What part of the brain is affected by Pseudobulbar Affect (PBA)?

From the Guidelines

Pseudobulbar Affect (PBA) primarily affects the cerebro-ponto-cerebellar pathways in the brain, which connect the cerebral cortex to the brainstem and cerebellum. This neurological condition results from damage to these neural pathways that normally control emotional expression. Specifically, PBA involves disruption to the connections between the frontal lobe (responsible for emotional control) and the brainstem and cerebellum (which regulate the motor aspects of emotional expression) 1. This disconnection leads to the characteristic symptoms of inappropriate, uncontrollable laughing or crying episodes that don't match how the person actually feels. PBA commonly occurs secondary to neurological conditions like stroke, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis (ALS), or dementia, all of which can damage these crucial pathways. The FDA-approved treatment for PBA is a combination medication of dextromethorphan and quinidine (Nuedexta), which works on neurotransmitter systems in these pathways to help regulate emotional expression 1. Some key points to consider in the management of PBA include:

• Assessment for mood swings and other mood disorders using tools like the Pathological Laughing and Crying Scale and the Center for Neurological Study-Liability Scale 1
• Cognitive and emotional therapy, psychotherapy, and support groups as part of a comprehensive treatment plan 1
• The importance of patient and family education to address the emotional and psychological impacts of PBA 1
• The potential for pharmacotherapy, including antidepressant medication, in managing symptoms of PBA, especially when they interfere with rehabilitation or patient relationships 1

From the Research

Brain Regions Affected by PBA

The brain regions affected by Pseudobulbar Affect (PBA) are not fully understood, but several studies provide insights into the possible areas involved.

• The most influential theory on PBA posits that emotional outbursts are being generated in the brainstem autonomously due to loss of regulatory control by the frontal lobes 2, 3.
• Another theory suggests that PBA is caused by the disruption of a corticopontine-cerebellar circuit that governs the modulation of emotional response 4.
• The limbic system may also be involved, as dextromethorphan, a medication used to treat PBA, is a sigma-1 receptor agonist, and these receptors are widely distributed in the limbic system 3.

Neurological Conditions Associated with PBA

PBA is commonly diagnosed secondary to primary neurological disorders, including:

• Amyotrophic lateral sclerosis
• Multiple sclerosis
• Traumatic brain injury
• Stroke
• Alzheimer's disease
• Parkinson's disease 5, 4, 6

Treatment and Management

Treatment of PBA typically involves pharmacological interventions, such as:

• Dextromethorphan/quinidine (DM/Q)
• Tricyclic antidepressants
• Selective serotonin reuptake inhibitors
• Anticonvulsants like divalproex 2, 3, 5, 4, 6