Musicogenic Epilepsy: Can Sean Paul Really Cause a Seizure?

To many people, music provides escapism. It allows for the diversion of thoughts and, perhaps for some, the submission into emotional states of mind that we didn’t quite realise we were experiencing. However, for a small population of individuals, their relationship with music is essentially pathological due to the fact it triggers seizures. Termed musicogenic epilepsy, this condition is a rare form of complex epilepsy where patients report seizures that are induced by music. Described by a character in Coelho’s The Zahir as ‘an ecstatic experience provoked by hearing a particular kind of sound’, patients with musicogenic epilepsy can be sensitive to music of a particular genre, a particular instrument, or in extremely intriguing cases, a specific singers voice. Some patients have actually named the singer Sean Paul as a stimulus for their seizure activity, and can therefore no longer listen to his music (note – some may argue that this is not a shame) (Swaminathan, 2008).

Many people are aware that epilepsy is a condition where the neurons of the brain fire abnormal electrical signals, essentially resulting in an overload of electrical activity in the brain. There are numerous types of seizures that each present with different symptoms. Localisation of the excess electrical activity in the brain has allowed for scientists and clinicians to determine which types of seizures result from excess activity in particular brain regions. Frontal lobe epilepsy, for example, is the second most common type of epilepsy that can present as a partial seizure, i.e. the seizure is initially localised to just one hemisphere of the brain. As the frontal lobe of the brain contains many regions associated with motor function, tonic posture and clonic movements, such as facial grimacing and automatisms, are largely associated with seizures in this area of the brain (Schachter, 2013).

Musicogenic epilepsy (ME) has been assumed a rare condition due to the fact less than 200 cases have been reported; however clinicians argue that many epileptics may suffer from musicogenic seizures without actually realising it. Of the reported cases, it has been found that ME is increasingly common in individuals who are exceptional musicians and who possess sophisticated musical understanding. Our understanding of the physiological mechanisms underlying the triggered seizures has been enriched mainly by single case report studies. The ability to provoke seizures in patient’s known to have ME provides researchers with greater insight into the process of seizure initiation and propagation.

Such research includes the work of Mehta et al. (2009). The scientists conducted extensive research to discover the underlying brain regions involved in ME, adopting PET scans and EEG recordings to collect their data. An EEG recording is commonly used in clinical neurophysiology to confirm a patient is suffering from seizures. The test works by attaching many electrodes to various points of the scalp and recording a potential difference between select electrodes. This therefore allows the detection of abnormal electrical activity in the brain and also allows for localization of the activity. The participant for the study, a 24-year-old female, had been suffering from epilepsy for two years preceding her acknowledgement that music was a trigger.

In the study, three seizures were recorded during a period of 1 week. All three seizures were music provoked, and the pattern of spread across the brain was consistent. The PET scans showed the location of seizure onset as being in the right mesial temporal lobe – the lobe that contains the auditory cortex and so processes sound information. This was followed by sequential spreading to the parahippocampal gyrus and the amygdala, and eventually the lateral temporal lobe. These regions of the brain are extremely interesting, as they are largely associated with emotional processing – linking back to the previously mentioned idea that music is a form of escapism and allows us to uncover deeper emotions. As an approach to treatment, the case study participant underwent a right temporal lobectomy (in non-scientific terms this translates to ‘they removed the region of the brain found to be associated with the seizures’). The patient was discharged and upon follow up 9 months later was found to be seizure free and able to listen to the music that once initiated her seizures. That, in my opinion, is pretty remarkable neuroscience.

Evidently, it has to be taken into consideration that due to the small number of reported cases, the research surrounding ME remains fairly limited and is subject to critical review. However, studies such as work by Mehta et al (2009) are revealing more and more about the complexity of the condition, which, even if you may not consider yourself a scientist, is still absolutely fascinating! The seizures appear to be associated with the emotional and limbic processing of both sound and music, and onset predominantly favors the right hemisphere of the brain. Music is believed to induce a pattern of activity within a network of neurons in multiple brain areas, including the primary auditory cortex and association cortex. Such neurons then project to the hippocampus and amygdala regions where the memory of the music is stored in addition to the emotional response that we feel when we hear the music. One theory suggests that if this neuronal network coincides with that involved in a seizure of some description, then an association may form, resulting in greater likelihood of seizure activity upon activation of the neuronal network by repetition of the music. What weird and wonderful mischief the brain is capable of!

Author: Molly Campbell


Could optogenetics be the next best approach for those with untreatable epilepsy?

What is epilepsy?

