Neurophysiological aspects of musical auditory stimulation on the cardiovascular system

introduction: The literature has shown that musical stimulation can influence the cardiovascular system, however, the neurophysiological aspects of this influence are not yet fully elucidated. Objective: This study describes the influence of music on the neurophysiological mechanisms in the human body, specifically the variable blood pressure, as well as the neural mechanisms of music processing. Methods: Searches were conducted in Medline, PEDro, Lilacs and SciELO using the intersection of the keyword “music” with the keyword descriptors “blood pressure” and “neurophysiology”. results: There were selected 11 articles, which indicated that music interferes in some aspects of physiological variables. conclusion: Studies have indicated that music interferes on the control of blood pressure, heart and respiratory rate, through possible involvement of limbic brain areas which modulate hypothalamic-pituitary functions. Further studies are needed in order to identify the mechanisms by which this influence occurs.

Ferreira LL, Vanderlei LCM, Abreu LC, Guida HL, Valenti VE iNtrODUctiON Currently, music has been used as a therapeutic agent to facilitate, promote and contribute to a better quality of life (QoL) of patients in various specialties -and for that, called music therapy 1,2 -and it has also been the subject of studies linking their use adjunct to other therapies [3][4][5][6][7][8][9] .This therapy involves the skillful use of musical elements in order to improve the physical and mental health of a person, as a way of providing emotional and spiritual support, and in order to reduce stress levels and anxiety 1,2 .
In this context, some authors point out that music can cause different physiological responses, such as changes in blood pressure, heart and respiratory rate, body temperature, galvanic skin responses, biochemical parameters and endocrine emotional changes 10,11 .
In recent years, literature has investigated the relationship between musical stimuli and the cardiovascular system 12 , and has increased the experimental evidence which shows that some types of music can influence cardiac and neurological functions and biochemical reactions, and that it can trigger measurable reduced effects related to stress 13 .
Another source of interest for scientific studies is to explain the neurological level on how the different components of emotional processing of music causally interact.One explanation says that, known for perceiving emotional stimuli (music or other sound), there is an increased activity of the sympathetic nervous system and the somatic nervous system 14 .
Based on the foregoing it is possible to understand the importance of using music as a therapeutic alternative for treatment overall, improving mental health through physiological changes, and based on the absence of original scientific review to identify the role in the musical stimulus neural pathways of the human body, justifying the need for this study.Thus, the objective of this study was to characterize the influence of music on the neurophysiological mechanisms of the human body, specifically the variable blood pressure, as well as identifying the neural mechanisms of processing music.

Selection and characteristics of studies
It was a literature review with the application of a search strategy to select articles from queries to databases Medline (via PubMed), PEDro, Lilacs and SciELO, with articles published between January of 2000 and December of 2012.Were used to search the intersection of "music" keyword descriptors such as "blood pressure" and "neurophysiology" through the boolean operator "and", which were defined based on the Health Sciences Descriptors (HSD) and its corresponding English language Medical Subject Headings (MeSH).

criteria for inclusion and exclusion
We included epidemiological (case series, cross-sectional, case-control or cohort) or experimental studies, published in English, Portuguese or Spanish, available in full, with information which contemplated theme songs and blood pressure, and humans as experimental subject.
Articles that did not contemplate the inclusion criteria, articles published in non-indexed journals, articles that had values less than five in the analysis of methodological quality PEDro, and texts of academic dissertations or theses were excluded.
The full texts of the articles included in the study were evaluated, and their reference lists were checked independently, to identify potential items that could be included in this work, but were not previously found in the electronic search.

Selection strategy
For the selection of articles, it was initially performed valuing the securities related to the topic in question.This selection was based on the titles, as they approached the main idea of applying some musical stimulation in humans, as well as their influence on the cardiovascular and/or neurological systems, and titles that had the word music or some information concerning this word as a musical style.At the end of the search, we excluded repeated titles, since it was held in various databases.Then detailed summaries of selected articles were read in order to select those that exclusively addressed the topic proposed for this review.With the exception of abstracts that did not address the issue at hand, the full texts were evaluated, and those who fulfilled the inclusion criteria were included as the final result of the search.

Data analysis
The data were analyzed qualitatively and presented in tabular form with a description of the following: author and year of study, objectives of the study, general characteristics of the population, results and score on the PEDro scale.
The studies analyzed their methodological quality using the PEDro scale.The scale has 11 questions, in which only ten are scored.Thus, the score ranges from zero to ten.Each criterion is scored according to its presence or absence in the study assessed.Each satisfied item (except the first) contributes on one point to the total score.The items not described in the studies are classified as "not reported" and they are not scored.The final score is obtained by summing all the positive responses 15 .The studies indexed in the PEDro database already had methodological quality assessment.The studies not indexed in the PEDro were evaluated independently.
In a systematic review of studies, to be classified as "high quality", the study must have a score greater than 50% regarding its maximum possible score 15 .Thus, for the present review, all studies with scores greater than or equal to five points, were considered studies of high methodological quality.

Musical stimulation and cardiovascular system reSUltS
We found 61 articles in the electronic search in the databases.Selected these, 43 of them were excluded after applying the inclusion and exclusion criteria proposed.Besides these, seven articles were also excluded for not having sufficient methodological quality, according to the PEDro scale.Thus, as a result, 11 articles were selected for this review, which are summarized in Table 1.
We found only two papers 11,16 which investigate directly the music and its effects on blood pressure, demonstrating a lack of studies related to the topic.Moreover, in five studies 10,[17][18][19][20] , we found no statistically significant difference (p<0.05) on changes in blood pressure.Among the 11 studies that comprised the present study, only 45.5% observed reduction of variable blood pressure under influence of music.
Other related parameters such as oxygen saturation (SpO 2 ), heart rate (HR) and respiratory rate (RR) were, respectively, 50, 57.1 and 100% reduced among those studies that assessed these variables.Other variables such as QOL in individuals with hypertension 11 , pain relief in cancer patients 17,21 , reduced anxiety 19 and factors such as levels of anesthetics in surgical patients 10,19,20,22 , post-traumatic stress associated with musical stimulation 16 , induced coma situations 23 and influence of music on musicians and no musicians 24 were also targets of selected articles in this review.
The studies analyzed investigated responses to different musical styles, namely, slow classical music, fast classical music, twelvetone music, Techno, rap and raggae music, in individuals of both sexes, with ages ranging from one day of birth, past children aged four to 16 years, young graduates, to 65-year-old seniors.
Finally, the average score obtained, by applying the PEDro scale, was 6.73±1.01 points, meaning it can be stated that the articles showed highly acceptable methodological quality, though not outstanding, since the maximum score is 10 points.

