A new comprehensive analysis on the effect of Mozart’s music on epilepsy has confirmed that listening to his piano music can reduce the frequency of epilepsy attacks.
The results of this comprehensive meta-analysis (a study of studies), which may overturn current skepticism about the effect, are presented at the ECNP congress after recent publication in a peer-reviewed journal.
The idea that listening to Mozart may have beneficial effects on mental health arose from early findings in the 1990s. There have been several studies since, but many involved small numbers of people, or have been of variable quality, leading to mixed evidence overall.
This has meant that the ‘Mozart Effect’ has been treated with some skepticism by many clinicians.
Now two Italian Researchers, Dr. Gianluca Sesso and Dr. Federico Sicca from the University of Pisa have conducted a systematic review of works related to the effect of Mozart’s music on epilepsy.
Working according to accepted standard methods for analyzing clinical treatment, they looked at 147 published research articles, which they then evaluated according to such things are relevance and quality of the research.
This allowed them to select 12 pieces of research which they gathered into 9 separate groups, representing the best available science on the effect of Mozart’s music on epilepsy.
They found that listening to Mozart, especially on a daily basis, led to a significant reduction in epileptic seizures, and also to a reduced frequency of abnormal brain activities in epileptic patients (called interictal epileptiform discharges, which are commonly seen in epileptic patients).
These effects occurred after a single listening session and were maintained after a prolonged period of treatment.
Gianluca Sesso said “This isn’t the first such review of the effect of Mozart’s music on epilepsy, but there has been a flow of new research in the last few years, so it was time to stand back and look at the overall picture.
The design of the studies varies, for example some people look at a single listening session, others at daily listening sessions, so it’s not easy to form a conclusion.
Epilepsy is surprisingly common, affecting just under 1 person in a hundred worldwide. This means that it has significant social and personal costs.
Mostly it’s treated by drugs, but these drugs don’t work in around 30% of patients, so we need to be open to other therapies: the important thing is that these therapies can be tested and shown to work, and this is what we have shown here”.
The meta-analysis indicates that a period of listening to Mozart can give an average reduction in epileptic seizures ranging from between 31% to 66%, but this varies from person to person and according to the music stimulus used.
The original studies on the Mozart Effect used the sonata for 2 pianos, K448, and this has remained the music most used in studies. The K545 piano sonata has also been shown to have an effect.
Dr. Sesso said, “All cultures have music, so it obviously fulfills some psychological need. The mechanisms of the Mozart Effect are poorly understood. Obviously other music may have similar effects, but it may be that Mozart’s sonatas have distinctive rhythmic structures which are particularly suited to working on epilepsy.
This may involve several brain systems, but this would need to be proven.
This is a review of research, and not original research. One thing it shows is that we need more consistent studies into the effect of music on the mind”
Commenting, Dr. Vesta Steibliene, Lithuanian University of Health Sciences, and member of the ECNP Abstract and Poster Committee commented, “There is growing interest in non-invasive brain stimulation techniques in the treatment of neuropsychiatric disorders.
This review revealed that Mozart music could be an effective non-invasive method of neurostimulation, reducing the frequency of epileptic seizures, even in hard to treat patients. However, in order to use this method in clinical settings, the exact mechanism of the Mozart music effect on the brain regions should be better understood”.
Dr. Steibliene was not involved in this work.
Music has been used for healing mental and physical diseases. Rauscher et al. report that brief exposure to Mozart’s Sonata for Two Pianos in D major, K.448 (Mozart K.448), produces a temporal increase in spatial reasoning scores [1], the so-called “Mozart Effect.”
In addition to improvement of cognitive function, subsequent studies reveal positive effects from listening to music for many medical diseases, including hypertension, anxiety, and dementia [2]–[4].
For example, Särkämö et al. investigated patients with strokes who listened to their favorite music for two months. Their results show that recovery in the domains of verbal memory and focus attention improved significantly more in the music group than in the control group, even six months after the stroke [5].
In patients with Parkinson disease, after listening to self-selected music, motor coordination with “Vienna Test System” shows improvement in aiming and line tracking [6]. This study provides evidence that specific music can improve the precision of arm and finger movement.
