[PookztA]

I've wanted to share this study I am organizing for a while but thought it would be best to keep it secret until I was further along with it. now that the study has passed numerous checkpoints of approval and secured funding from the Illinois Neurological Institute, I think it is an appropriate time to share it with the community. the next major step is subject recruitment which will be taking place soon after we clear the low-risk nature of the study with the local IRB (for subject protection purposes). please excuse the raw appearance of the text below, copying-pasting from Word does not always work that well.

Investigating the effects of music on alpha and theta wave activity in the human cerebral cortex: a pilot study

Investigator
Abraham Hafiz Rodriguez (M3)

Mentor
Dr. Sarah Nath-Zallek (Neurology)

Collaborators
Dr. Michael Xu (Neurology)
Dr. Lori Russel-Chapin (Neurology)
Dr. Julian Lin (Neurosurgery)
Dr. Jacqueline Henderson (Music Therapy)

University of Illinois College of Medicine – Peoria
James Scholar Research Proposal
Revised on July 5th, 2011

Table of Contents

ABSTRACT 1
BUDGET 2
ROLE OF STUDENT 2
OBJECTIVES OF STUDY 4
STUDY BACKGROUND AND SIGNIFICANCE 5
STUDY METHODS 8
REFERENCES 16
APPENDIX 17

ABSTRACT
Therapeutic properties of music have been suspected and discussed for many years, and despite the lack of extensive scientific research on the topic, music has been used by many to alleviate stress, anxiety, and even pain. Only in the last thirty or forty years have well-controlled clinical music therapy studies finally began to increase in frequency to shed more light on this important clinical topic. The following research proposal is for an electroencephalographic study that is aimed at shedding light on the neurological link between music, consciousness, and the physiological therapeutic benefits that have been elucidated by music therapy research over the last few decades. Modern research has shown human alpha (8-12Hz) and theta (4-8Hz) waves to be most prevalent during therapeutic mental states of deep relaxation and meditation periods (University Hospitals Of Cleveland, 2011). Our study will recruit 20-30 healthy, right-handed young adult subjects, to examine the effects of five unique musical genres on human cerebral cortex activity. Each subject will be exposed to one complete song from each of the following musical genres: Classical (Mozart), Tribal (African) Drumming, Goa Trance, Psytrance, and one Song of the Subject”s Choice.  There will be control periods of white noise both before and after the music therapy session, and control periods of white noise between songs during the session. EEG data-gathering will be primarily conducted by EEG technologists at the Illinois Neurological Institute OSF Sleep Center, with the oversight of Dr. Sarah Nath Zallek and Dr. Michael Xu. Our analyses will primarily focus on alpha and theta waves changes, but we will be taking EEG measurements of a wide range of frequencies all over the cortex.  We expect to see statistically significant elevations in the alpha-theta frequency range wave amplitudes and/or durations during periods of music therapy in comparison to control periods. Analysis of the EEG data will be done by Dr. Xu. The study will be overseen by Dr. Nath Zallek and Dr. Xu.

BUDGET
Equipment and Materials:  Computer, Music, Headphones, Electroencephalograph, Analysis Software (Music will cost approximately $20, other costs mentioned below).
Travel Costs:  Approximately $20 for each subject to reimburse travel and time costs.
Other:  EEG equipment rental and technician time will be paid for by the Illinois Neurological Institute. EEG analysis will primarily be done by the generous Dr. Xu for no charge.

ROLE OF STUDENT
Development of Project and Study Design
IRB Application and Process
Subject Recruitment and Obtaining Informed Consent
Administering Music Therapy and Collecting Data
Analysis, Manuscript, and Presentation Preparation

 
OBJECTIVES OF STUDY
• Primary Objective
o Determine if the five selected genres of music will cause statistically significant changes in the amplitude and/or duration of the combined alpha-theta frequency range (4-12Hz) in the human cerebral cortex of healthy young adults.
• Secondary Objectives
o Determine which genres of music showed the greatest, least, or no EEG changes.
o Determine which cortical regions showed the greatest, least, or no EEG changes.
o Determine which other cortical frequencies, if any, showed EEG changes.
o Discuss EEG differences in relation to the additional exploratory variables using the subject”s questionnaire results.

 
BACKGROUND & SIGNIFICANCE
Music has been suspected of having therapeutic properties for thousands of years, and ancient reports of musical therapy can be found in historic writings from ancient civilizations including Egypt, China, India, Greece, and Rome (University Hospitals Of Cleveland, 2011). The first modern uses of professional musical therapy in the United States date back to World Wars I and II, when music was used to relieve pain and agitation in soldiers with traumatic war injuries (University Hospitals Of Cleveland, 2011).  An example of modern research that has explored music”s clinical applications is a study conducted by P. Kliempt (Kliempt, Ruta, Ogston, Landeck, & Martay, 1999), which found that intra-operative ‘HemiSync” music therapy could reduce patients” requirements of Fentanyl during surgery. Another modern example of research showing use of music”s therapeutic properties in a clinical setting can be seen in a study conducted by Zare (Zare, Ebrahimi, & Birashk, 2010), which found that music therapy significantly reduced agitation and anxiety in patients with Alzheimer”s Disease.
Despite the increasing use of music for its anti-anxiety and anti-nociceptive properties, modern science still does not fully understand the physiological electrochemical sensory-response signal pathways behind the reported therapeutic properties of music. One example of research which has attempted to shed light on these biochemical pathways in addition to further exploring the therapeutic benefits of music, was a study done by Dr. Claudius Conrad in 2007 (Conrad, Niess, Jauch, Bruns, Hartl, & Welker, 2007). The study measured and compared vital signs and serum levels of various biochemical stress markers in a group of recovering post-operative patients who were exposed to daily music therapy and a group who were not exposed to music therapy.  The study found that patients who listened to 1-hour of classical music each day during recovery had statistically significant reductions in the biochemical stress markers cortisol, dehydroepiandrosterone, epinephrine, and IL-6. The study also found that music therapy lowered patients” blood pressures and Propofol requirements, while increasing serum levels of growth hormones in comparison to control subjects. These findings provide evidence which sheds light on one of the neurochemical pathways in which music may be producing its physiological therapeutic effects in the human body.
Based on current scientific literature, it seems both possible and likely that our proposed research efforts will further elucidate the neurological link between the conscious sensations and physiological therapeutic benefits that are produced by music. Using carefully selected controls and songs similar in composition to those used in previous studies, our proposed research efforts are likely to help shed important light on the neuroanatomical correlates and/or origins of the therapeutic electrochemical signals that are generated in the human central nervous system as a result of listening to particular genres of music.
Research examining music”s effects on human cerebral cortical activity has been ongoing for quite some time and is increasing in frequency, although very little research has specifically focused on elucidating the neural pathways triggered by music which may be generating the physiological therapeutic benefits seen in human music therapy studies. In one such EEG study by Koelsch (Kolesch, Maess, Grossmann, & Friederici, 2003), the research team examined differences in cerebral cortical activity between genders in response to various Neapolitan chord and music clusters. Another music-electroencephalography study, by Jacobs  (Jacobs & Friedman, 2004), compared the cerebral cortex activity of subjects listening to relaxing music to the cerebral cortex activity of subjects engaging in relaxation techniques. The study found that relaxation techniques increased theta wave activity even more than music did, and that alpha wave activity was insignificant and less reliable than theta wave activity.  A similar study by Baumgartner (Baumgartner, Esslen, & Jancke, 2006) revealed increases in alpha and theta wave activity in both frontal and posterior aspects of the human cerebral cortex in response to classical music, and a study by Yaun-Pin Lin (Lin, Duann, Chen, & Jung, 2010) also showed theta wave increases in response to classical music. A similar study by Kabuto (Kabuto, Kageyama, & Nitta, 1993) showed that relaxing music induced increases in theta and alpha wave activity in the human cerebral cortex, particularly in the occipital lobe. Another relevant study, completed just recently by Salimpoor (Salimpoor, Benovoy, Larcher, Dagher, & Zatorre, 2011), used fMRI and PET imaging scans to determine that pleasurable music caused endogenous dopamine release in the human striatum. This evidence suggests that music affects the well-known biochemical ‘pleasure” pathway of the central nervous system”s basal ganglia.
Our research team would like to take this opportunity to expand upon what is known about the neurological link between music”s effects on consciousness and music”s physiological therapeutic benefits. This field is new and important, especially considering that music is already being used in some clinical settings to improve patient care. The sooner we understand the effects of music on the human brain and body, the sooner we can apply the therapeutic healing powers that are contained within various musical frequencies and rhythms, such as those created by our ancestors for thousands of years.

