferior Longitudinal Fasciculus, hippocampal part of cingulum • Overlapping fibres responsible for both short and long term recall ?

  16. Regions affected : Central part of Corpus callosum + Fronto-occipital fasciculus

  17. Regions affected : Superior longitudinal Fasciculus, Inferior Fronto-occipital fasciculus (animal only), some central corpus callosum ( d words only).

  18. Connectivity and FTD Variants *ipsilateral connections only : 20 % more affected is shown medTC x supTC infTC x thalamus fusiform x infTC latOFC x supTC ... Insula x Pars orbitalis Insula x Pars opecularis rmidFC x thalamus Caudate x putamen ... Insula x pars orbitalis infTC x thalamus Insula x pars triangularis Insula x pars opercularis ...

  19. Connectivity and cognition*ipsilateral connections only : 20 % more affected is shown VF : animal Insula x Pars opercularis infTC x thalamus VF : d words midTC x supFC pars orbitalis x thalamus VL : 30 sec infTC x thalamus SupTC x latOFC VL : 10 min delay SupTC x latOFC infTC x thalamus DS: Forward supFC x Supramarginal midFC x SupFC DS: Backward supFC x midFC supFC x midTC

  20. Summary • Fibre cross section (FC) appears more affected than fibre density (FD) • Demyelination? • Larges association fibres damages were associated lower cognitive scores • Uncinate fasciculus • connects hippocampus and amygdala to orbitofrontal cortex • Inferior Longitudinal Fasciculus • Connects anterior temporal lobe and the extrastriate cortex of the occipital lobe, • Object, face and place processing, reading, lexical and semantic processing, emotion processing, and visual memory. • Cingulum (hippocampal part) • connects to the hippocampus • takes memory information and integrates this to other parts of the brain • Corpus callosum • connects the left and right cerebral hemispheres • Fronto-occipital fasciculus • Structural connectivity adds information about disconnection between specific GM areas • Insula x Pars Opercularis (part of Brocas area) disconnection strongly associated to BV and PNFA variants and to worse verbal fluency • Inf. temporal gyrus x thalamus disconnection strongly associated to SV and PNFA variants and to worse verbal learning and verbal fluency • Sup. temporal gyrus x lat orbitofrontal disconnection strongly associated to SV variants and to worse verbal learning • Frontox parietal and interhemisperic (not shown) disconnection strongly associated to worse digit span • How to combine regional GM info to structural connectivity ??

  21. Same mutation can cause different disease ??

  22. Connectivity-based fixel enhancement

More Related