Relaxing classical music was also used in sleep disorders. 94 students with sleep complaints participated a music study. They listened to relaxing classical music, including some popular pieces from Baroque to Romantic, for 45 minutes every night at bedtime for 3 consecutive weeks, or audiobooks-a CD containing 11 hours of short stories by Hungarian writers such as Frigyes Karinthy, Gyula Krúdy, Géza Gárdonyi, Zsigmond Móricz and Mihály Babits for 45 minutes every night at bedtime for 3 consecutive weeks, or no intervention for 3 weeks.
The results show music significantly improves sleep quality according to the Pittsburg sleep quality index and depressive symptoms. However, sleep quality and depressive symptoms did not improve in the audiobook and control group [7].
Regarding epilepsy, Hughes et al. and our previous study show that epileptiform discharges decrease when listening to Mozart K.448 in patients with epilepsy [8, 9]. Furthermore, our study also reveals that listening to Mozart K.448 reduces seizure frequencies in children with intractable seizures [10].
The seizure recurrence rate after the first unprovoked seizure in pediatric patients is highly variable, depending on the follow-up period and patient selection. Age at onset of epilepsy under 1 year, remote symptomatic etiology, developmental delay/mental retardation, abnormal EEG background, frequent epileptiform discharges, and abnormal neuroimaging are all significant predictors of a higher risk for recurrence of epilepsy [11, 12].
Children with a recurrence have a similar epileptic outcome when compared to children presenting with multiple seizures, regardless whether they were treated after the first unprovoked seizure or not [13]. This argues in favor of withholding anti-epileptic drug treatment at least until a second seizure has occurred to reduce the potential for adverse effects of drugs, including unpleasant physical effects, adverse cognitive and behavioral changes, and potential teratogenicity [13, 14].
Until now, there has been no effective method to reduce seizure recurrence after the first unprovoked seizure. In this study, we investigated the effect of Mozart K.448 on the seizure recurrence in children with their first unprovoked seizure who have epileptiform discharges.
Discussion
Mozart K.448 listening is reported to diminish the intensity of tinnitus, improve the paper-folding and cutting tests in patients with mild cognitive impairment, and increase weight gain in preterm infants by reducing resting energy expenditure [15]–[17]. Regarding epilepsy, our previous works show that interictal discharges were reduced in most patients with epilepsy when they listened to Mozart K.448 [9].
In addition, 72.7% of the patients with refractory epilepsy became seizure free or had a very good response by listening to Mozart K.448 [10]. Our previous report also demonstrates that Mozart K.448 is not the only piece of music to have beneficial effects on children with epilepsy, and that listening to Mozart K.545 with similar lower harmonics can decrease epileptiform discharges in epileptic children as well [18].
In this current study, we investigated the effect of Mozart K.448 on seizure recurrence after the first unprovoked seizure. The results showed that listening to Mozart K.448 once daily reduced the seizure recurrence rate and epileptiform discharges.
The estimated seizure recurrence rate in the control group was 76.8%, while it was 37.2% in music treated patients. The epileptiform discharges also showed an approximate 70-80% reductions after 1, 2, and 6 months of music listening.
Seizure recurrence after the first unprovoked seizure in pediatric patients ranges from 26-71% [19]. Risk factors for seizure recurrence include a remote symptomatic etiology, an abnormal EEG, a seizure occurring while asleep, a history of prior febrile seizures, and Todd’s paresis [12].
In a large study, 564 patients, including adults and children who had first unprovoked seizures, have been followed up for 2–4 years. Sixty-seven percent of them had a recurrence within 12 months of the first seizure, and 78% had a recurrence within 36 months [20]. In the under the age of 16 group, the seizure recurrence rate was 83% by 36 months [20].
In our study, the seizure recurrence rate was estimated to be 76.8% by 24 months in the control group. An abnormal EEG and an age less than 16 appeared to be risk factors for a higher recurrence rate in our study. However, the seizure recurrence rate did not demonstrate a significant difference in patients with different gender, mentality, seizure type, and etiology.
The results were similar to our previous studies which show that gender, mentality, and etiology of epilepsy do not influence the short-term or long-term music effect on epileptiform discharges [9, 21].
The epileptiform discharges were significantly reduced in EEGs performed 1, 2, and 6 months after initiating music listening in patients without seizure recurrence. However, the epileptiform discharges did not decrease in a duration-dependence manner. EEG improvement after one month of listening to Mozart K.448 may serve as an indicator in determining the long term outcome of music intervention.