STUDY METHODS
• Study Design
o Our proposed study will analyze changes in human cerebral cortex activity using electroencephalography, with a focus on alpha-theta frequency range wave amplitudes and durations, before, during, and after subjects listen to a randomized sequence of five unique songs that are suspected to have physiological therapeutic properties.
o Musical tracks which exceed 3 minutes in length will be cropped / edited to produce 3-minute clips that will serve as representations of the entire song from that genre, standardizing the song and control period lengths to ~3 minutes.
o We hypothesize that all five music genres will generate statistically significant changes in the durations and/or amplitudes of alpha-theta frequency range activity.
o All five selected music genres were chosen for particular reasons:
1. Classical (Mozart) was selected because of its successful use in other studies, such as Dr. Conrad”s (Conrad, Niess, Jauch, Bruns, Hartl, & Welker, 2007).
2. Tribal (African) Drumming was selected because of its cultural and historical relevance to our ancestral past, and also because of reports that fast-paced drumming rhythms have therapeutic trance-inducing properties.
3. Psychedelic Trance (Psytrance) was selected because of its reported therapeutic properties and its unique alpha wave-like composition.
• Psytrance is constructed using a bass-line of sixteen equally spaced beats per measure, in contrast to most other genres of electronic dance music which consist of only four beats per measure. This sixteen-beat Psytrance bass-line is produced at a speed of approximately 140-150 beats-per-minute, which results in most Psytrance songs having a frequency that is nearly identical to that of the alpha wave frequency (8-12Hz) seen in human cerebral cortex activity. The unique sixteen-beat bass-line of Psytrance is thought to entrain / increase the cortical alpha wave activity of the listener.
4. Goa Trance was selected because of its reported therapeutic properties and its drastic similarity to Psytrance. Goa Trance was created in Goa, India in the 1970s; it is the original form of Psytrance and is still being composed all over the world today. The one major difference between Goa Trance and Psytrance is that Goa Trance lacks the special sixteen-beat Psytrance bass-line, although they are still made using similar tempo, melodies, rhythm.
5. Song of Subject”s Choice was selected to investigate the importance of the subject”s music preference in determining how effective the therapy is.
• Subject”s song of choice must be available in instrumental form in order to prevent any potential complications from vocal stimuli.
o As this is a pilot study with limited resources and time, we only plan to recruit a sample of 20-30 young adult participants from local academic campuses.
o The subjects will be asked to participate in the therapy at the same time of day (most likely in the afternoon), regardless of which day they choose to participate.
 This will help control for the subjects” level of alertness and drowsiness.
• Subjects
o Our proposed study plans to recruit 20-30 healthy, right-handed subjects with normal hearing, between the ages of 18 and 28, from Bradley University, UICOMP medical school, and Illinois Central College.
o Subjects will be asked of any previous music training before the music therapy.
o Subjects will be required to avoid caffeine, tobacco, alcohol, and all other avoidable drugs and psychoactive chemicals for >5 hours before participating in the study.
o Dr. John Engdahl and Dr. Jacqueline Henderson from Bradley University have kindly pledged to assist with subject recruitment at their campus.
o Theoretical Risks and Potential Benefits:
• Minimal-risk study. Mild headache can result if patient truly finds a particular music genre to be irritating. Mild skin irritation can result from EEG electrode preparation and/or application. All EEG equipment used will be electrically grounded and of the quality and condition required for use with patients.
• Subjects may experience a direct emotional benefit during the music therapy session and/or an indirect emotional benefit after contributing to the planet”s current understanding of music”s therapeutic properties.
• Subjects may withdrawal from the study at any time if he/she chooses.
• Procedure
o Subjects will be briefed on the study”s risks and benefits, subjects will be informed that they can withdrawal from the study at any time, and informed consent will be obtained, before the music therapy begins.
o Subjects will wear closed-ear headphones while blind-folded and hooked up to an electroencephalogram. Each participant will then be subjected to one music therapy session consisting of a permutation-determined randomized sequence of five musical tracks, each approximately 3 minutes in length (one song from each of the following genres: Classical (Mozart), Tribal Drumming (130-150bppm), Psytrance (140-150bpm), Goa Trance (130-150bpm), and a Song of Subject”s Choice (must be Instrumental versions; i.e. no vocals), with 1-minute intervals of white noise (control) between each song). There will also be a 3-minute interval of white noise (control) at the beginning and end of each subject”s music therapy sequence.
o Subjects will be given this brief questionnaire before music therapy session:
• What is your Name? What is your Age? What is your Gender? What is your Ethnicity?
• Have you ever had any type of musical training, e.g. have you ever composed or produced music, played a musical instrument, or had singing lessons?
• If so, what music training do you have and how much?
• What are your three most favorite genres of music (any)?
• What are your three least favorite genres of music (any)?
• Have you heard songs from any of this study”s music genres before?
• If so, how many times have you heard a song from each genre?
• If so, how do you feel about the genres (i.e. like, dislike, neutral)?
• How much sleep did you get last night?
• How tired do you feel on a scale of 1-10 (1 = very alert; 10 = extremely tired)?
