Approximately one-third of patients with epilepsy have a drug-resistant form of the disease. But even in cases where the pharmacological treatment is effective, it is common for side-effects of anti-epileptic drugs to arise, including skin rashes, dizziness, liver damage, psychiatric symptoms, cognitive impairment, and pregnancy-associated complications.
Surgery has a good rate of success in achieving long-term remission of epilepsy symptoms, but the number of patients undergoing surgery still represents a small percentage of patients with drug-resistant epilepsy.
Therefore, alternative, non-pharmacological treatment options are sought after. Music therapy is one of them.
The “Mozart effect”
The therapeutic potential of music has been widely investigated in cognitive neuroscience. But in the specific case of epilepsy, this use of music as therapy is particularly fascinating due its dual effect.
As seen in Part 1 of the music and epilepsy diptych, on the one hand, music can induce seizures, in what is known as musicogenic epilepsy, but on the other hand, it may have a beneficial outcome, at least in some patients and with some specific melodies.
This ability of music in reducing neuronal discharges and in reducing seizures has been known for decades. The first studies used mainly pure tones or loud music stimulation to shorten the duration of seizures. But in 1998, Hughes and colleagues reported for the first time a therapeutic effect of Mozart’s music on patients with epilepsy; they demonstrated that Mozart’s Sonata for Two Pianos in D Major (K.448) exerted an acute effect on the amount of epileptic activity, both during and between seizures. They called it the “Mozart effect”.
Subsequently, various trials or case reports started using Mozart’s K.448 to reduce seizures, initially only in chronic epilepsy conditions, but recently also for acute epilepsy.
Beneficial effects of Mozart’s music have been reported even for patients who had already tried more than two types of antiepileptic drugs with no success; while drugs had failed to control their seizures, Mozart was able to significantly reduce or even completely abolish epileptic discharges.
The anti-epileptic effect of Mozart’s music has also been supported by animal studies, where it has been shown to reduce the frequency of spontaneous seizures in rats.
These studies were reviewed in a meta-analysis by Dastgheib and colleagues published in 2014 summarizing the effects of Mozart’s music on epilepsy. The authors found that 84% of the examined patients exhibited significantly reduced epileptic discharges following Mozart music therapy. Still, there have been some accounts of the opposite effect; in some cases, despite being a clear minority, Mozart’s music actually led to an increase in seizures.
But the positive effect of Mozart does not appear to be exclusive to that particular sonata. For example, recent studies have found that, in addition to Mozart’s K.448, also Mozart’s K.545 could reduce epileptic discharges.
The mechanisms of music’s effects
The mechanisms by which Mozart may act as an anticonvulsant are unknown. This effect has been attributed to fundamental elements of music such as its rhythmic structure and its lower harmonics. These characteristics may somehow activate neuronal networks by evoking neuronal patterns with anticonvulsant properties.
This is in line with computational studies showing that neuronal networks are differentially affected by different sound frequencies – certain frequencies have seizure-inducing effects, while others can prevent seizure activity.
This dual effect of music may also be connected to a dual effect of dopamine. Stimulation of dopamine D2 receptors appears to be anticonvulsant, whereas dopamine D1 receptor activation appears to lower the seizure threshold both clinically and in animal models.
It is possible that music exposure may lead to a dopamine release and, consequently, to an upregulation and activation of D2 receptors, thereby acting as an anticonvulsant. By opposition, the proconvulsant effect of music, as seen in musicogenic epilepsy, may occur as a result of an emotional response – through increased release of dopamine in the prefrontal cortex, limbic dopamine responses may be suppressed, leading to the propagation of seizures.
Music and motor systems
An alternative (or complementary) explanation lies in the link between music and motor systems. Motor system modulation has been observed to change during auditory stimulation. The connection between music and motor function is evident in all facets of musical activity: dancing requires movement; playing musical instruments requires specific movements; singing requires moving our mouth and larynx.
In EEG studies evaluating the impact of cognitive tasks on the onset of seizures, it was found that tasks involving motor pathways were more likely to induce seizures, whereas spatial thinking tasks (calculations) produced an antiepileptic effect.
It has been proposed that music, language and motor functions may have a common neuronal substrate. This is supported by studies of language disorders where children with dyslexia, for example, show specific associated music, motor and language impairments that are improved with music lessons.
These music-related motor and language skills appear to be able to modulate the activity of the mirror neuron system. The mirror neuron system has been associated with numerous functions including action and intention understanding, language, self-awareness, and emotion; it may be able to integrate and process these different modalities of information, giving them meaning and emotion.
There is growing evidence that music plays a role in cognitive development, emotion regulation and social interaction. The human mirror neuron system has been proposed to underlie some of those effects, linking music perception, cognition and emotion. Music can invoke motor representations of emotions by recruiting the insula, a neural relay between the limbic and motor systems. Action, language and music appear to share neuronal pathways, and it has been proposed that the common features of these functions may be represented within the mirror neuron system.
These proposed mechanisms of music therapy are still highly theoretical. Nevertheless, it is possible that music therapy may provide a new non-invasive, non-pharmacological treatment for epilepsy.
References
Dastgheib SS, Layegh P, Sadeghi R, Foroughipur M, Shoeibi A, & Gorji A (2014). The effects of Mozart’s music on interictal activity in epileptic patients: systematic review and meta-analysis of the literature. Current neurology and neuroscience reports, 14 (1) PMID: 24272274
Hughes JR, Daaboul Y, Fino JJ, & Shaw GL (1998). The “Mozart effect” on epileptiform activity. Clinical EEG (electroencephalography), 29 (3), 109-19 PMID: 9660010
Liao H, Jiang G, & Wang X (2015). Music therapy as a non-pharmacological treatment for epilepsy. Expert review of neurotherapeutics, 15 (9), 993-1003 PMID: 26196169
Lin LC, Juan CT, Chang HW, Chiang CT, Wei RC, Lee MW, Mok HK, & Yang RC (2013). Mozart K.448 attenuates spontaneous absence seizure and related high-voltage rhythmic spike discharges in Long Evans rats. Epilepsy research, 104 (3), 234-40 PMID: 23395627
Lin LC, Lee MW, Wei RC, Mok HK, Wu HC, Tsai CL, & Yang RC (2012). Mozart k.545 mimics mozart k.448 in reducing epileptiform discharges in epileptic children. Evidence-based complementary and alternative medicine : eCAM, 2012 PMID: 23304207
Maguire M (2015). Music and its association with epileptic disorders. Progress in brain research, 217, 107-27 PMID: 25725912
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