DiScUSSiON
In general, the analysis of texts selected for this review suggests that music can have a real role in the regulation of blood pressure through its neural processing.This modulation occurs, largely, by the activity of the autonomic nervous system, as well as its branches, the sympathetic and parasympathetic nervous system, acting directly on the cardiovascular system components.
Anatomically, the primary acoustic circuit in humans consists of the auditory nerve, brain, thalamus (medial geniculate body) and auditory cortex.The sound stimulus is picked up by the outer ear that conducts sound energy by the canal toward the eardrum.This membrane transmits vibrations to the ossicles in the middle ear (hammer, anvil and stirrup), generating mechanical energy 25 .
The auditory nerve makes synapses with neurons in the cochlear nucleus until the action potential reaches the brain.In the cochlear nucleus, the action potential goes to the medial geniculate body (auditory thalamus) and then follows up to the auditory cortex 25 .This is located in the transverse spin, Helsh, the lateral fissure.
The auditory cortex performs a perceptive analysis of the music, extracting specific information about their acoustic characteristics, such as pitch, timbre, intensity and roughness 26 .
The musical functions are complex, multiple and asymmetric, involving the right hemisphere for pitch, timbre and melodic discrimination and the left hemisphere for rhythms, melody semantic identification, sense of familiarity, sequential and temporal processing of sounds 27 .
Faced with a musical stimulus, individuals create positive or negative expectations based on their cultural, emotional, social and environmental interactions.Thus, if music meets positive expectations, subjects relax, however, if the same matches in a negative way, the person may be under tension.Thus, through the succession of expectations met or frustrated with their relaxation or tension results, it is formed the basis of the neurophysiological responses to music, raising or normalizing blood pressure 28 .
By stimulating the brain, the limbic system of sound will act, more specifically, in the amygdaloid complex, a region involved in processing emotions.This complex, in a situation of stress, fear or sadness, stimulates the hypothalamic neurons, and consequently stimulates the anterior pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream, reaching the adrenal glands, which then releases the cortisol hormone, known as the stress hormone 21 .
The autonomic nervous system (ANS) is another neural component that has direct relation with the neurophysiological responses to musical stimuli 29 .It is divided into the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS), and provides innervation to all body organs, glands, smooth muscle and cardiac muscle.The SNS prepares the body for fight or flight, through physiological changes in blood pressure, heart rate and breathing 30 .
Modulation of sympathetic and parasympathetic nervous system is involved in at least three reflex arcs, namely: 1) reflex arcs involving the arterial baroreceptors (receptors present on the system of high blood pressure -high circulation); 2) reflex pathways related to cardiopulmonary receptors (low system pressure -small circulation); and 3) reflex arcs related to arterial chemoreceptors (central and peripheral) 30,31 .These reflex responses of the sympathetic and parasympathetic allow adjustment of cardiac output and peripheral vascular resistance, contributing to the stabilization and maintenance of systemic blood pressure during different physiological situations 30,31 .
The parasympathetic, or vagal activity, exerts inhibitory effects or depressants, translated by bradycardia due to sinus node inhibition, depression of atrioventricular conduction, depression of excitability of specialized conductive fibers and myocardial inotropism and depression.These effects contributed to the relative electrophysiological heart balance, becoming then antiarrhythmogenic factors and providing a stabilization of blood pressure 32 .
Cardiovascular responses to sound can be triggered by many ways, and one example is the startle response, mediated by a brainstem circuit.The acoustic startle, a well-known effect of loud sounds on the cardiovascular system, is described as the sudden heart rate and blood pressure response to an excessively high sound stimulation.A typical intensity, used to elicit a startle reflex, is 110 dB, being this a much higher intensity than the ambient noise.However, the responses to cardiac acceleration, commonly used in clinical trials, observed that some individuals have been exposed to stimuli at 60 and 110 dB noise.The increase in blood pressure and heart rate, in response to acoustic startle stimuli, indicates an autonomic function to respond to acoustic stimuli 29 .
It is believed that there is a correlation between the operation of the SNS, the emotions and hypertension, since brain areas related to emotional behavior, they occupy very wide territories on the telencephalon and diencephalon, in which structures that are part of the limbic system, such as the prefrontal area and hypothalamus, through the ANS, regulate the visceral activities 32 .
The mechanism of blood pressure regulation composes complex physiological functions, depending on the system of integrated cardiovascular, renal, neural and endocrine systems.This regulation is the result of the activity of feedback systems, which operate in short and long terms.The main control mechanism in the short term is played by reflexes that are originated in the arterial baroreceptors, and stretch receptors into the cardiopulmonary region 30,31 .
Factors related to the ANS may be influenced by the music, making it a modulator of this system, influencing blood pressure.When music meets the expectations of the subject, they are able to relax through the ANS balance between sympathetic and parasympathetic.When the music does not meet expectations, the subject can get tense due to the SNS and reverse the action of PNS 28 .
Another factor that could explain the blood pressure regulation through music is the decreased release of catecholamine (adrenaline and noradrenaline), inducing vasodilation, among other factors, which consequently result in a decrease in blood pressure 16,25 .
In summary, the studies selected for this review have shown that musical stimulation produces cardiovascular changes, induced by central physiological mechanisms, which are dose-dependent factors, such as musical style, the physical condition of the subject, and the time and intensity of exposure.Such findings are important for health professionals, since music can be used as an adjunct in the treatment of various diseases and disorders, becoming thus the appropriate knowledge of their effects on the human body, for a proper prescription.In this context, the music therapist is a professional who can contribute to the health teams, training it, in order to act in different contexts and in different clinical hospital situations.
In conclusion, the results suggest that music can regulate blood pressure levels through its neural processing, by decreasing sympathetic activity, associated with an increase in vagal activity, producing bradycardia, decreasing total peripheral resistance and cardiac output, and contributing to maintaining blood pressure at normal levels.