Music & Medicine | 2017 | Volume 9 | Issue 3 | Pages 153 – 166 Bartel, Chen, Alain & Ross | Vibroacoustic

ibroacoustic Stimulation and Brain Oscillation

Full-Length Article

Vibroacoustic Stimulation and Brain Oscillation: From Basic Research to Clinical Application
Lee R. Bartel1, Robert E.W. Chen2, Claude Alain3, Bernhard Ross3
1
University of Toronto, Toronto, Canada
2
Krembil Research Institute, University Health Network, University of Toronto, Toronto, Canada
3
Rotman Research Institute, Baycrest Centre, University of Toronto, Toronto, Canada

Abstract
This paper addresses the importance of steady-state brain oscillation for brain connectivity and cognition. Given that a healthy
brain maintains particular levels of oscillatory activity, we argue that disturbances or dysrhythmias of this oscillatory activity
coincide with common health conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), pain, and depression.
This review shows that electric brain stimulation contributes to regulation of neural oscillatory activity and the alleviation of
related health conditions. It is then argued that specific sound frequencies in their vibratory nature can serve as a means to brain
stimulation through auditory and vibrotactile means and as such can entrain and regulate oscillatory activity. The frequencies
employed and found effective in electric stimulation are reviewed with the intent of guiding the selection of sound frequencies for
vibroacoustic stimulation in the treatment of AD, PD, pain, and depression.

Keywords: neural oscillation, vibroacoustic therapy, brain stimulation, music multilingual abstract | mmd.iammonline.com
medicine, thalamocortical dysrhythmia
Rhythmic Oscillatory Coherence and Connectivity play in coordinating neural activity supporting perceptual,
cognitive, and motor functions [3]. Oscillatory activity may
The origin and function of neural rhythmic oscillatory activity index local neural networks from modality-specific brain
in the brain remains a central research question in areas as well as long-range neural systems that engage sensory
neuroscience. Although several explanations have been and supra-modal brain regions (e.g., prefrontal and parietal
proposed [1], recent work has raised important issues related cortices) [4]. Ward [5] proposed that consciousness is related
to clinical application of oscillatory brain activity in to synchronous neural rhythms in general, but that memory
neurodegenerative diseases and neurorehabilitation [2]. Can processes are related to gamma (30–50Hz) and theta
oscillatory brain activity be used as diagnostic biomarker for oscillatory rhythms, whereas attention is dependent on alpha
conditions like Parkinson’s disease (PD), Alzheimer’s disease and gamma activity. His review of the literature points toward
(AD), and depression? And can oscillatory brain activity be an increased connectivity between frontal and parietal cortex
modulated in support of therapeutic interventions? during memory recall from larger spectral power in gamma
The healthy human brain has intrinsic and constant and theta frequency bands, with the magnitude of gamma
rhythmic oscillation. Popular psychology explained the activity modulated by the theta rhythm. This intra-brain
oscillatory rhythms of “brain waves” as neural indices of communication through neuronal oscillatory coherence is
specific mental states, e.g., delta with sleep (0.1–4Hz), theta thought to index healthy functioning of specific circuits – like
with deep relaxation and creative insight (4–8Hz), alpha with memory, or movement. Although it is well accepted that brain
relaxation (8–12Hz), and beta with problem solving (12– activity related to perceptual, cognitive, and motor functions
20Hz). Although generally true, scientific interest is moving depends on widely distributed neural networks, the functional
toward understanding the role that oscillatory rhythms may connectivity between the nodes of the networks is less well
understood. Fries [6] proposed that the mechanism of
PRODUCTION NOTES: Address correspondence to: neuronal communication depends on similar neuronal
Lee R. Bartel, E-mail: [email protected] | COI statement: The oscillatory activity and that communication within a local
authors declared that no financial support was given for the network (e.g., sensory cortex) happens mainly with coherent
writing of this article. The authors have no conflict of interest to oscillation in the gamma frequency range (30–100 Hz). For
declare.
communication between distant brain areas, the amount of
local gamma oscillations is controlled by slower rhythm in the
theta frequency range (4–8 Hz) [7].

Copyright © 2017 All rights reserved.

International Association for Music & Medicine (IAMM).