Although it is not possible to predict how long the patients should be treated, the effectiveness of music listening was demonstrable within one month and continued for at least 6 months. We suggest that listening to music daily for 6 months has a beneficial effect in decreasing seizure recurrence in children with first unprovoked seizures.
Recently, several theories have been introduced regarding the effects of sound on the brain. Poor health is reported to be associated with lower parasympathetic tone in several medical conditions, including epilepsy [22].
Lotufo et al. report a sympathovagal imbalance in epilepsy, as shown by lower high frequency (HF), the standard deviation of the RR interval (SDNN), and the square root of the mean squared differences of successive RR intervals (RMSSD) values when compared to controls [23].
One study shows that a two-hour music intervention in cancer patients increases their relaxation scores and parasympathetic activities [24].
Another study shows that forty-five minutes of music therapy once a week in patients with cerebrovascular disease enhances parasympathetic activities and decreases congestive heart failure events by reducing plasma cytokine and catecholamine levels [25].
Our previous data also demonstrates that significant increases in HF, RMSSD, the standard deviation of differences between adjacent RR intervals (SDSD), and a decrease in mean beats per minute in heart rate variability analysis occurs while listening to Mozart music in children with epilepsy.
At the same time, epileptiform discharges are significantly reduced during and right after listening to Mozart music. The results suggest that Mozart music stimuli induces parasympathetic activation [26]. It is possible that musical enhancement of parasympathetic tone may account for the beneficial effects on epilepsy.
Neurotransmitter pathways may also be involved in the effect of Mozart K.448 on epilepsy. Musical exposure is known to increase the expression of dopamine levels in the brain [2]. In recent years, the role of dopamine in the pathophysiology of epilepsy has been well documented. A Positron Emission Tomography study shows that impaired dopamine uptake in the midbrain is hypothesized to contribute to seizures in juvenile myoclonic epilepsy [27].
In a recent animal study, the authors report that pentylenetetrazole induced seizures decrease the dopamine levels in striatal and hippocampal areas, accompanying the induction and propagation of seizures [28]. It is possible that listening to music modifies the dopaminergic pathways contributing to the beneficial effects in epilepsy therapy.
There are limitations to this present study. First, the number of participants was somewhat limited and most of the patients were idiopathic in etiology. The statistical power is 0.74, under alpha error 0.05, based on 22 treatment and 24 control subjects with non-recurrence rates 0.63 and 0.23, respectively.
Although the power is not sufficient, our findings may provide preliminary evidence that Mozart K.448 listening is beneficial for children with first unprovoked seizures. Second, the lack of control music made it impossible to say that the effects were specific to Mozart K.448 or to a placebo effect.
Third, because we did not follow up the EEG in all patients in the control group, it could not be determined whether time duration itself could have caused the decreases in epileptiform discharges, although we had shown that there were significant decreases in epileptiform discharges after listening to Mozart K.448 in treatment group. Fourth, we used per protocol analysis with compliant patients instead of using intention-to-treat analysis, although the result of intention-to-treat is also significant (p = 0.029).
Conclusions
In conclusion, listening to Mozart K.448 reduced the seizure recurrence rate and epileptiform discharges in children with first unprovoked seizures, especially of idiopathic etiology. Although there were limitations to the case numbers in this study, the results highlight that Mozart K448 listening is a promising alternative treatment in patients with first unprovoked seizures and abnormal EEGs. More investigations should be performed to substantiate the effects of music on first unprovoked seizures.
References
- 1.Rauscher FH, Shaw GL, Ky KN: Music and spatial task performance. Nature. 1993, 365 (6447): 611-CAS Article PubMed Google Scholar
- 2.Sutoo D, Akiyama K: Music improves dopaminergic neurotransmission: demonstration based on the effect of music on blood pressure regulation. Brain Res. 2004, 1016 (2): 255-262. 10.1016/j.brainres.2004.05.018.CAS Article PubMed Google Scholar
- 3.Wu J, Chaplin W, Amico J, Butler M, Ojie MJ, Hennedy D, Clemow L: Music for surgical abortion care study: a randomized controlled pilot study. Contraception. 2012, 85 (5): 496-502. 10.1016/j.contraception.2011.09.018.Article PubMed Google Scholar
- 4.Han P, Kwan M, Chen D, Yusoff SZ, Chionh HL, Goh J, Yap P: A controlled naturalistic study on a weekly music therapy and activity program on disruptive and depressive behaviors in dementia. Dement Geriatr Cogn Disord. 2010, 30 (6): 540-546. 10.1159/000321668.Article PubMed Google Scholar
- 5.Sarkamo T, Tervaniemi M, Laitinen S, Forsblom A, Soinila S, Mikkonen M, Autti T, Silvennoinen HM, Erkkila J, Laine M: Music listening enhances cognitive recovery and mood after middle cerebral artery stroke. Brain. 2008, 131 (Pt 3): 866-876.Article PubMed Google Scholar
- 6.Bernatzky G, Bernatzky P, Hesse HP, Staffen W, Ladurner G: Stimulating music increases motor coordination in patients afflicted with Morbus Parkinson. Neurosci Lett. 2004, 361 (1–3): 4-8.CAS Article PubMed Google Scholar
- 7.Harmat L, Takacs J, Bodizs R: Music improves sleep quality in students. J Adv Nurs. 2008, 62 (3): 327-335. 10.1111/j.1365-2648.2008.04602.x.Article PubMed Google Scholar
- 8.Hughes JR, Daaboul Y, Fino JJ, Shaw GL: The “Mozart effect” on epileptiform activity. Clin Electroencephalogr. 1998, 29 (3): 109-119.CAS Article PubMed Google Scholar
- 9.Lin LC, Lee WT, Wu HC, Tsai CL, Wei RC, Jong YJ, Yang RC: Mozart K.448 and epileptiform discharges: effect of ratio of lower to higher harmonics. Epilepsy Res. 2010, 89 (2–3): 238-245.Article PubMed Google Scholar
- 10.Lin LC, Lee WT, Wang CH, Chen HL, Wu HC, Tsai CL, Wei RC, Mok HK, Weng CF, Lee MW: Mozart K.448 acts as a potential add-on therapy in children with refractory epilepsy. Epilepsy Behav. 2011, 20 (3): 490-493. 10.1016/j.yebeh.2010.12.044.Article PubMed Google Scholar
- 11.Ko TS, Holmes GL: EEG and clinical predictors of medically intractable childhood epilepsy. Clin Neurophysiol. 1999, 110 (7): 1245-1251. 10.1016/S1388-2457(99)00068-1.CAS Article PubMed Google Scholar
- 12.Shinnar S, Berg AT, Moshe SL, O’Dell C, Alemany M, Newstein D, Kang H, Goldensohn ES, Hauser WA: The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up. Pediatrics. 1996, 98 (2 Pt 1): 216-225.CAS PubMed Google Scholar
- 13.Arts WF, Geerts AT: When to start drug treatment for childhood epilepsy: the clinical-epidemiological evidence. Eur J Paediatr Neurol. 2009, 13 (2): 93-101. 10.1016/j.ejpn.2008.02.010.Article PubMed Google Scholar
- 14.Greenwood RS, Tennison MB: When to start and stop anticonvulsant therapy in children. Arch Neurol. 1999, 56 (9): 1073-1077. 10.1001/archneur.56.9.1073.CAS Article PubMed Google Scholar
- 15.Attanasio G, Cartocci G, Covelli E, Ambrosetti E, Martinelli V, Zaccone M, Ponzanetti A, Gueli N, Filipo R, Cacciafesta M: The Mozart effect in patients suffering from tinnitus. Acta Otolaryngol. 2012, 132 (11): 1172-1177. 10.3109/00016489.2012.684398.Article PubMed Google Scholar
- 16.Cacciafesta M, Ettorre E, Amici A, Cicconetti P, Martinelli V, Linguanti A, Baratta A, Verrusio W, Marigliano V: New frontiers of cognitive rehabilitation in geriatric age: the Mozart Effect (ME). Arch Gerontol Geriatr. 2010, 51 (3): e79-e82. 10.1016/j.archger.2010.01.001.CAS Article PubMed Google Scholar
