PSEUDOBULBAR AFFECT (PBA) & THE BRAIN

Pseudobulbar Affect (PBA) is a neurologic condition, not a psychiatric disorder
PBA involves the dysregulation of expression or affect and not feelings or mood. This is one way that distinguishes this condition from a psychiatric disorder. In PBA, expression refers to changes in autonomic functions and skeletal movements related to laughing and/or crying. 1 While laughing and crying presentation in PBA can look normal, many patients are unable to prevent the behavior or stop an episode voluntarily once it has happened. They may feel like they are crying for no reason or laughing out of the blue.
Laughing and crying in PBA is involuntary, sudden, and frequent and can be exaggerated in relation to the stimulus or incongruent with the patient’s underlying mood. 2
PBA occurs secondary to other neurologic conditions or brain injuries, including but not limited to stroke, dementia or Alzheimer’s disease, traumatic brain injury (TBI), Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Brain damage that results from various neurologic conditions like these may disrupt the neural networks and neurotransmitter activities that regulate emotional expression. This disruption may contribute to PBA episodes.3,4
PBA’s Mechanism of Disease
PBA can be treated with NUEDEXTA, which is believed to modulate certain neurotransmitter functions. 3, 8
Learn more about NUEDEXTA pharmacology
Brain lesions can affect control over emotional expression 4

Normal Brain Response
- In the normal functioning of the corticopontine-cerebellar (CPC) network, a stimulus results in normal emotional expression. 4
- The cerebellum modulates an emotional expression based on a stimulus to ensure an appropriate reaction, such as crying when something is sad.
- Brain stem areas relay information and activate somatic and visceral motor responses. 2, 4, 5

Abnormal Brain Response
- Lesions to any part of one or more areas of the CPC network can affect emotional expression. 4
- When neurotransmitter activities along damaged neural pathways are interrupted, it may contribute to PBA episodes of uncontrollable laughing and/or crying. 2
- Because information may be relayed incorrectly, laughing and crying episodes can be independent or in excess of a meaningful stimulus. 2
Glutamate is thought to be one of the major neurotransmitters involved in PBA 2
N-methyl-D-aspartate (NMDA) is one of the main neurotransmitter receptors for glutamate. 2 Glutamate receptors, including NMDA, exist throughout the brain and are also found in the neural network where PBA is thought to arise. 2, 6

Normal Glutamate Signaling
Glutamate receptors, such as NMDA, are responsible for facilitating many neurologic functions, including emotional expression. 4, 7 Glutamate exerts its signaling function by binding to and activating receptor proteins. 6

Abnormal Glutamate Signaling
In a variety of neurologic conditions and brain injuries, including stroke and various neurodegenerative disorders, too much glutamate can be released, which can cause excessive activation of glutamate receptors, leading to abnormal neurotransmission and cell dysfunction. 6, 7