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Music & Medicine | 2017 | Volume 9 | Issue 3 | Pages 153 – 166 Bartel, Chen, Alain & Ross | Vibroacoustic Stimulation and Brain Oscillation

Dysregulation of Connectivity within Brain Circuits treatment entails regulation of neural oscillations to their
normal level by either entraining coherent neuronal activity in
Using a musical metaphor, we premise that the healthy brain under-activated circuits or attenuating activity in over-
function depends on a “harmonious symphony” of neuronal activated circuits.
groups oscillating at particular frequencies, which leads to the
supposition, that when one group plays out of tune, too fast or Electric Stimulation of the Brain
too slow, or too high or too low, the “symphony” quickly
turns to “cacophony.” Evidence from using Deep Brain If we accept that the healthy brain requires an array of
Stimulation (DBS – see Electro-stimulation section that optimally functioning neuronal circuits that exist through
follows) as a probe or as a treatment suggests that “circuit” coherent rhythmic brain oscillation and that disease
dysfunction is common to many neurological and psychiatric conditions arise related to a dysfunction of these neural
conditions [8,9]. Essentially, the circuit dysregulations circuits, then brain stimulation that regulates these
underlying these conditions are either (1) a lack of coherence dysfunctional circuits could become a crucial part of
due to inadequate excitation or disturbances to that neurorehabilitation strategies. Electrostimulation is currently
coherence, or (2) overly strong coherence in inappropriate the dominant approach being pursued within medical
neural populations. research and clinical treatment [14].
Llinas was among the first to identify that recurrent
connections between the cortex and the thalamus serve as a Principles of Electric Stimulation
mechanism for interconnecting cortical areas and controlling Electroconvulsive therapy (ECT) involves passing an electrical
the flow of information [9,10,11,12,13]. Using a technical current through the brain, is applied under anesthesia, and
metaphor, thalamocortical loops provide a mechanism for often triggers a seizure. Magnetic Seizure Therapy (MST) is an
communication within the brain like a major hub does for the experimental treatment that can also induce seizures through
internet. According to Llinas, the interconnectivity of stimulation with magnetic fields. Two other types of electrical
thalamocortical loops depends strongly on their rhythmic stimulation include Vagus Nerve Stimulation used for
oscillatory activity. Optimally functioning thalamocortical treatment of seizures and depression, and Transcutaneous
loops show rhythmic activity in the alpha (~10 Hz) and Electrical Nerve Stimulation (TENS) used to control nerve
gamma (~40 Hz) bands. Thalamocortical dysrhythmia (TCD) pain. Recently developed brain stimulation methods are more
is characterized by slowing of alpha oscillatory activity toward focal by limiting the stimulation to a specific target area. For
the theta band at 4–8 Hz and a reduction in gamma band instance, Transcranial Magnetic Stimulation (TMS) and
activity. TCD has been revealed in neurological and repetitive TMS (rTMS) use an electromagnetic coil to
psychiatric conditions related to motor, mood, auditory, and stimulate specific areas of the brain such as the motor cortex.
cognitive functions, and has been linked to conditions Transcranial Direct-Current Stimulation (tDCS) [15] uses
including PD, depression, neurogenic pain, schizophrenia, electrodes placed on specific scalp locations to stimulate the
and tinnitus [10]. brain with a constant low amplitude direct current. tDCS
With the development of DBS, Lozano and others modulates the neuron’s membrane potential. It is divided into
identified neural circuits that are dysfunctional and include positive “anodal” stimulation that increases neural excitability
the wide range of motor, limbic, auditory, executive function, and negative “cathodal” stimulation, which decreases
cognitive, reward, memory, sensory, mood, and interoceptive excitability. Deep Brain Stimulation (DBS) requires surgery
awareness [8]. TCD is thought to be one of the putative and the insertion of electrodes, but offers precise targeting of a
mechanisms underlying several of these dysfunctions. brain area, which is a limitation of the non-invasive methods
However, other circuits/systems likely play a role in these [16]. These electrodes deliver electric pulses from a surgically
dysfunctions including, but not limited to, globus pallidus implanted device. Because of this precise targeting DBS is able
internus over-activity, beta and theta oscillation disturbance, to address specific dysregulated neurological circuits to either
subthalmic nucleus over-activity, orbitofrontal cortex inhibit excessive destructive neural coherence or to excite
hyperactivity, and default mode network dysfunction [8]. The greater positive coherence [8], although the specific
etiologies of “circuit disturbances vary widely and include mechanisms of DBS are not known [17]. See Table 1 for
damage to neural pathways, loss of neural elements and references for the positive effects of electric stimulation.
populations, as well as disturbances in the functional activity
of neural circuits, through disordered firing and pathological
oscillatory activity in neuron ensembles” [8, p. 406].
