Dataset Information

Speech network regional involvement in bulbar ALS: a multimodal structural MRI study.

ABSTRACT: Objective: To examine gray (GM) and white matter (WM) structural changes in regions of the speech network (SpN) in ALS patients with varying degree of bulbar disease. Methods: T1 and DTI images were obtained for 19 ALS participants and 13 neurologically-intact controls. Surface-based, volumetric, and DTI metrics were obtained for 6 regions-of-interest (ROIs) including the primary motor cortex (PMC), pars triangularis (parsT), pars opercularis (ParsO), posterior superior temporal gyrus (pSTG), and transverse temporal (TT). Disease-effects and brain-behavioral correlates between neuroanatomy and clinical measures of bulbar, limb, and overall disability were examined using linear models. Results: Structural changes were observed in the right oral and limb PMC and left ParsT, 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 pars opercularis (part of Broca's area). Grip strength and disease duration models were non-significant. Conclusions: The findings suggested that regions of the left-dominant SpN may be implicated in ALS and degeneration of these areas are related to bulbar disease severity. Involvement of regions that overlap across multiple connectomes such as Broca's area, however, may be dependent 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.

SUBMITTER: Shellikeri S

PROVIDER: S-EPMC6648678 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Speech network regional involvement in bulbar ALS: a multimodal structural MRI study.

Shellikeri Sanjana S Myers Matthew M Black Sandra E SE Abrahao Agessandro A Zinman Lorne L Yunusova Yana Y

Amyotrophic lateral sclerosis & frontotemporal degeneration 20190514 5-6

<i>Objective:</i> To examine gray (GM) and white matter (WM) structural changes in regions of the speech network (SpN) in ALS patients with varying degree of bulbar disease. <i>Methods:</i> T1 and DTI images were obtained for 19 ALS participants and 13 neurologically-intact controls. Surface-based, volumetric, and DTI metrics were obtained for 6 regions-of-interest (ROIs) including the primary motor cortex (PMC), pars triangularis (parsT), pars opercularis (ParsO), posterior superior temporal gy ...[more]

PMID: 31088163

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Project description:BackgroundALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker.ObjectiveThe objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations.MethodsAtlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients' data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed.ResultsThe whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter.ConclusionsThis study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.

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Dataset Information

Speech network regional involvement in bulbar ALS: a multimodal structural MRI study.

Publications

Speech network regional involvement in bulbar ALS: a multimodal structural MRI study.

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