o Subjects will rate each song immediately after hearing it using a verbal equivalent of a Visual Analog Scale (VAS) scale (see Appendix).
 Immediately after each song ends during a subject”s music sequence, the investigator (Abraham) will gently tap the subject to prompt them to verbally rate the preceding song on a 1-10 scale (to one decimal place only).
 The subject will not remove their blindfold during this rating process.
 The subject will not be told the genre of the songs they are rating.
o Subjects will be given this brief questionnaire after the music therapy session:
• Now that you have heard all five music genres, will you please rank the songs you heard in order of how much you liked them?
• List the songs in order of how much you liked them, starting with the song you liked most in the #1 position at the top, and finishing with the song you liked least in the #5 position at the bottom.
• Do you have any questions for us? Please feel free to leave any comments, feedback, or requests you have for the researchers in the space below.
• Thank you for your help and contribution to the scientific community!
o Timeline of Study:
• 1.5-2 hours of data collection per subject; 20-30 subjects
• 30-60 hours of data collection time required total
• Time is also required for data analysis, review, and publication.
• Using 2-3 days per week of M3 year to conduct 2-4 data-recording sessions per week; approximately 20-40 weeks of data collection.
• Remainder of M3 year should provide adequate time for study completion.
• Measurement
o Measure combined alpha-theta frequency range wave amplitude (microvolts) and duration (seconds) during music therapy in all 4 lobes of subjects” cerebral cortex.
o Measure combined alpha-theta frequency range wave amplitude (microvolts) and duration (seconds) during control periods (white noise) in all 4 lobes of subjects” cerebral cortex.
o Measure amplitudes (microvolts) and durations (seconds) of other cortical frequencies in all 4 lobes of subjects” cerebral cortex from both periods for comparison.
o Duration will be calculated for each song separately, by determining the relative percentage of each song clip during which significant cortical activity was observed.
o Quantify the results from questionnaires into measurement data for analysis.
o EEG data will be obtained using the Nihon Kohden Neurofax EEG-1200A electroencephalograph and NK Neurofax QP 112AK v06-80 software (see Appendix).
o 19 EEG electrodes will be placed via the standard international 10-20 system.
• Analysis
o EEG data will be imported into Novatech WinEEG v2.7+ software for analysis.
o Data will be entered into an Excel sheet and then analyzed using SPSS (latest version). Descriptive statistics will be reported as mean, standard deviation, range and correlations. To test differences, repeated measures General Linear Models will be computed.  A significance level of p=<0.05 is accepted.
o Primary objective – To determine if the five genres of music will cause significant changes from baseline in the amplitude and/or duration of the combined alpha-theta frequency range (4-12Hz) activity in the human cerebral cortex of young adult subjects.
• separate repeated measures General Linear Model (GLM) each of the four outcome measures
• Predictor Baseline, Classical, Tribal Drumming, Psytrance, Goa, Subject choice
• Outcome amplitude alpha-theta, duration alpha-theta — if baseline does not change during sessions.
• Outcome base – adjacent song difference (base-difference) score for each of 4 outcomes should baseline vary between sessions.
o Secondary objective – Determine which areas of cortex showed the greatest, least or no changes.
• General Linear Model (GLM) repeated
• Predictor least favorite, most favorite
• Outcome compute average (or average change) over all genres as the dependent variable for each of the four measures duration alpha-theta, amplitude alpha-theta.
o Analysis of data will be done by Dr. Xu with Dr. Russel-Chapin”s WinEEG software
 The WinEEG software contains an extensive array of analysis commands and functions that will be helpful with this study, including but not limited to, EEG statistical analysis functions, EEG cortex mapping, EEG data comparison via automatic table and graph creation, manual analysis, and much, much more
 Dr. Xu reviewed the WinEEG user manual with me today and he said this software will work great for this study, and that it has so many features that it will work very nicely in presenting the data as well as analyzing it.
• We also confirmed that the EEG data file formats that are available from OSF”s software are compatible with WinEEG.
• We were able to save the OSF EEG data as ASCII file type and other file types which are listed as compatible in the WinEEG user manual.
 The software will be used to compute:
• Average frequency of cortex activity for each portion of the music therapy sequence within each major region of the cerebral cortex.
• Average amplitude of combined Alpha-Theta frequency range for each portion of music therapy sequence within each major region of the cerebral cortex.
• Relative duration of Alpha-Theta frequency activity for each portion of the music therapy sequence within each major region of cortex.
• Comparison Tables  and Cortex Mapping functions will also be used.
 See Appendix (entry #4) for more information on WinEEG
 Study could be blinded by having two members of our research team, who are unaware of the music sequences, make the measurements on all EEG wave data. This would allow us to double-check our data.
• IRB
o IRB approval will be sought for this minimal-risk human research study.
o Each study participant will be fully informed of the study”s risks  and benefits before the music therapy session begins.
o Each subject will be informed, before the music therapy session begins, that he/she may verbally withdraw from the study at any time or by removing their blindfold.
o Informed consent will be obtained from each subject before the session begins.