Epilepsy is a neurological disorder that can cause the loss of consciousness or convulsions. These are associated with abnormal electrical activity of the neurons within the brain (1). It affects many people, and can be a difficult and frustrating disease to live with. It is common for the cause of the epilepsy to be unknown, however within infants it is common that high temperatures can trigger the epileptic seizures. This is due to their undeveloped hypothalamus, the temperature control centre of the brain. In some patients, absence seizures are common. These are where the individual has a sudden loss of activity and consciousness, which is quickly returned. In comparison, many individuals have partial seizures where one side of the brain is affected. Another type of seizure is the tonic clonic seizure – these are generalised and affect the entire brain. Both tonic clonic and partial seizures cause muscles to stiffen, the person loses consciousness and falls to the floor, and following this they usually jerk rhythmically. This often causes the individual to be confused once they awaken (2).

What is refractory epilepsy?

Many individuals that suffer from the disease can be treated with pharmacological drugs, which depress the over-excited neuronal activity within the brain. These pharmacological drugs often suppress their seizures. Sometimes this may require two or three drug combinations. Unfortunately, 20-30% of patients have what is called retractable epilepsy. This means that current drugs treatments and even combinations of pharmacological interventions cannot control their epilepsy. This can be extremely debilitating to the individual. It has been found that some people, who have treatable epilepsy at a younger age, can have a relapse, as they get older. Therefore, treatments often need to be changed to suit the individual. It is therefore common that someone can be treated well, and then develops refractory epilepsy (3).

What is optogenetics? 

Optogenetics has been known to be promising within pre-clinical trials and could be an upcoming treatment for those with refractory epilepsy. Optogenetics involves the use of light to control excitable neurons within the brain. Genes are manipulated within cells causing them to express light activated channels. These light activated channels are known as opsins, these include the photoreceptors, which we have in our own visual system. They deliver information by absorbing photons from light (8). One example is Halorhodopsin, a protein, which can be genetically inserted into cells. Halorhodopsin will cause inhibition of neural activity when activated by yellow light. These light activated proteins are placed into the neurons via viral carriers. If the virus is placed into the animal in early development then it will be passed onto the offspring of that cell, therefore all cells will be responsive to the light. This technique however, can be invasive, as a viral vector needs to be inserted and a device to deliver the light (5).

Evidence that optogenetics works

This has been trialed and tested in many rat and mice studies, and has had good results. Compared to other current treatments for refractory epilepsy, such as vagal stimulation, which have shown to be ineffective, optogenetics has a much higher promise of effect from pre-clinical trials (5). Berglind et al (2014) found that the epileptiform activity in the hippocampus of mice could be treated by optogenetics, as it showed inactivation of neurons within the hippocampus both in vitro and in vivo. Thus, providing evidence for the use of optogenetics (6).

Whilst optogenetics has shown promising results, the site of seizure initiation is usually unknown; therefore the target for optogenetic treatment may not always be clear (4). Soper et al (2016) found that optogenetic activation of the deep intermediate layers of the superior colliculous (the region of the brain mainly involved in directing eye movement towards a stimulus) suppressed seizures in the forebrain and brainstem models in rats (Figure 1). You can see that patient A after optogenetic stimulation has a lower amount of tonic seizure and clonic seizure responses. Patient B has a reduction in myoclonic jerks. Pentylenetetrazole (PTZ) was given to induce the seizures in the rats. This also suggests that the deep intermediate layers of the superior coliculous are areas of the brain suitable for targeting optogenetics (4).

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Figure 1: A1) Patient treated with PTZ and no optogentic stimulation. * myoclonic jerk, dashed line – clonic seizure response, solid line tonic seizure response. A2) The same subject with the same amount to PTZ but with 100 Hz optogentic stimulation. B1) A second subject treated with PTZ and no optogentic stimulation. Showing myoclonic jerks (*). B2) The same subject treated with PTZ and 100 Hz of optogenetic stimulation. (Soper et al 2016)

Optogenetics approach into human treatments

It is clear that the evidence for optogenetics is extremely recent and is therefore still a new approach undergoing experimentation, it may be some time before they are used in humans. Inserting these genetic modifications into human cells may have different results to those shown in rats and mice studies. It is thought that this could cause long-term changes to the brain so safety and toxicity needs to be studied. (7) Hopefully within the near future this treatment could be put to use to help those with drug-resistant and persistent epilepsy.

By Abigail Byford

Edited by Molly Campbell




4 Soper C, Wicker E, Kulick CV, N’Gouemo P, Forcelli PA. (2015) Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks. Neurobiol Dis. doi: 10.1016/j.nbd.2015.12.012.

5 Wykes, R. et al. 2016. Optogenetic approaches to treat epilepsy. Journal of Neuroscience Methods. 260,pp.215-220.

6 Berglind, F. et al. 2014. Optogenetic inhibition of chemically induced hypersynchronized bursting in mice. Neurobiology of Disease. 65,pp.133-141.