Speech Network Regional Differences in Bulbar Amyotrophic Lateral Sclerosis: Neuroimaging and Neuropathology Investigations

Bulbar ALS has devastating consequences on survival and quality of life, and may be linked to increased burden of extramotor deficits. This dissertation is comprised of three studies addressing the goal of better understanding the neural anatomical underpinnings of bulbar Amyotrophic Lateral Sclerosis (ALS) with a particular focus on the cortical speech network (SpN). The work has significant impact on ALS subtyping which is crucial for understanding disease pathogenesis, and clinical implications for diagnosis, prognosis, and recruitment into clinical trials. The first study characterized structural abnormalities in the SpN regions with relation to bulbar motor dysfunction using T1 and DTI neuroimaging in 16 patients with bulbar ALS. The results revealed left-lateralized differences in extramotor SpN regions with thinning in left inferior frontal gyrus (IFG) and diffusivity abnormalities underlying left primary auditory cortex (PAC) and posterior superior temporal gyrus (pSTG). Greater bulbar motor dysfunction was associated with greater structural abnormalities in selected SpN regions, while limb and disease severity were not. The second study systematically reviewed and compared published neuropathology data between bulbar-onset ALS (bALS) and spinal-onset ALS (sALS) in order to distinguish bulbar from spinal ALS. Neuropathology in IFG and pSTG were variable in bALS cases, however consistently spared in sALS. A subset of bALS cases also showed widespread tauopathy. Study three compared the anatomic distribution and types of neuropathology between 3 groups, namely: 3 bALS cases, 3 sALS with antemortem bulbar dysfunction (sALSwB), and 3 sALS without antemortem bulbar dysfunction (sALSnoB). SpN regions were most severely and extensively affected in the bALS cases, followed by sALSwB cases. Neuropathology in SpN regions was absent in sALSnoB cases. Two of the three bALS cases presented with atypical proteinopathy. Findings from the studies suggested that cortical SpN may be exclusively affected in bulbar ALS. The extent and severity of damage in SpN regions may be related to the severity of bulbar motor disease. Further, bALS may be associated with unique morphology and co-existing proteinopathy.

Department dc:contributor.department

Rehabilitation Science

Year dc:date.issued

2019

Author dc:creator

• Shellikeri, Sanjana

Advisor dc:contributor.advisor

• Yunusova, Yana

• Amyotrophic lateral sclerosis
• MRI
• neuroanatomy
• neurodegenerative
• neuropathology
• speech

Handle dc:identifier.uri

http://hdl.handle.net/1807/97636

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/97636