Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.
Eur J Neurol
; 31(6): e16266, 2024 Jun.
Article
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| MEDLINE
| ID: mdl-38469975
ABSTRACT
BACKGROUND AND PURPOSE:
Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region.METHODS:
We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation.RESULTS:
Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds.CONCLUSIONS:
Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Imagen por Resonancia Magnética
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Pulvinar
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Proteína C9orf72
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Esclerosis Amiotrófica Lateral
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Mutación
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Neurol
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia