Revista Argentina de Clínica Psicológica 2020, Vol. XXIX, N°2, 1493-1499
DOI: 10.24205/03276716.2020.393 1493
E
FFECT AND
M
ECHANISM OF
M
USIC
T
HERAPY ON
N
EURAL
R
ESTORATION IN
P
ATIENTS WITH
E
PILEPSY
Yue Su
Abstract
Epilepsy is a chronic disease of the nervous system that torments the body and mind of the patient. Despite the availability of some treatments, epileptic patients are still troubled by treatment effect, complications and high cost, to name but a few. This calls for effective and economical method for the treatment of epilepsy. This paper explores the effect of music therapy on the neural restoration of epilepsy and its neural mechanism. A total of sixty 6-week-old healthy male mice were randomly divided into epilepsy group, music group, white noise group, and healthy group. Status epilepticus (SE) was induced in the mice of the first three groups through pilocarpine injection. Mozart music was played to the music group for 3h a day, while white noise played to the white noise group. For the other two groups, no music or white noise was played. After 8 weeks, the effects of music therapy on epilepsy in mice were investigated by observing the frequency, duration, and intensity of epileptic seizure. The results show that the mice in the music group had fewer frequencies, less duration, and reduced intensity of epileptic seizures after several weeks of treatment than those in the other groups. This means music therapy has a relieving effect on epilepsy. The research is of great significance for the clinical treatment of epilepsy.
Key words: Music, Epilepsy, Electroencephalogram (EEG), Pilocarpine.
Received: 22-03-19 | Accepted: 11-08-19
INTRODUCTION
Epilepsy is a common neurological disease (Kwan & Brodie, 2000). It is a sudden abnormal discharge of neurons in the brain, resulting in transient brains dysfunction, which is characterized by repeated attacks. According to statistics, approximately 50 million people worldwide suffer from epilepsy (Wiebe, Rose, Derry et al., 1997), including more than 10 million children (Lin, Ouyang, Chiang et al., 2014). The causes of seizures are very complex. The mechanism of seizures has not been fully understood, and the frequency and duration of epileptic seizures are quite different. Epilepsy cannot be eradicated (Baskind & Birbeck, 2005). The main treatment currently is drug therapy
School of Music Chifeng University, Chifeng 024000, China. E-Mail: sy815503040@126.com
(Chen, Chow, & Lee, 2001), but 30% of patients cannot be controlled by drugs. It is called drug resistant epilepsy (Trevathan, 2000). Therefore, research on safe, economical and effective methods of treating epilepsy (Dua, De Boer, Prilipko et al., 2006) is of great significance to both patients and society.
Music therapy (Liao,Jiang, & Wang, 2015) has been widely used in the field of cognitive neuroscience. Many studies have found that music can enhance dendritic branching and neurogenesis in the hippocampus of the brain and contribute to the improvement of short-term intelligent quotient (IQ). Some studies have found that Mozart music (Lin, Lee, Wang et al., 2011) can improve the pathological conditions of Parkinson’s disease and senile dementia in different degrees (Pacchetti, Mancini, Aglieri et al., 2000). Some have even found that listening to Mozart K448 music significantly reduces the number of epileptic seizures (Lin,Lee, Wu et al.,
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2011), and some patients no longer have seizures after music therapy. About 80% of epilepsy originates from the temporal lobe lesions in the brain which is in the same area of the brain as the cortical layer that processes music. Therefore, for the treatment of epilepsy and prevention of seizures in patients, it’s of great significance to study the effect of the music on the brain of epilepsy patients (Tuft & Nakken, 2014).
At present, the effect of music therapy on epilepsy is only limited to the alleviation and improvement of Mozart’s music (Lin, Lee, Wu et al., 2010), but there has been little research on the neural mechanisms involved. Therefore, this paper applies a widely used drug resistant epilepsy model-pilocarpine epilepsy animal model, and in its period of onset, study the effect of music therapy on the repair of brain nerves and its neural mechanism in patients with epilepsy. This is of great significance that the therapy is for clinically promoting the music therapy to a wider range, to reduce the patient’s medical expenses and improve their quality of life.
EPILEPSY AND MUSIC THERAPY
Classification and treatment of epilepsy
Epilepsy is a long-term neurological disorder that is mainly caused by an imbalance of neurotransmitters in the brain. In epileptic seizures, the main manifestation is convulsions. Convulsions may occur anywhere in the body and even the whole body, and severe cases may be accompanied by brief periods of low consciousness or loss of consciousness. The classification of epilepsy in terms of its descriptive diagnosis is shown in Fig.1 below.
Figure 1
.
The classification of epilepsy
As a chronic brain disease that can occur in people of all ages, epilepsy has brought pain and trauma to the patient’s life for a long time. Therefore, effective and timely treatment of epilepsy is very important to improve the patient’s quality of life. At present, about 70% of epilepsy patients can control epileptic seizures through antiepileptic drugs, but long-term drug treatment will have negative impact on the patient’s mentality and personality. Besides, 30% of patients are drug-resistant, and they have to be treated by neurosurgery (Ficker, So, Mosewich et al., 1999) and neurostimulation therapy etc. The epilepsy lesions are in the brain, so the risk of surgery is very high and the cost is relatively high. Even so, there are still some patients with no effective way to control epilepsy. Therefore, it’s urgently required to explore and study a safer, more effective, and more economical treatment method.
Animal models of epilepsy
At present, the pathogenesis of epilepsy hasn’t been fully understood. Therefore, there still requires a lot of research. Many experiments and drug researches are mainly based on animal models. Fig.2 below lists several general standards for animal models that are eligible for the study of certain types of epileptic symptoms.
Figure 2
.
The standard of the animal model
Animal model is mainly used for the development of new antiepileptic drugs. The most commonly used models are:
1) Genetic model: The whole-body seizure epilepsy model is mainly used to understand the pathogenesis of epilepsy.
EFFECT AND MECHANISM OF MUSIC THERAPY ON NEURAL RESTORATION IN PATIENTS WITH EPILEPSY 1495
2) Electrically kindling model: A model simulating human temporal lobe epilepsy is made by electrically stimulating the amygdala and hippocampus of animals. Long-term stimulation can cause post-discharge and produce motorized epilepsy. The main feature is the ability to achieve accurate local stimulation of the brain and control the epileptic attack period.
3) Chemically kindling model: The state of epilepsy is produced by the injection of chemical reagents. Special attention should be paid to the control of the dose of chemical reagents. If the dose is too high, it will easily lead to death. In this paper, the drug resistant epilepsy model - pilocarpine-induced temporal lobe epilepsy animal model was adopted.
Mechanism of music on cerebral nerves repair in patients with epilepsy
Music can not only delight the mood but also has an important role in the improvement of many chronic diseases. At present, there are few cases of using music to treat epilepsy. Some studies have shown that after playing Mozart’s music to epilepsy patients, a large proportion of patients’ symptoms can be relieved. This may be related to the activation of cerebral cortex regions such as prefrontal lobe and temporal lobe etc. caused by Mozart K448 music. However, the current basis for the treatment of epilepsy in music is limited to Mozart’s music, while other music is not found to have this effect for the time being. Based on the research results, some neuroscientists proposed the following four hypotheses of music on the repair mechanism of brain nerve in epilepsy patients, as shown in Fig.3.
Figure 3
.
The hypothesis of music therapy to
epilepsy
MATERIALS AND METHODS
Experimental subjects and instruments
Sixty 6-week-old healthy male mice were randomly divided into epilepsy group, music group, white noise group, and healthy group. Mice were housed in individually ventilated cages for a week. Automatic lighting was switched on and off in the house to ensure light and dark cycles. Light was emitted from 6:00 to 18:00 and the ambient temperature was controlled at approximately 22 degrees Celsius.
The main instruments include rat stereotaxic apparatus, commutators, and EGG recording cranial electrodes, all purchased from American companies. Signal amplifiers, digital-to-analog converters were purchased in the United Kingdom.
Experimental methods
Embedded electrodes
After the mice were adapted to the feeding environment, the mice were first subjected to electrode implantation. The mice were anesthetized and placed on a stereotaxic apparatus for intracranial embedding of the EGG electrode. The position of the implanted electrode and the reference electrode was recorded, and the postoperative EEG recording was started one week after the recovery of the mouse.
Establishment of status epilepticus model In order to reduce the peripheral cholinergic effect, all mice were pre-treated with 1mg/kg scopolamine to prevent the mice from suffocating due to excessive respiratory secretions. 30 minutes later, intraperitoneal injection of pilocarpine at a dose of 30 mg/kg was made to mice in the music group, the epilepsy group, and the white noise group, while the healthy group was injected with an equal amount of physiological saline. After drug injection, it’s regarded as successful if the seizures reached Racine’s grade 3 or higher and the state lasted over 30 minutes. If no status epilepticus appeared one hour after the drug injection, 10 mg/kg of pilocarpine was injected once every 30 minutes; but if it’s still unsuccessful after three injections, the mice would be eliminated. For successfully epilepsy-induced mice, the 150 mg/kg chloral hydrate was administered to terminate the epileptic seizure
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after 30-minute status epilepticus, and healthy mice were injected with the same amount of physiological saline.
Table 1.
Racine’s classification
Level Behavioural performance
0 No Behaviour changes
1 Facial spasms, Slobber, Stare
2 Regular nod
3 Unilateral limb twitching
4 Standing limbs convulsions
5 Lose Balance control, appear to fall, violent jump or death
Music therapy experiment
After modelling the mouse’s epileptic state, mice were started with music therapy experiments. the Mozart grand piano sonata K.448 and the white noise by software synthesis group played to the mice in the music group and the white noise group respectively during the active period (18 o’clock to 21 o’clock) at night each day, and the sound intensity was 80dB. The other two groups of mice were treated with no noise. For music therapy, the EGG-video detection system recorded the EGG before, during, and after stimulation, the sampling rate was set to 1000Hz, and the filtering range was 1Hz to 50Hz.
Statistical analysis
SPSS16.0 software was used for statistical analysis. All data were expressed in mean ± S.E.M. One-way analysis of variance was used to compare the seizure frequency, seizure grade etc. between different groups. Sample T-test was applied for the comparison between the music group, epilepsy group, and healthy group; P<0.05 is statistically significant.
RESULTS AND DISCUSSIONS
Establishment of epilepsy model
Fig.4 shows the survival rate of each group and the success rate of epilepsy state, in which group 1 to group 4 are music group, white noise group, epilepsy group and healthy group respectively. The death of all groups of mice occurred in the incubation period, where the mortality rate of healthy mice was 0%. Undead mice started to suffer from repetitive spontaneous attacks after a two-week incubation period.
Figure 4
.
The survival and success rate of
mouse model
Influence of music on epilepsy
The influence of music on epilepsy can be judged by the frequency, duration, and intensity of epileptic seizures. In this section, the mice at the third and sixth weeks of music therapy were compared to see how music therapy can improve epileptic seizures.
Music therapy and epileptic seizures frequency
The frequency of epileptic seizures is an important measure of the severity of epilepsy. Fig.5 is the comparison of seizures frequencies between the third and sixth week of music therapy. In the third week of music therapy, there was no difference in the frequency of epileptic seizures in each group. But by the sixth week, epileptic seizure frequency in the music group was significantly reduced, while there was no significant difference between the white noise group and the epilepsy group. To further clarify when music therapy works best, the epileptic seizure frequency during and after music play was compared, as shown in 3, 4, 5 and 6 of Fig.5, respectively. By comparison, it’s found that during the music play, the frequency of seizures in the music group decreased, even more significantly in the sixth week; during the music stop, there was basically no difference with the seizure frequency between the music group and the epilepsy group or white noise groups, indicating that music can reduce the frequency of seizures mainly during the playing of music. In addition, the frequency of seizures in the white noise group during the entire experiment basically remains the same, indicating that white noise has little effect on reducing the frequency of seizures.
EFFECT AND MECHANISM OF MUSIC THERAPY ON NEURAL RESTORATION IN PATIENTS WITH EPILEPSY 1497
Figure 5
.
Effects of music on the frequency
of seizures
Music therapy and epileptic seizure duration
Figure 6
.
Effects of music on the duration of
seizures
The status epilepticus is the frequent recurrence under incomplete recovery of consciousness between continuous attacks of epilepsy or the duration for more than 30 minutes. The duration of epileptic seizures has a major impact on the patient’s life. The status epilepticus can cause hyperthermia, circulatory failure, or excitotoxic damage to neurons that leads to irreversible brain damage, high morbidity or mortality rate. Therefore, the effectiveness of music therapy on epilepsy can be evaluated by shortening the duration of status epilepticus. Fig.6 is the comparison of epileptic duration between the third and sixth weeks of musical therapy. In the third week, the duration of epilepsy in the music group had tendency to decrease during the music play, but there was no significant difference from other groups when the music was stopped; however, at the sixth week, it’s found that the duration of
epilepsy in the music group was significantly shortened both during the playing of the music and when the playing time was stopped, indicating that with the accumulation of music therapy time, the music has a long-term effect on shortening the duration of seizures.
Music therapy and epileptic seizure intensity
Figure 7
.
Effects of music on the grade of
seizures
(a)
(b) During the music play
(c)During the music stop
In addition to the duration of seizures, the grade of seizures is another important indicator for measuring the severity of epilepsy. The effectiveness of music therapy on epilepsy was evaluated by studying changes in the grade of seizures before and after music therapy. Since
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seizure grades 1 and 2 are difficult to distinguish, only grades 3-5 epilepsy were used for comparison in Fig.7. From Fig.7(a), it was found that the percentage of high-grade seizures in the music group decreased during the third and sixth weeks, while there was no significant difference in other grades. In order to further determine the timing of music therapy, statistics were made on the seizure grade during the music play and during music stop, respectively, as shown in Fig.7(b) and (c). During the music play, there was a significant reduction in seizures at grade 5 in the music group, but at the third week, the grade-4 seizures in the music group were significantly higher than in the other groups. During the music stop, at the third week, there was no significant difference in the seizure grades for the three groups. By the sixth week, the proportion of seizures in the music group at grade 3 increased. The above results show that music has the effect of reducing epileptic seizures, and as the treatment time increases, the effect can be extended to the music-stop period.
Discussions
Music is a part of people’s life. Music can not only enrich life, regulate emotions, but also have many positive effects on the brain function. Many studies have shown that music has therapeutic and improvement effects on many diseases of the nervous system, such as Alzheimer’s disease, stroke, etc. The “Mozart effect” is sourced from the discovery that listening to Mozart music can significantly improve the spatial reasoning ability of testers in a short time, and then it attempts to apply Mozart music to the alleviation and treatment of more diseases.
The above experimental results show that the most important effect of music on epilepsy therapy is produced during music play. Music may play a role in relieving and treating epilepsy by means of neurotransmitters adjustments such as trigeminal stimulation and vagal stimulation etc. Studies have found that music can increase the release of peptides in the brain, and that dopamine can not only delight the feelings, but also can treat epilepsy and protect nerves. Increased dopamine reduces the frequency of seizures by increasing the threshold for seizures and shortens the duration of seizures.
The experimental results show that the effect
of music on the frequency of epilepsy is reflected when it decreased at the third weekend and didn’t appear until the sixth week, because music may change the neural networks in the cortex and subcortical areas to form new pathways in the brain. This will help reduce the incidence of epilepsy, and the formation of new pathways takes time
CONCLUSIONS
In this study, epilepsy was induced by pilocarpine mouse model. This model has high similarity with human temporal lobe epilepsy in terms of pathology, EEG and behaviour, which is of important reference value for human clinical practice. Through experiments, the following conclusions have been made:
(1) Mozart’s music has an improved effect on epilepsy in pilocarpine model mice. During the period of music therapy, especially during the time of music play, the frequency of epileptic seizures in mice was significantly reduced, seizures duration was significantly shortened, and the grade of seizures was also significantly decreased. With the extension of music treatment time, the effect of music therapy tends to work during the music stop. It is a safe and effective method to treat epilepsy.
(2) Studies have shown that music helps to increase the approximate entropy of EEG during seizures, thereby increasing the threshold of seizures. The reason that music therapy is effective for epilepsy may be related to the fact that the whole brain neuronal wave is suppressed by music-enhanced GABA.
Acknowledgements
Scientific research project of institutions of higher learning of the department of education of Inner Mongolia autonomous region in 2018.
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