P 28 Voxel-based Morphometry (VBM) subcortical white matter changes correlate with disease progression in amyotrophic lateral sclerosis

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Abstracts / Clinical Neurophysiology 128 (2017) e305–e412

Corresponding author at: LMU, Neurology, München, Germany.

Introduction: A binary approach to resting-state functional connectivity based parcellation (fCBP) provides useful insights into human brain organization, but also entails oversimplifications (Glasser, 2016). This is especially true for multisensory and higherlevel associative brain areas, such as the bilateral vestibular cortical network with its multiple multisensory areas (Dieterich and Brandt, 2015). This study aimed to identify subunits of the vestibular cortex whilst accounting for a possible affiliation of voxel to different sensory systems using a multivariate fCBP within a vestibular region of interest (ROI) including known cortical areas of the vestibular network, i.e. vestibular informed masked fCBP. Methods: Resting-state functional magnetic resonance imaging (fMRI) data of 60 healthy volunteers, 30 left-handed (LH; 14 females; aged 20–65 years, mean age 26.1 ± 8.6 years) and 30 age- and gender matched right-handed (RH; 17 females; aged 20–67 years, mean age 26.7 ± 8.3 years) was used to first perform a binary vmasked functional connectivity based parcellation (fCBP) within a vestibular ROI (Lopez and Blanke, 2011). The subunits were then correlated (i) to each other and (ii) to whole-brain resting-state networks (RSN) and their behavioral interpretations (Laird, 2011). Results: Our approach revealed functional subunits, which were either ‘‘asymmetrical & less connected to RSN” (i.e. subunits within the inferior frontal gyrus (IFG; BA 44 & 45) and middle/posterior/ inferior insula) or ‘‘symmetrical and more connected to RSN” (e.g. subunits within the superior temporal gyrus (STG) or temporoparietal junction (TPJ)). Within these diverging subunits both ‘‘unique” voxels (= only present in 1 subunit) and ‘‘common” voxels (= part of multiple subunits) were distinguishable. Discussion: The data confirm a complex handedness-dependent bilateral vestibular network of multiple multisensory areas organized around a core region in the inferior, middle, and posterior insula (Dieterich, 2003). This core-region, whilst multisensory in nature, is hemisphere-dominant (asymmetrical) and functionally more specialized (less RSN-assigments). Its functional acolytes (e.g. STG, TPJ) surround it hemisphere-balanced (symmetrical), wellconnected (more RSN-assigments), and functionally tinged by the neighboring sensory systems (e.g. TPJ by visual system, STG by auditory system). Within these fundamentally different types of units there seem to be more integrative (‘‘common” voxels) and more disconnected (‘‘unique” voxels) subunits. Supported by the by the Society for the Advancement of Science and Research at the LMU, Graduate School of Systemic Neuroscience (GSN), the German Foundation for Neurology (Deutsche Stiftung Neurologie) and the German Federal Ministry of Education and Research (German Center for Vertigo and Balance Disorders IFBLMU, Grant code 01EO140). References Glasser MF et al. A multi-modal parcellation of human cerebral cortex. Nature 2016;536(7615):171–8. Dieterich M, Brandt T. The bilateral central vestibular system: its pathways, functions, and disorders. Ann NY Acad Sci 2015;1343:10–26. Lopez C, Blanke O. The thalamocortical vestibular system in animals and humans. Brain Res Rev 2011;67:119–46. Laird AR et al. Behavioral interpretations of intrinsic connectivity networks. J Cogn Neurosci 2011;23(12):4022–37. Dieterich M et al. Dominance for vestibular cortical function in the non-dominant hemisphere. Cerebral Cortex 2003;13(9):994–1007. doi:10.1016/j.clinph.2017.06.106

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VK and RB contributed equally to this work.

Poster P 28 Voxel-based Morphometry (VBM) subcortical white matter changes correlate with disease progression in amyotrophic lateral sclerosis—M. Batyrbekova 1,*, T. Prell 1, B. Stubendorff 1, M. Bokemeyer 2, V. Hartung 3, O.W. Witte 1 1 ( Uiniversitätsklinikum Jena, Hans-Berger Klinik für Neurologie, Jena, Germany, 2 Universitätsklinikum Jena, Department of Neuroradiology, Jena, Germany, 3 HELIOS Klinikum Gotha, Institut für Radiologie, Gotha, Germany) ⇑

Corresponding author.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive, multisystemic disorder.Signs of lower motor neurone involvement are readily detectable but the involvement of the upper motor neurone is elusive.Hence, we must identify the extent and development of ALS related changes in the brain in different subtypes of ALS to facilitate an early diagnosis and stratification for clinical trials. Previous studies applying Voxel-based morphometry (VBM) provided inconsistent results. Objective: The aim of this study is to describe the heterogeneity of ALS with regard to the site of onset (bulbar vs.limb), disease duration (long vs.short), degree of disability (high vs.low) and disease progression rate (rapid vs.slow) in a large cohort of well characterized ALS patients.ALS related MRI changes should correlate with clinical parameters, such as ALSFRS-R score and D50 (50% disease progression in a model of sigmoidal decay of the ALSFRS-R). The longterm aim of this study is to evaluate VBM as a predictive marker for ALS in a representative number of subjects (n > 100). Methods: High resolution T1-weighted FLASH 3D scans (fl3d) in 92 ALS patients and 62 healthy controls were analyzed using VBM8 in SPM8 on matlab 2009b.Clinical parameters were collected regularly: disease duration, date and location of the first symptom, rate of disease progression and degree of disability (ALSFRS-R). Based on these clinical parameters, patients were classified into the subgroups and analyzed to determine changes in the gray and white matter. Results: The mean age of 62 controls was 53.97y and of the 92 patients 60.24y.The patient group included 24 bulbar and 68 limb onsets.Average disease duration was 25 mo, wherein 26 patients had a long (P24mo) and 35 had a short (612mo) disease duration. Mean ALSFRS-R was 37.8.46 patients had a ‘‘low” degree of disability (ALSFRS-R P 40), whereas 17 patients were ‘‘highly” impaired (630). Mean progression rate was 0.66.A subgroup with a rapid form of ALS included 16 patients, with a slow form 46.Using VBM, more rapid progression, longer disease duration and more severely affected patients had a more pronounced reduction in GMV in the central, and frontal brain regions, whereas subcortical WM was more severely altered. Conclusion: Using VBM in high resolution T1 in a large cohort of ALS patients, we were able to identify the key regions of ALS pathology which correlated well with three clinical progression parameters.It is likely that previous studies were underpowered and ALS related heterogeneity obscured the relevant pathology in computerized voxel-based analyses. Acknowledgement: This research is supported by BMBF (Bundesministerium für Bildung and Forschung) in the framework of the E-RARE programme (PYRAMID) and JPND (OnWebDUALS and SOPHIA) of the European Union in collaboration with the Neuroimaging Society in ALS (NiSALS) MRI repository Jena. doi:10.1016/j.clinph.2017.06.107