- 17.Lubetzky R, Mimouni FB, Dollberg S, Reifen R, Ashbel G, Mandel D: Effect of music by Mozart on energy expenditure in growing preterm infants. Pediatrics. 2010, 125 (1): e24-e28. 10.1542/peds.2009-0990.Article PubMed Google Scholar
- 18.Lin LC, Lee MW, Wei RC, Mok HK, Wu HC, Tsai CL, Yang RC: Mozart k.545 mimics mozart k.448 in reducing epileptiform discharges in epileptic children. Evid Based Complement Alternat Med. 2012, 2012: 607517-PubMed PubMed Central Google Scholar
- 19.Scotoni AE, Manreza ML, Guerreiro MM: Recurrence after a first unprovoked cryptogenic/idiopathic seizure in children: a prospective study from Sao Paulo, Brazil. Epilepsia. 2004, 45 (2): 166-170. 10.1111/j.0013-9580.2004.16503.x.Article PubMed Google Scholar
- 20.Hart YM, Sander JW, Johnson AL, Shorvon SD: National General Practice Study of Epilepsy: recurrence after a first seizure. Lancet. 1990, 336 (8726): 1271-1274. 10.1016/0140-6736(90)92960-P.CAS Article PubMed Google Scholar
- 21.Lin LC, Lee WT, Wu HC, Tsai CL, Wei RC, Mok HK, Weng CF, Lee MW, Yang RC: The long-term effect of listening to Mozart K.448 decreases epileptiform discharges in children with epilepsy. Epilepsy Behav. 2011, 21 (4): 420-424. 10.1016/j.yebeh.2011.05.015.Article PubMed Google Scholar
- 22.Yuen AW, Sander JW: Can slow breathing exercises improve seizure control in people with refractory epilepsy? A hypothesis. Epilepsy Behav. 2010, 18 (4): 331-334. 10.1016/j.yebeh.2010.05.019.Article PubMed Google Scholar
- 23.Lotufo PA, Valiengo L, Bensenor IM, Brunoni AR: A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs. Epilepsia. 2012, 53 (2): 272-282. 10.1111/j.1528-1167.2011.03361.x.Article PubMed Google Scholar
- 24.Chuang CY, Han WR, Li PC, Young ST: Effects of music therapy on subjective sensations and heart rate variability in treated cancer survivors: a pilot study. Complement Ther Med. 2010, 18 (5): 224-226. 10.1016/j.ctim.2010.08.003.Article PubMed Google Scholar
- 25.Okada K, Kurita A, Takase B, Otsuka T, Kodani E, Kusama Y, Atarashi H, Mizuno K: Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia. Int Heart J. 2009, 50 (1): 95-110. 10.1536/ihj.50.95.CAS Article PubMed Google Scholar
- 26.Lin LC, Chiang CT, Lee MW, Mok HK, Yang YH, Wu HC, Tsai CL, Yang RC: Parasympathetic activation is involved in reducing epileptiform discharges when listening to Mozart music. Clin Neurophysiol. 2013, 124 (8): 1528-1535. 10.1016/j.clinph.2013.02.021.Article PubMed Google Scholar
- 27.Odano I, Varrone A, Savic I, Ciumas C, Karlsson P, Jucaite A, Halldin C, Farde L: Quantitative PET analyses of regional [(11)C]PE2I binding to the dopamine transporter – Application to juvenile myoclonic epilepsy. Neuroimage. 2012, 59 (4): 3582-3593. 10.1016/j.neuroimage.2011.10.067.CAS Article PubMed Google Scholar
- 28.Szyndler J, Maciejak P, Turzynska D, Sobolewska A, Bidzinski A, Plaznik A: Time course of changes in the concentrations of monoamines in the brain structures of pentylenetetrazole-kindled rats. J Neural Transm. 2010, 117 (6): 707-718. 10.1007/s00702-010-0414-7.Article PubMed Google Scholar
reference link: https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/1472-6882-14-17
More information: Here are links to excerpts from the Mozart piano sonatas mentioned in the article:
K448 for 2 pianos, (pianists Murray Perahia and Radu Lupu) open.spotify.com/embed/album/0 … fMutJIKcohWLEZ3UhAux
K545 sonata (pianist, Lang Lang) open.spotify.com/embed/album/2 … 6Cg49cL6PtyDODubUzGY