REFERENCES
Baumgartner, T., Esslen, M., and Jancke, L. (2006). From emotion perception to emotion experience: emotions evoked by pictures and classical music. International Journal of Psychophysiology , 34-43.
Conrad, C., Niess, H., Jauch, K.-W., Bruns, C. J., Hartl, W. H., and Welker, L. (2007). Overture for growth hormone: Requiem for interleukin-6? Critical Care Medicine , 2709-2713.
Jacobs, G. D., and Friedman, R. (2004). EEG Spectral Analysis of Relaxation Techniques. Applied Psychophysiology and Biofeedback , 245-254.
Kabuto, M., Kageyama, T., and Nitta, H. (1993). EEG power spectrum changes due to listening to pleasant music and their relation to relaxation effects. Nippon Eiseigaku Zasshi , 807-818.
Kliempt, P., Ruta, D., Ogston, S., Landeck, A., and Martay, K. (1999). Hemispheric-synchronisation during anaesthesia: a double-blind randomised trial using audiotapes for intra-operative nociception control. Anaesthesia , 769-773.
Kolesch, S., Maess, B., Grossmann, T., and Friederici, A. D. (2003). Electrical brain responses reveal gender differences in music processing. NeuroReport: Brain Imaging , 709-713.
Lin, Y.-P., Duann, J.-R., Chen, J.-H., and Jung, T.-P. (2010). Electroencephalographic dynamics of musical emotion and perception revealed by independent spectral components. NeuroReport , 410-415.
University Hospitals Of Cleveland. (2011). History of Music Therapy. Retrieved January 9th, 2011, from University Hospitals Music as Medicine: http://www.musicasmedicine.com/about/history.cfm
Zare, M., Ebrahimi, A. A., and Birashk, B. (2010). The effects of music therapy on reducing agitation in patients with Alzheimer's disease, a pre-post study. International Journal of Geriatric Psychiatry , 1306-1310.

