Poster E58, Thursday, August 22, 2019, 3:45 – 5:30 pm, Restaurant Hall
Speech Network in Bulbar ALS: structural neuroimaging and post-mortem neuropathological examination
Yana Yunusova1,2,3, Sanjana Shellikeri1,2, Sandra E. Black2,4,5,6, Lorne Zinman2,4,5, Julia Keith4,7;1Department of Speech-Language Pathology & Rehabilitation Sciences Institute, University of Toronto, 2Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 3University Health Network: Toronto Rehabilitation Institute, 4Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, 5L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, 6Rotman Research Institute, Baycrest, 7Department of Laboratory Medicine and Pathobiology, University of Toronto
Amyotrophic Lateral Sclerosis (ALS) is a multi-system disorder with motor and extramotor changes, characterized by progressive motor degeneration and behavioural and cognitive-linguistic deficits. Bulbar ALS is a subtype that affects speech production and may be associated with a greater burden of cognitive-linguistic deficits. The speech network (SpN) is a set of motor and extramotor structures involved in the production and processing of speech. The SpN encompasses the ventral portion of the primary motor cortex (oral PMC), as well as the ventral premotor cortex, posterior superior temporal gyrus (pSTG), inferior frontal gyrus (IFG; both, pars triangularis (ParsT) and pars opercularis (ParsO)), primary auditory cortex (i.e., Heschl’s gyrus of the transverse temporal cortex (TT)), parietal-temporal junction, insula, and cingulate cortex, as well as subcortical structures. This project investigates neuroanatomical changes in regions of the SpN in bulbar ALS using in vivo structural neuroimaging and post-mortem neuropathology. It was hypothesized that the degree of bulbar motor impairment would be associated with changes in the SpN regions, beyond the PMC (Study 1). It was also hypothesised that these differences would be observed in the neuropathological presentation of the disease (Study 2). For study 1, T1 and DTI images were obtained for 19 ALS participants and 13 controls. Surface-based, volumetric, and DTI metrics were obtained for 6 regions of the SpN including the oral PMC, ParsT, ParsO, pSTG, and TT. Structural changes were observed in the grey matter (GM) of right oral and limb PMC and left ParsT, as well as white matter (WM) underlying left TT and pSTG in ALS. Bulbar motor dysfunction was associated with WM abnormalities in the right oral PMC and left pSTG, and GM changes in bilateral TT. In contrast, symptom progression rate predicted GM and WM changes in bilateral ParsO. Grip strength and disease duration models were non-significant. For study 2, regions of the SpN within the left brain and brainstem were histologically assessed in 3 cases with bulbar-onset ALS (bALS), 4 cases with spinal-onset ALS and antemortem bulbar dysfunction (sALSwB), and 3 cases with spinal-onset without bulbar dysfunction (sALSnoB). Histological examination revealed degenerative changes in the frontal and temporal regions part of the SpN exclusively in bulbar variants (bALS and sALSwB). TDP-43 staging revealed differences in the anatomic distribution and severity of pathology between subtypes; bALS presented with the most severe and widespread SpN changes, followed by sALSwB. SpN regions were spared in sALSnoB cases. These findings suggest that regions of the left-dominant SpN are affected in ALS, and degeneration of these areas is related to bulbar disease severity. Regions that overlap across multiple connectomes, such as the IFG, may degenerate based on the rate of disease progression. The work contributes to our understanding of bulbar ALS subtype, which is crucial for predicting disease progression, delivering targeted clinical care, and appropriate recruitment into clinical trials.
Themes: Speech Motor Control, Disorders: Acquired
Method: White Matter Imaging (dMRI, DSI, DKI)