If you have seen the movie ‘Joker’ in theatres, there is a big chance you will recognise the card as the one carried around by the film’s main character, Arthur Fleck (better known as The Joker), who suffers from a variety of mental illnesses. One of his conditions causes him to have involuntary and extreme outbursts of (horrifying) laughter at the most inappropriate moments. But what is the real-life condition behind the Joker’s laugh?
The outbursts of laughter displayed by the movie are actually based on a type of emotional disturbance called Pseudobulbar Affect (PBA), a condition that typically occurs among patients with certain neurological disorders and brain injuries. In reality, PBA cannot only be portrayed by episodes of abrupt laughing, but also crying or displays of anger. In fact, outbursts of crying are more common, which is why PBA is often misdiagnosed as a mood disorder . These involuntary eruptions can variate from a subtle chuckle or sob to an abundant episode lasting up to several minutes and are not linked to one’s underlying emotional state. In individuals with PBA, their internal mood does not match the effect, which refers to the way emotions are demonstrated to the outside environment. They experience emotions normally, but express them in an exaggerated way, at inappropriate moments, since the laughing and/or crying are almost impossible to stop .
The pathophysiology behind PBA is not fully known, but the condition is almost always associated with neurological disorders or injuries that cause brain damage, such as Alzheimer’s disease, Parkinson’s disease and epilepsy ￼[1, 2]. It is hypothesised that neural disease or brain injury cause disruption of the neural networks that control motor output and emotions and can change chemical signals of pathways in the brain that are important for suitable outward emotional display. This neural dysfunction leads to activation of ‘laughing or crying pathways’ in the brainstem. Several studies also show that decreased levels of the neurotransmitter’s serotonin, norepinephrine and dopamine in cortico-limbic and cerebellar pathways are associated with PBA, whereas the same goes for increased levels of glutamate [2, 3].
To reduce the frequency and severity of emotional outbursts, PBA can be treated with tricyclic antidepressants and selective serotonin reuptake inhibitors. Another option for medication is dextromethorphan hydrobromide and quinidine sulphate, which is specifically designed to treat PBA.  Still, further research is needed to establish individualised treatment strategies for those who experience impairment in social or occupational functioning. 
So, even though PBA is oversimplified in The Joker, it is a consisting condition that people suffer from. Thus, if you ever encounter someone who starts crying or laughing uncontrollably out of nowhere, there probably is no reason to be frightened. Unless the person in question is actually dressed up like a clown. Maybe then, you should make a run for it.
 Mack, E., et al. Pseudobulbar Affect. Archives of Physical Medicine and Rehabilitation 95, 1599-1600 (2014).
 Finegan, E., et al. Pathological Crying and Laughing in Motor Neuron Disease: Pathobiology, Screening, Intervention. Front Neurol 10, 260-260 (2019).
 Hammond, F.M., et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurology 16, 89 (2016).