APPENDIX
1) Neurofax EEG-1200A electroencephalograph
• Neurofax EEG-1200 PC-based EEG and polygraph system enables registration, evaluation and analysis of EEG and polygraph data. This technical high-end solution includes amplifiers for recording 38, 44, 64, 128 or 192 channels at sampling frequencies of up to 10,000 Hz. 16 additional DC channels including eight external triggers are available optional. Up to 250 EEG channels can be traced at the same time in real time. The Neurofax EEG-1200 system includes a highly functional and intuitive software package for data recording, playback and quantitative analysis.
• Product URL: http://www.nihonkohden.de/products/neurology/eeg/research/eeg-1200.html?L=1

(remaining portions of study text removed due to length/posting issues)

[Ascension]

Awesome, thanks for posting, I'll read through it all when I get a chance.

[zensphere]

Way to go, Abe!

On skimming the text above, I noticed that you will be using 3 minute long clips of music as your standard stimulus length. Do you think this will be an adequate exposure period to achieve a significant effect? My assumption is that entrainment effects would become more pronounced at increased exposure lengths, but perhaps that could be explored in a future study…

Also, just wanted to point out that the effective Alpha bpm range for 16th note KB is from 120 to 180-195 bpm. Anywhere in there is within the alpha range and Theta would be from 60 to 120 bpm. I think of swamp trance as theta trance…

Hope the study goes well and yields good experimental fruit! 

[Pauldo]

Very awesome Abe!  Haven't read the full text yet butwill be doing so.  I'm wondering what the use of only right handed subjects controls for?  What would be the difference?

[PookztA]

thanks for the comments everyone 🙂

R-handed subjects to ensure that they are left hemisphere-dominant individuals. even L-handed subjects are usually L-hemisphere dominant, but by only looking at R-handed subjects we can look at a more 'standardized' layout of the human brain. (i.e. it is possible that being L-handed may cause more R-hemisphere activity during music therapy, so we are controlling for any differences we might see in EEG brain activity by choosing only R-handed subjects. most people are L-hemisphere dominant anyway so it is more to prevent confounding factors from influencing the data more than anything; aka it increases the quality of the data by eliminating any differences that 'handedness' might create during the EEG recording, therefore allowing the true differences caused by the music to shine through more clearly)

[HARDKORNATE]

I am saddened that you didn't include some brostep in there. I think that data would be just as relevant 😀

[Robyo]

Right on, Abe. Very interesting and fun study.

Much of the newer goa trance does have 16th note basslines. And usually when counting bpm (in dance music, especially), it's the kick drum that determines beats per minute. If one starts adding bassline notes (as in psy) the bpm would be more in the high 500's. What wave state is that? 

Also wondering if “the hypnotic effect” or “trance state” has ever been fully integrated to a particular tempo range. Perhaps the trance state can be achieved at any tempo, but certain states are reportedly more enjoyable than others? Are you familiar with entrainment?

Thanks for reporting the detrimental possibilities and effects of music. Likely you'll get some negative responses as well as positive from your subjects. Music is a powerful tool for science and medicine, but like a double-edged sword, it can be used for destruction (I'm reminded of the traditional use of martial drumming or the newer phenomenon of CIA-approved torture). Certainly a cool project. You are opening up many new questions!

[spycht]

Anywhere in there is within the alpha range and Theta would be from 60 to 120 bpm. I think of swamp trance as theta trance…

Then WTF is neurosludge?

@Abe – Right on. 

[zensphere]

^ 90/180 mid-theta and high alpha  ;D

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