Brainstem Correlates of Pathological Laughter and Crying Frequency in ALS

Abstract

Pseudobulbar affect is a disorder of emotional expression commonly observed in amyotrophic lateral sclerosis (ALS), presenting as episodes of involuntary laughter, or crying. The objective of the current study was to determine the association between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. Thirty-five sporadic ALS patients underwent neuropsychological assessment, with a subset also undergoing brain imaging. The Center for Neurological Study Lability Scale (CNS-LS) was used to screen for presence and severity of pseudobulbar affect (CNS-LS ≥ 13) and frequency of PLC episodes. Presence of pseudobulbar affect was significantly higher in bulbar onset ALS (p = 0.02). Frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A (R2 = 0.14, p = 0.04). Similarly, only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem (R2 = 0.46, p < 0.01), and mean fractional anisotropy of the superior cerebellar peduncles (left: R2 = 0.44, p < 0.01; right: R2 = 0.44, 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.

Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage

“…Importantly, these 4 symptoms may be a consequence of other factors outside of depression, including pseudobulbar affect or the grief response. Interestingly, patients with bulbar onset ALS were more likely to experience severe "mood" disorders that may represent an increased rate of pseudobulbar affect as has been previously demonstrated (44). Similarly in FTD, reports have been varied with one metaanalysis reporting a rate of 33% but noted the heterogeneity in reporting measures with differences across caregiver, patient, objective and subjective measures.…”

Medulla oblongata volume as a promising predictor of survival in amyotrophic lateral sclerosis

“…Moreover, grey matter loss of the brainstem was found to be associated to pseudobulbar symptoms (e.g. pathological laughter and crying) ( Tu et al, 2021 ). However, to date, only one study has investigated the role of brainstem as a potential indicator of disease severity and the authors reported a significant positive correlation between diffusion tensor imaging (DTI) metrics of several white matter tracts (e.g.…”

A Short Compilation on Theories of Humor and Laughter

“…The amygdala and hippocampus, as part of the limbic system, are implicated in the human brain in the production of laughter (Blake, 2003;LaPointe, 1991). Disease or damage to these areas is recorded as testimonies of the www.worldwidejournals.com resulting pathological crying and laughter (Tu et al 2021;Parvizi et al 2001), failure to distinguish lies from jokes (Winner et al 1998), loss of sensitivity to verbal humor (Brownell et al 1983), as shown in cases of traumatic brain injury (Keegan, Suger & Togher, 2021). A combination of the Theory of Mind and Game Theory perspectives are combined as the inner eye theory of laughter (Jung, 2003).…”