According to Lozano and Lipsman [8], circuit dysregulation
and its treatment is best illustrated with the “prototypical
conditions” affecting motor, mood, and cognitive circuits: PD,
major depressive disorder, and AD. The approach to

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ECT TMS/rTMS tDCS DBS stimulation, either using more global features of music, for
Parkinson’s Popeo Zanjani et Benninger Lozano & example for inducing mood changes, or employing specific
& al. 2015 et al. 2010 Lipsman rhythms of music at various scales. Both NMT and MSR cross
Kellner [19] [21] 2013 [8],
2009 Gonzalez- Mehanna
over into sound-based stimulation when employing musical
[18] Garcıa et al & Lai 2013 rhythm for interaction between sound and movement. A
2011[20] [22] direct sound stimulation approach is Rhythmic Auditory
Alzheimer’s Burgut Cotelli et al. Hansen Lozano & Stimulation (RAS) [39,40,41], which is used to facilitate
& 2011 [24] 2012 [25] Lipsman movement in Parkinson’s or as rehabilitation with stroke. In
Popeo 2013 [8],
2010 Kaplan
this case, the sounds consist merely of rhythmic clicks or
[23] 2012 [26] claps.
Depression Kellner Weiduschat Ferrucci et Lozano & Auditory stimulation, that is not musical, includes
et al. & Dubin al. 2009 Lipsman Peripheral Ultrasonic Neurostimulation (PUNS), using pulsed
2012 2013 [28] [29] 2013 [8] low frequency ultrasound [42,43,44], and its related
[27]
Pain Mowla Short et al. Lefaucheur Lozano &
application of Transcranial focused ultrasound (tFUS) [45]. The
et al. 2011 [31] et al. 2008 Lipsman latter employs beams of ultrasound most often pulsed at 70–100 Hz
2007 [32] 2013 [8], to target specific areas in the brain with “mechanical” stimulation of
[30] Kaplan the brain tissue. One application is to stimulate brain activity while
2012 [26] another is to change brain function by causing a focal lesion. tFUS
Table 1. Positive Effects of Electric Stimulation has the ability to target specific areas deep in the brain, similar to
DBS. Our interest here is in the stimulation aspect, for which
Underlying Mechanism beneficial effects have been shown with psychiatric disorders
Electric brain stimulation does not interact directly with including depression, chronic pain, and PD.
neural activity in the sense of eliciting neural firing. Instead, A reset is a brief interaction with the dynamics of ongoing
brain stimulation modulates excitability in neural networks oscillation, which effectively reduces the magnitude of the
through a variety of interactions, including (1) blocking oscillation. Acoustic Coordinated Reset (ACR) is a
depolarization, (2) inhibiting synaptic responses, (3) neuromodulation of dysregulated brain circuits, which is
depressing synaptic activity, (4) stimulus-induced modulation based on the concept of Coordinated Reset (CR) in DBS, to
of pathological network activity [33], (5) modulation of reset the firing phase of those neurons that are assumed to
plasticity, and (6) activation of remote but connected areas create the dysregulation [46]. As an intervention for tinnitus,
[1,33]. For rTMS at rates between 10 and 20 Hz, an increase of Tass developed ACR for emulating the effect of CR on the
gamma oscillations in the 30 to 50 Hz range has been found, auditory cortex, and possibly the thalamocortical circuit, using
which is interpreted as indexing perceptual and cognitive audible sounds at the frequency of sound perceived in tinnitus
function. Chen and his associates found significant gamma [47]. The approach was based on the assumption that tinnitus
effects from rTMS and speculated that such stimulation is is a dysregulation of brain circuitry, possibly a thalamocortical
useful as a cognitive enhancing strategy [34]. The stimulant dysrhythmia [9,10] also implicated in PD, depression, and
effect in the 30–50Hz gamma range offers most potential for pain. In tinnitus, ACR was used to “reset” a circuit assumed to
sound stimulation because low frequency sound reaches to be too rhythmically synchronized in its firing. Further
that level but is ineffective for the 10–20Hz range. research is required for testing the possibly easier task of using
pulsed audible sound or reinforcement of rhythmic coherence
Music/Sound Stimulation of the Brain at a particular frequency.
