# Brain metabolic connectivity in ALS due to C9ORF72 hexanucleotide expansion: a [18F]FDG-PET study

## TL;DR

This study uses PET scans to show distinct brain metabolism patterns in ALS patients with a specific genetic mutation compared to those without.

## Contribution

The study identifies unique metabolic connectivity patterns in C9ORF72-related ALS using [18F]FDG-PET imaging.

## Key findings

- C9-ALS patients showed hypometabolism in thalami and hypermetabolism in cerebellum and brainstem compared to ctrl-ALS.
- C9-ALS exhibited broader thalamus-cingulate cortex correlations and more extensive frontal negative correlations.
- The salience network is more involved in C9-ALS, suggesting a link to cognitive and behavioral control.

## Abstract

Our aim was to investigate brain metabolic connectivity, as assessed via [18F]FDG-PET, in ALS patients carrying the C9ORF72 expansion (C9-ALS).

We compared brain metabolism of C9-ALS and patients without mutations of the main ALS-related genes (ctrl-ALS) through the two-sample t-test model of SPM12. Metabolic clusters showing a significant difference between the two groups were used as seed regions for an interregional correlation analysis (IRCA) in each group to evaluate metabolic connectivity.

As compared to ctrl-ALS, C9-ALS showed a relative hypometabolism in bilateral thalamus and left precentral and postcentral gyri, and a relative hypermetabolism in bilateral cerebellum and brainstem. In the IRCA, a positive correlation was found between the thalamic seed region and the cingulate cortex, including its anterior part. This correlation was broader in C9-ALS than in Ctrl-ALS. A negative correlation between the thalamic seed region and the sensorimotor cortex was only found in C9-ALS. In the IRCA, based on the cerebellar/brainstem cluster, positive correlations with the seed region substantially represented autocorrelation in both groups. Negative correlation, which mainly included frontal cortices, was more extensive in C9-ALS than in Ctrl-ALS.

In the comparison with ctrl-ALS, C9-ALS showed a relatively lower metabolism in the thalami and a relatively higher metabolism in the brainstem and the cerebellum. As compared to ctrl-ALS, C9-ALS showed a predominant involvement of the salience network, which is related to cognitive and behavioural control. The cerebellum might be recruited to cope with cognitive impairment to a greater extent in C9-ALS than in ctrl-ALS.