Pathological laughing and crying in amyotrophic lateral sclerosis is related to frontal cortex function

Abstract

The syndrome of pathological laughing and crying (PLC) is characterized by episodes of involuntary outbursts of emotional expression. Although this phenomenon has been referred to for over a century, a clear-cut clinical definition is still lacking, and underlying pathophysiological mechanisms are not well understood. In particular, it remains ill-defined which kind of stimuli-contextually appropriate or inappropriate-elicit episodes of PLC, and if the phenomenon is a result of a lack of inhibition from the frontal cortex ("top-down-theory") or due to an altered processing of sensory inputs at the brainstem level ("bottom-up-theory"). To address these questions, we studied ten amyotrophic lateral sclerosis (ALS) patients with PLC and ten controls matched for age, sex and education. Subjects were simultaneously exposed to either emotionally congruent or incongruent visual and auditory stimuli and were asked to rate pictures according to their emotional quality. Changes in physiological parameters (heart rate, galvanic skin response, activity of facial muscles) were recorded, and a standardized self-assessment lability score (CNS-LS) was determined. Patients were influenced in their rating behaviour in a negative direction by mood-incongruent music. Compared to controls, they were influenced by negative stimuli, i.e. they rated neutral pictures more negatively when listening to sad music. Patients rated significantly higher on the CNS-LS. In patients, changes of electromyographic activity of mimic muscles during different emotion-eliciting conditions were explained by frontal cortex dysfunction. We conclude that PLC is associated with altered emotional suggestibility and that it is preferentially elicited by mood-incongruent stimuli. In addition, physiological reactions as well as behavioural changes suggest that this phenomenon is primarily an expression of reduced inhibitory activity of the frontal cortex, since frontal dysfunction could explain changes in physiological parameters in the patient group. We consider these findings being important for the clinical interpretation of emotional reactions of ALS patients.

Neuropsychiatric Symptoms of Multiple Sclerosis: State of the Art

“…However, it is considered to be a disconnection syndrome, which results in the loss of brainstem inhibition in a putative control center on crying and laughter [58]. It is also associated with greater cognitive deficits mediated by the frontal lobe [59]. Usually it is more frequent among patients with greater physical incapacity and in more advanced stages of the illness [2].…”

Pseudobulbar affect as a negative prognostic indicator in amyotrophic lateral sclerosis

“…Survival analysis was performed on a total of 94 cases. 25 The study of Floeter and coworkers showed that patients with ALS and PBA presented disruption of descending fiber tracts from the frontotemporal cortex toward the pons. Demographic and clinical parameters of the cohort considered for the analysis, along with group comparisons according to CNS-LS total score (</≥13), are reported in Table 1 tern of the disease.…”

“…Another hypothesis is that PBA may be related to frontal cortex dysfunction. 25 The study of Floeter and coworkers showed that patients with ALS and PBA presented disruption of descending fiber tracts from the frontotemporal cortex toward the pons. 21 Frontal circuits are also involved in executive and social cognition deficits, both common in ALS and both related to a poorer prognosis.…”

Resting state fMRI analysis of pseudobulbar affect in Amyotrophic Lateral Sclerosis (ALS): motor dysfunction of emotional expression

“…This condition may arise from the disconnection of brainstem structures from cortical inhibition and can occur in several neurological diseases, such as strokes, traumatic brain injuries, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and primary lateral sclerosis (PLS) (Finegan et al, 2019 , 2021 ; Parvizi et al, 2006 , 2009 ; Work et al, 2011 ). At the population level, up to 50% of patients with motor neuron diseases, and in particular those with bulbar upper motor neuron (UMN) involvement, are affected by this condition, and one-third of ALS patients present PBA at diagnosis (Tortelli et al, 2016 ; Hübers et al, 2016 which represents a negative prognostic symptom (Barć et al, 2020 ; Tortelli et al, 2018 ). However, although PBA is a frequent and long-reported symptom, it has remained unclear if this phenomenon is a result of a lack of inhibition from the frontal cortex ("top-down-theory") or due to altered processing of sensory inputs at the brainstem level ("bottom-up-theory") (Bede & Finegan, 2018 ).…”