Thaut [35] proposed at least 4 mechanisms at work with
Music, as a multi-faceted cultural product, can be seen as a sound and music: (1) affective-aesthetic response focused on
brain stimulant as it engages several cognitive functions, arousal, motivation, and emotion; (2) patterned information
including associative memory. The importance of music in processing – essentially “thinking music” – music engaging
memory functions has been highlighted by social worker Dan the brain as a language on its own; (3) differential neural
Cohen’s “Music & Memory” organization and their “iPod processing, e.g., language with music and language alone use
Project” (musicandmemory.org) which provides access to different brain pathways; and (4) rhythmic stimulation and
recorded music for the elderly. Treatment approaches that are entrainment. Thaut applied the latter to the rhythm of walking
accompanied by scientific validation include Thaut’s [35]. We argue that rhythmic sound stimulation and
Neurologic Music Therapy (NMT) [35] and Altenmüller’s entrainment can be extended to an even wider frequency
Music Supported Rehabilitation (MSR) [36,37, 38] that use range with steady-state brain stimulation at the rate of
specific music-making tasks to engage a muscular and neural targeted brain activity, ranging from sleep states at delta to the
response. The distinction between music and sound is highly whole sweep of gamma frequencies. We are proposing,
relevant for differentiating the approaches of music therefore, that music/sound is a potential analog to electro-

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stimulation of the brain in the way that sound stimulates Compared to the research using vibrotactile stimulation,
neural activity and contributes to rhythmic neuronal considerably more research has used auditory stimulation for
coherence at particular frequencies. eliciting steady-state or spontaneous oscillatory responses.
Olav Skille in Norway and Petri Lehikoinen in Finland Steady-state response to rhythmic auditory stimuli can be
performed pioneering work in sound stimulation. Lehikoinen elicited using clicks, amplitude-modulated isochronous
[48] developed Physio Acoustic Therapy (PAT) using low sounds [64], or pure tones; for example, a 40 Hz amplitude
frequency sound to stimulate the body by means of modulated tone [65,66], or even the rhythms of binaural beats,
loudspeakers mounted inside a chair. The underlying concept that are created through binaurally detuned tones [50].
is that sound in the range of 27–113 Hz resonates with muscle Common to those methods is that vibrotactile stimulation
fibers, and massages the lymphatic system [49]. The stimulus with sound, as well as auditory stimulation, can be used to
frequency in PAT is continuously varied through the spectral drive a neural response.
range, along with slow pulsation in amplitude, to avoid
adaptation of the mechanoreceptors. PAT and Lehikoinen’s Parkinson’s Disease - Music/Sound Stimulation
chair device was FDA approved in 1996 for three claims:
increased circulation, decreased pain, and increased mobility. Considerable research investigated the concept of rhythmic
Although Lehikoinen never connected the whole-body pulses to stimulate a brain response and to initiate movement
somatosensory stimulation of PAT to an effect on neural in PD. Results showed significant improvement in gait
coherence, it may well contribute to such an effect, despite the performance with rhythmic auditory stimulation (RAS)
continuously changing stimulus frequency. Recent research [39,40,41,67,68]. This applied even when medication had been
demonstrated a driving effect in the auditory modality using withdrawn [69,70]. Rhythmic auditory stimulation produced
binaurally detuned pitch pulsation with continuous variation greater improvement in cadence and stride length compared
over a frequency range similar to PAT [50]. to visual cueing [71]. Improvements through rhythmic cuing
Olav Skille [51] developed Vibroacoustic Therapy (VAT) have also been observed for arm movements [72,73].
