Structural and functional underpinnings of precentral abnormalities in amyotrophic lateral sclerosis

Background and purpose: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of both upper and lower motor neurons. Studies using various magnetic resonance imaging (MRI) analytical approaches have consistently identified significant precentral abnormalities in ALS, whereas their structural and functional underpinnings remain poorly understood. Methods: Using cortical thickness, fractional anisotropy (FA), and effective connectivity, we performed a multimodal MRI study to examine the structural and functional alterations associated with precentral abnormalities in patients with ALS (n = 60) compared with healthy controls (n = 60). Results: Cortical thickness analysis revealed significant cortical thinning in the right precentral gyrus (PCG), superior frontal gyrus, and superior temporal gyrus in patients with ALS. Tractwise white matter microstructure analyses revealed decreased FA in the tracts connected to the PCG cluster in patients with ALS involving the right corticospinal tract and the middle posterior body of the corpus callosum. Additionally, the cortical thickness of the PCG cluster was found to be positively correlated with FA of the tracts connected to the PCG cluster, suggesting that these two structural features are tightly coupled. Using spectral dynamic causal modelling, effective connectivity analysis among the three regions with cortical thinning revealed decreased self-inhibitory influence in the PCG cluster in patients with ALS, which might be an endophenotypic manifestation of an imbalance in inhibitory and excitatory neurotransmitters in this region. Conclusions: The present data shed new light on the structural and functional underpinnings of precentral abnormalities in ALS.

Automated summary

Using multimodal MRI, this study identified significant cortical thinning in multiple brain regions, including the right precentral gyrus, in ALS patients, along with alterations in white matter microstructure. The findings also indicated a tight coupling between cortical thickness and white matter integrity in the precentral gyrus cluster. Additionally, decreased self-inhibitory influence in the precentral gyrus cluster was observed in ALS patients, suggesting an imbalance in inhibitory and excitatory neurotransmitters in this region.