When laughter is not laughter and crying is not crying

A Technion research team reports on new mechanisms of action of a drug for the treatment of uncontrollable laughing and crying situations

Emotional expressions that are not adapted to the reality and the real experience of the person and that are expressed as bursts of uncontrollable crying, laughter or anger, are recognized neurological phenomena in a variety of conditions and neurological diseases, such as: after a head injury, a stroke, ALS or multiple sclerosis (MS) .

An integrated research team of Prof. Ariel Miller and Prof. Hillel Perat and the student Guy Heiman from the Faculty of Medicine at the Technion studied the neural mechanisms and brain regions underlying the control of emotional expressions such as laughter and crying and the brain mechanisms of action of a drug to relieve situations of uncontrollable crying, laughter or anger.

Using techniques that enable neurophysiological mapping of brain activity and the combination of emotionally charged stimuli (names of family members, etc.) and non-emotionally charged stimuli, the research team characterized motor and sensory brain areas, whose action is responsible for expressions of laughter and crying.

In the first phase of the study (which was published in JNS about a year ago), three groups were tested: healthy, multiple sclerosis patients and multiple sclerosis patients suffering from uncontrollable bursts of laughter and crying.

The research findings indicated the existence of a type of "Gate Mechanism" for a neurophysiological "emotional threshold". Stimuli that succeed towards the "emotional threshold" trigger brain electrical activity that manifests itself in laughter, crying or anger, even if the stimulus does not have a corresponding emotional charge. Thus, in people with emotional lability - a low emotional threshold - even stimuli without funny or sad content may lead to uncontrollable bursts of laughter and crying.

The researchers reported the similarity between the "emotional gate mechanism", or "emotional threshold", to another gate mechanism, known for a long time, which is the "gate mechanism" responsible for the "pain threshold". Support for the similarity between the mechanisms of the "emotional threshold" and the "pain threshold" in the nervous system was received following the fact that the Neurodex drug was found to have a positive effect in clinical trials both in reducing pain and in reducing abnormal emotional expressions.

Until today, the accepted assumption was that the syndrome of uncontrollable laughing and crying (PBA; IEED) is an uncontrolled manifestation of motor brain areas only, regardless of sensory components. And therefore, this phenomenon was included in the category of the group of disorders against the background of dis-inhibition - inability to inhibit motor expressions.

The current study, which was published in the journal J. Clinical Psyecho Pharmacology, is renewed in several aspects:

1. The study demonstrates that brain areas responsible for processing sensory data share together with motor brain areas in emotional expressions.

2. The study demonstrates that in patients with PBA (uncontrollable laughter and crying) - even very mild sensory stimuli (compared to the situation in healthy people) may activate brain areas responsible for emotional expressions. That is, patients with PBA have a low "emotional threshold". Therefore, any stimulus, even the lightest, will penetrate the "gate" and cause a chain reaction that will manifest itself in laughter or crying, even if the stimulus was not funny or sad. For example, people can burst out laughing or crying from any slight stimulus of stress, anxiety, excitement - even if the stimulus is not funny or sad.

3. The study demonstrated that using the drug Neurodex reduces neural hypersensitivity (raises the emotional threshold), in such a way that mild stimuli will not "bomb" the brain and will not lead to uncontrollable emotional outbursts.

In an international multicenter clinical trial whose positive results were published about a year ago, in the neurological scientific journal Annals of Neurology, a new drug called Neurodex (Neurodex; Zenvia) was tested. The drug works by blocking, among other things, the NMDA neurotransmitter.

Treatment with a daily pill of this medicine resulted in a noticeable relief in the phenomenon of excessive emotional expressions among multiple sclerosis patients and a very significant improvement in their quality of life. At the same time, it was observed that the patients with the drug received considerable relief from neuropathic pain that was their lot.

The study was conducted in a joint initiative with Prof. Ariel Miller, director of the Center for Multiple Sclerosis and Brain Research at the Carmel Medical Center and the Technion, and with an international team of researchers and the pharmaceutical company Avanir from San Diego.

Following this study and other accompanying studies, it is expected that the approval of the US health authorities (FDA) will soon be received for the widespread use of the drug Neurodex/Zenbia for these symptoms in a variety of neurological diseases.

It should be noted that until today there were no other drugs that were able to significantly reduce emotional manifestations of this type. Therefore there is great hope that the Neurodex drug; Zenvia will be approved for use both in a variety of neurological diseases in which there are manifestations of emotional outbursts such as controlled laughter and crying and for the relief of neuropathic pain.

On the same topic on the science website:

• Not only humans laugh
• A new drug called "Neurodex" significantly reduces bursts of uncontrollable laughter and crying among multiple sclerosis patients