using an approach similar to PAT but stimulating with static The effect of whole body vibration on PD symptoms has
low frequency (e.g., at 40, 52, 68 or 86 Hz) instead of been considered since Charcot’s 19th century discovery that
continuously varying the stimulus frequency [52,53]. PD symptoms subsided during a carriage ride [74]. In two
Although a possible interaction with brain activity had been recent reviews, Pinto et al. [75] and Lau et al. [76] reported
considered [54,55], research and clinical efforts primarily that vibration at 6–25 Hz or vibrotactile sound at 30 Hz
assumed an effect on muscle and tissue. The devices designed consistently provided the most positive results.
for VAT and PAT can be used potentially to deliver stimuli at Three studies have used RSS to address PD symptoms
gamma rhythms to the brain through the somatosensory beyond gait: San Vicente et al. [77] studied 60 PD patients; 30
system. A recent pilot study by Clements-Cortes et al. [56] received 25 sessions each 25 minutes long over six months of
used a VAT device to deliver 40 Hz brain stimulation to “relaxing” music plus 40 Hz sine waves applied
Alzheimer’s patients through vibrotactile and auditory means. simultaneously through a bed with integrated vibrotactile
Since both PAT and VAT as low frequency sound stimulation; 30 patients received only the music. Both groups
stimulation (LFSS) generated by special subwoofer-type showed significant improvements on the Unified Parkinson’s
loudspeakers or vibrotactile transducers [57] is experienced Disease Rating Scale (UPDRS), while the 40 Hz group showed
through mechanoreceptors as somatosensory vibration rather a larger gain in the “activities of daily living” scale. The
than – or in addition to – through hearing as audible sound, researcher acknowledged that the music-only treatment also
research on the effects of tactile stimulation applies. Research resulted in a vibration effect since it was played through the
of Rhythmic Sensory Stimulation (RSS) in somatosensory, bed speakers. King et al. [78] studied 40 PD patients (20
auditory, and potentially visual modality, currently being slow/rigid, 20 tremor dominant) not withdrawn from their
pursued by the authors, builds on recent research showing medication. All participants received RSS stimulation at 30 Hz
that vibrotactile stimulation has a strong neural driving effect in five series lasting one minute each separated by one-minute
[58,59,60]. In this previous research we induced effects rest periods. UPDRS scores improved significantly in all major
observed in magnetoencephalography (MEG) from localized symptom categories. Kapur et al. [74] studied 20 patients
mechanical stimulation, using a pneumatic stimulator, treated with recordings of nature sounds and the inherent low
because current sound-driven stimulation on the whole body frequency sounds ranging from 30–500 Hz. One group of ten
involves the use of magnetic transducers, which are participants listened to the recording through headphones
incompatible with MEG sensors. From previous studies it is only, and ten listened to the same headphone sounds but also
known that stimulation of a finger, the hand, or the median received the low frequency sound through a set of transducers
nerve results in an oscillatory response in primary and in the reclining lounge. Participants received 30 minute
secondary sensorimotor cortices [57,61,62] and depends only treatments each day for four weeks in their home with self-
little on attention [63]. reported compliance (93.5%). Results showed significant

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improvement in both groups on the UPDRS Part 1 and Part 3. model of PD, body vibration has considerable history as
While the stimulation targeted the somatosensory system, treatment. There is a known effect from muscular movement
partial transmission of the 30–500 Hz content through the on gamma activity and so potentially might act as a stimulant.
earphones cannot be excluded. Two reviews of whole body vibration research recently show 6
Hz as the most common stimulus with only one using 25 Hz
Finding the Optimum RSS Frequency for Parkinson’s Disease. [75,76]. Studies with rTMS on patients with PD [20,60] use a
The oscillation model of PD places great attention on the range of frequencies below 25 Hz because of technical
subthalmic nucleus (STN) and related motor circuit. Normal limitations and safety considerations, but the mechanism is
motor functions are associated with rhythmic STN activity in not generally considered one of excitation and neural driving.
