012 Volumetric and connectivity profile of regional thalamic abnormality in amyotrophic lateral sclerosis

Objectives Neurodegeneration in ALS follows a diffuse pattern of cortical involvement.¹ We have previously highlighted that thalamic abnormality is a robust disease signature in ALS,² but the integrity of thalamic nuclei and their clinical association remains unclear. We employed a novel segmentation technique for thalamic nuclei and track-weighted functional connectivity (TW-sFC) to characterize volumetric and connectivity profiles of regional thalamic abnormality.

Methods Forty ALS patients and 27 age-and-education matched controls were recruited. All patients underwent comprehensive clinical examination and 3T MRI scan (T1; DWI; rs-fMRI). Thalamic nuclei were robustly segmented from T1 images using the THOMAS pipeline.³ Whole-brain white matter fibre tracking was performed using MRtrix and combined with resting-state fMRI to generate combined structural and functional connectivity maps (TW-sFC).⁴

Results Reduced thalamus volume was observed bilaterally in ALS compared to control (p values < 0.036). Bilateral volumetric reduction was consistently observed across all regions except for the anterior thalamus in ALS (p values < 0.05). Significant increased TW-sFC was observed in ALS in the right anterior thalamus (p =0.03) and right anterior ventral nuclei (p < 0.01). TW-sFC of the mediodorsal nuclei correlated with disease duration (p < 0.02) and disease progression rate (p < 0.03).

Conclusions Regional thalamic abnormalities are present in ALS and hold a significant association with clinical features. Variability in thalamic connectivity demonstrated significant clinical associations with disease duration, progression rate, and upper motor dysfunction. The findings reinforce that diffusion and functional MR imaging modalities are promising markers of disease burden in ALS.

References

1. Brettschneider J, Del Tredici K, Toledo J, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 2013;74:20–38.

2. Tu S, Menke R, Talbot K, Kiernan M, Turner M. Regional thalamic MRI as a marker of widespread cortical pathology and progressive frontotemporal involvement in amyotrophic lateral sclerosis. JNNP 2018;89:1250–1258.

3. Su J, Thomas F, Kaso W, et al. Thalamus optimized multi atlas segmentation (THOMAS): fast, fully automated segmentation of thalamic nuclei from structural MRI. Neuroimage 2019;194:272–282.

4. Calamante F, Smith R, Liang X, Zalesky A, Connelly A. Track-weighted dynamic functional connectivity (TW-dFC): a new method to study time-resolved functional connectivity. Brain Struct Funct 2017;222:3761–3774.