Toward a more precise, clinically--informed pathophysiology of pathological laughing and crying

Area of Science:

• Neuroscience
• Neurology
• Psychiatry

Background:

• Involuntary emotional expression disorder (IEED) encompasses pathological laughing and crying (PLC) and emotional lability (EL).
• Understanding the underlying pathophysiology is crucial for diagnosis and treatment.
• Existing literature on lesions, epilepsy, and brain stimulation provides insights into IEED mechanisms.

Purpose of the Study:

• To update the pathophysiology of IEED by integrating findings from lesion, epilepsy, and brain stimulation studies.
• To propose a revised model of the neural circuitry involved in volitional and emotional expression.
• To offer a criterion-based nosology for subtypes of PLC and EL.

Main Methods:

• Comprehensive review of existing literature on brain lesions, epilepsy, and brain stimulation studies related to IEED.
• Analysis of neuroanatomical pathways, including corticopontine projections and their targets.
• Examination of neurochemical receptor systems involved in regulating emotional expression.

Main Results:

• A dual-system model of IEED pathophysiology is proposed: a volitional system (frontoparietal) inhibiting an emotional system (frontotemporal).
• Specific brain regions and pathways involved in both volitional control and emotional expression are identified.
• Neurotransmitter systems (glutamatergic, cholinergic, GABAergic, dopaminergic, serotonergic) and their roles in regulating the periaqueductal gray (PAG) are detailed.
• Lesions in the volitional pathway can lead to PLC, while direct activation of the emotional pathway may cause EL and epilepsy-related emotional outbursts.

Conclusions:

• The updated pathophysiology provides a framework for understanding IEED.
• A clear distinction between PLC and EL based on distinct neural pathway involvement is suggested.
• The proposed nosology aims to improve the classification and clinical management of IEED subtypes.