the 31–100 Hz range with activity between 60–80 Hz being Low frequency sound stimulation through vibrotactile
associated with improved motor performance [79]. The devices is limited to above 27 Hz because transducers are less
typical DBS stimulation frequency that improves symptoms in efficient at lower rate. Two previous RSS studies with PD used
PD is 130–185 Hz, and the frequency that decreases motor 30 Hz [78] and 40 Hz [77]. Assuming neural resonance
function is below 30 Hz [79,80]. Some research showed DBS response up to four multiples, the stimulus frequency [58] for
in the 30–90 Hz range as effective at improving motor optimal sound stimulation of PD could be 40 Hz, eliciting
performance as in the 130–185 Hz range [79]. Given that responses at 40, 80, 120, and 160 Hz, or 80 Hz with responses
stimulation at one frequency also produces a resonant at 80, 160, 240, and 320 Hz. Because a reduction of STN
stimulant response at mathematical multiples (e.g., activity in the 300 Hz range has been observed, and because
stimulation at 20 Hz increases response at 40, 60, and 80 Hz 320 Hz specifically may be a potential biomarker for PD
[58]), a good frequency to emulate DBS stimulation would be [83,84], sound stimulation at 320 Hz could be a possible
about 70–80 Hz, with its first partial resonance being 140–160 target.
Hz [81]. This is also a frequency used by pulsed low frequency
ultrasound [82]. The 160 Hz resonance would be close to 167 Music and Sound Stimulation in Alzheimer’s Disease
Hz, identified as having a crucial role in restoring thalamic
relay function [80]. The effects of music on AD patients have been observed for
An STN rhythm detected in conjunction with dopamine years and inspired a broad range of research. Thaut’s
and apomorphine (peak at about 319 Hz plus or minus 33 Hz) postulated mechanisms for the effect of music [35] are in
is believed to support the basal ganglia circuit’s information essence all forms of brain stimulation: (1) arousal, motivation,
transmission [83,84]. Other research points to 235 Hz [85]. and emotion (2) information processing, and (3) differential
Activity in the 300 Hz range seems also to be correlated with neural processing. Although in one systematic review of music
activity in 60–90 Hz. A reduction of oscillatory activity near therapy studies authors determined there was inadequate
300 Hz may be a potential biomarker for PD [83,84]. The scientific quality [91], other studies have shown the
concern that this effect may be related to advanced state of PD effectiveness of music therapy in AD [92,93,94] but possible
and medication is countered by research showing that 300 Hz brain mechanisms or even neurophysiological changes have
is also observed in other conditions [86]. rarely been shown. Neuroimaging studies found that older
If 300 Hz is an essential oscillatory frequency, and DBS at adults with AD were able to learn new and unfamiliar music
130 Hz proves effective with PD, the question is whether the and that music memory training and familiar melodies
DBS stimulus is only inhibitory, disrupting activity in the enhanced long-term memory for unconnected texts [95,96].
<30Hz area, or is also excitatory, driving activity in the 300 Hz There appears to be a shift in the functional neuroanatomical
range through resonance. This is debated with positive network activated for memory with dementia, i.e., greater use
argument for a direct driving effect [83,84,87] and counter of prefrontal-amygdala connections instead of prefrontal-
evidence of no overtone effect [88]. One issue is that the hippocampal networks [97,98]. That may make music-based
currently approved DBS devices cannot stimulate above 185 encoding more resilient in people with AD [35].
Hz but sound-based RSS can do so easily, and so may have a However, little research has attempted to use vibratory
potent role in treatment. Another good frequency for brain sound frequency as a means to stimulate the oscillatory
stimulation with PD then may be 300 Hz. rhythm of the brain or neural cells. Koike et al. [99] postulated
Three other types of stimulation are worth including. that music may have a role in AD as a catalyst to neural
Electrical Stimulation of the motor cortex [89] is another form regeneration, although they admitted that the mechanisms are
of brain stimulation, however less effective than DBS. The not well understood and proposed that stimulating neural
stimulus frequencies ranged between 10–30 Hz in one study outgrowth with sound may point to a mechanism. The study
and 130 Hz in another and were typically varied across a range used PC12m3 cells cultured in single-cell suspension and
instead of using a single constant frequency. Although the stimulated with nerve growth factor. These cells were then
whole body vibration research does not seem to monitor brain subjected to direct contact vibration with speakers or at a
response and so is not developed based on the oscillatory distance of 12 cm from the speaker. Cells were treated to a

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range of frequencies from 10 Hz to 200 Hz for seven days. streets” carrying traffic to consciousness; pain is subject to
Results showed that all frequencies produced greater modulation by the central nervous system. Emotional state,
outgrowth than the non-vibration control but the greatest anxiety, distraction, past experiences and memories, are
outgrowth occurred when treated with direct vibratory sound among the factors influencing the experience of pain [112].
