In amyotrophic lateral sclerosis (ALS), brainstem integrity is critical in the development of pseudobulbar affect.

Researchers of this study sought to discern the correlation between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. The study comprised 35 patients with ALS who underwent neuropsychological assessment, with a subset also undergoing brain imaging.

According to the results, the presence of pseudobulbar affect was appreciably higher in bulbar onset ALS. The researchers observed that the frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably, the study found that pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A (p = 0.04).

Similarly, the researchers noted that only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem and mean fractional anisotropy of the superior cerebellar peduncles (all p < 0.01). Hierarchical regression indicated brainstem imaging in combination with site of symptom onset explained 73% of the variance in pathological laughter frequency in ALS.

“The current findings suggest emotional lability is underpinned by degeneration across distinct neural circuits, with brainstem integrity critical in the emergence of pathological laughter,” the researchers concluded.

This study was published in Frontiers in Neurology.


Keywords: MRI, amyotrophic lateral sclerosis, brainstem, motor neuron disease, pathological laughter and crying, pseudobulbar affect