Early cortical alterations and neuropsychological mechanisms in amyotrophic lateral sclerosis.

OBJECTIVE

This study investigates the characteristics of cortical structural and functional alterations in amyotrophic lateral sclerosis (ALS) patients and their modulation of emotional and cognitive functions, as well as to discuss their diagnostic value in early-stage ALS.

METHODS

Fifty-nine ALS patients (28 in ALS 1 and 31 in ALS 2, categorized using King's College Staging) and 31 healthy controls were evaluated using multiparametric MRI, motor and neuropsychological assessments, and serum neurofilament light chain (NfL) levels. Mediation analyses were performed to examine how cortical alterations influence the relationship between emotional and cognitive functions. Support vector machine (SVM) classification models were constructed to assess the diagnostic utility of differential cortical parameters.

RESULTS

ALS 1 patients exhibited increased cortical thickness (CT) and functional activity in the cingulate and frontotemporal regions, correlating with neuropsychological performance and NfL levels. Mediation analysis revealed that perigenual and frontotemporal functional activity significantly modulated the relationship between depressive symptoms and cognitive function. SVM classification showed that the combined altered regions with Amplitude of Low Frequency Fluctuations (ALFF) model achieved slightly better performance (AUC = 0.853, 95 %CI: 0.687-1.000, p < 0.001) compared to CT (AUC = 0.779, 95 %CI: 0.587-0.972, p < 0.001), although both models showed limited efficacy in differentiating between ALS 1 and ALS 2 groups.

CONCLUSIONS

Cortical structural and functional alterations in ALS mediate the impact of depression on cognitive function, offering insights into the neuropsychological mechanisms of the disease and potential biomarkers for early-stage diagnosis.