at 40 Hz. A meta-analysis of 48 studies involving music and pain
Clements-Cortes et al. [56] premised their study on found that in studies where patients were allowed to select
evidence that cognitive deficits in AD are related to reduced preferred music, the effect size was slightly higher (r=.20) than
gamma power around 40 Hz and that vibrotactile and in studies where they were not (r=.18) [94]. Particularly
auditory stimulation can drive oscillatory power and noteworthy, the effect in patients with cancer/terminal
potentially improve cognitive function [12]. The treatment illness/AIDS was considerably higher (r=.45) than in those
was 40 Hz vibrotactile and auditory stimulation two times a post-surgery (r=.15). This points to different effects based on
week for three weeks. Results showed that there was an the nature of the pain.
average effect size of .58 for each session and qualitative Although there have been numerous studies of music and
results that showed some improvements in cognitive clarity pain [94], few have been adequately theorized to explain why
and memory. music reduces pain. Gate Control Theory (GCT) [113]
postulated that pain receptors send information along a
RSS Frequency for Alzheimer’s Disease pathway of interconnected nerves to the brain and that at the
A scientific foundation for oscillatory mechanisms in AD is point where the nerve enters the spinal cord a “gateway”
not as well developed as that for PD. Also, less research with exists that can be open to let the signal through or closed. The
brain stimulation including electro-stimulation has been done gate can be closed by sensory stimulation, like massaging the
and work with DBS is just beginning. Potential stimulation area of the pain, or possibly by vibration along the spine. GCT
frequencies will be inferred from possible dysrhythmias. also maintained that affective and cognitive responses, such as
Findings of thalamocortical dysrhythmia in AD included music-responsive attention and psychological states,
increased power at delta and theta frequencies [100] and a influenced the gate through efferent descending fibers.
power decrease at alpha, beta, and gamma frequencies Although research has shown that GCT oversimplified neural
[100,101,102,103]. Research points to a relationship between systems [114] and the efferent system is not effective, GCT
gamma oscillatory activity and cognitive functions [104]. does help explain why stimulation of touch fibers can reduce
Specifically, research in AD showed decreased spectral power pain perception as is demonstrated with certain applications
around 40 Hz [12,105], although brain activity in this of low frequency sound stimulation (LFSS) that induces
frequency range seems to decrease generally with cognitive mechanical vibrotactile stimulation of mechanoreceptors and
decline and aging [106,107]. Other research reported an spinal cord functioning not unlike electrical skin and spinal
increase in 30–100 Hz gamma band power in AD [101,108] cord stimulation [115]. Melzack [116] proposed a more
without specifically studying 40 Hz activity, yet considering adequate pain theory that would explain the effects of music as
only evoked instead of studying spontaneous activity. The a unified brain mechanism-based body-self neuromatrix
research supported the potential role of theta and gamma (NM). Sensory, cognitive, and affective dimensions are fully
rhythms for biomarkers of early stages of AD [109]. credited with affecting pain perception and these dimensions
Brain stimulation for AD is at an early exploratory stage. are subject to cognitive-evaluative (attention, expectation,
High frequency of 130 Hz has been used in DBS [8] and 20 Hz anxiety, valence) and motivational-affective
in an rTMS study [24]. Gamma-band oscillation can be (neurotransmitter, hormonal, limbic) inputs. Although exact
modulated with low frequency sound or vibrotactile sensory mechanisms are not yet understood, NM provides a
stimulation [104]. 40 Hz, which is decreased in AD, appears to framework to understand why functions of music such as
be a critical frequency for brain stimulation in AD since 40 Hz distraction, stress, and anxiety reduction, and aesthetic
seems generally implicated in brain communication [5,6]. It pleasure reduce pain perception. Neither GCT nor NM
appears to stimulate neural outgrowth [99], and the potential explains pain associated with rhythmic oscillatory coherence
to drive gamma response with auditory or somatosensory [117,118]. The correlation of thalamocortical oscillatory
stimulation has been demonstrated [58,60,64]. dysrhythmia (TCD) with pain has been demonstrated
[10,119] but no definitive theory has been established.
Pain - Music/Sound Stimulation
Effects of Music on Pain
Advances in medical technology, including imaging and non- Given the role that neurotransmitters, hormones, and the
invasive recording of brain activity, have opened new limbic system play in pain according to the Neuromatrix
windows on the structural and physiological dimensions of theory, it is highly relevant that music has been shown to
pain, i.e., a network of brain regions linked to pain in a “pain affect the release of endorphins [120,121,122,123,124,
matrix” [110,111]. Pain pathways are not simple “one-way 125,126,127,128], dopamine [129,130], serotonin [131, 132],

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and decrease in cortisol [130,133,134,135,136,137,138]. A not been previously theorized and conducted as in the present
recent review of 400 published scientific papers found strong study.
evidence that music has effects on brain chemistry and has
mental and physical health benefits on management of mood Deriving an RSS Frequency for Pain
and stress reduction, and that it is the rhythmic stimulation of There is relatively little research that looks at pain as an
music, rather than the melody, that has the greatest anti-pain oscillatory dysregulation except for TCD research and for
effect in the brain [136]. Specific brain correlates can now also electro-stimulation research that, to some extent, is premised
be identified with strong emotional response to music [139]. on dysregulated sensory system circuits [8]. TCD is implicated
Brain imaging shows that “music can modulate activity in in chronic and neuropathic pain with the typical shift of
brain structures that are known to be crucially involved in oscillatory power toward lower frequencies [153,154] and the
emotion, such as the amygdala, nucleus accumbens, edge effect as increased beta activity instead of the more usual
hypothalamus, hippocampus, insula, cingulate cortex and gamma activity. In the case of neuropathic pain the thalamus
orbitofrontal cortex. The potential of music to modulate appears to be more seriously affected to the point of atrophy
activity in these structures has important implications for the [155]. DBS addresses this with stimulation at the typical 130
use of music in the treatment of psychiatric and neurological Hz frequency. The change in alpha power identified in TCD
disorders” [139, p.170]. research is consistent with observations of alpha power related
to placebo analgesia [156]. The hypothesis is that changes in
Effects of Sound Stimulation on Pain alpha activity may be related to expectation of pain relief, with
LFSS stimulates the mechanoreceptors in the body and the change in alpha resulting from either the generation of
cellular structures, thereby serving to potentially block pain expectation, maintenance of expectation, or expression of it.
transmission according to the GCT. In addition to the general Since this is assumed to be a top-down process, manipulation
effects of LFSS, which include improved mobility [140], of alpha activity with stimulation might then be a way to
increased circulation [141], decreased low-density lipoprotein control pain [156]. Since alpha stimulation is possible with
and blood pressure [142], and reduced muscle strain and music and sound, this would be a possible direction for
stiffness [141], LFSS helps decrease pain [141,142]. Studies treatment. Although not placed in conjunction with TCD or
with LFSS have examined specific pain conditions: alpha power, research on “mind wandering away” [157] may
rheumatoid arthritis [143] and polyarthritis in hands and involve the same mechanism by changing coherence and
chest with 40 Hz [144,145], low-back pain, menstrual pain, alpha power.
and dysmenorrhea with 52 Hz [144,145], knee replacement Considerable research has been conducted on the
pain [146], post-operative gynecological pain [147], and application of rTMS in relation to pain. One assumption about
sports injuries [144,145,148]. Despite this research on specific rTMS is that stimulation above 5 Hz is excitatory and
pain, the assumption has primarily been that the effect is stimulation below 1 Hz is inhibitory. In relation to chronic
mechanical cell stimulation and not neurological rhythmic pain, studies have found 10 Hz and 20 Hz to relieve pain but
driving of oscillatory coherence to affect pain circuits. not 0.5, 1, or 5 Hz [87]. This is in agreement with a meta-
analysis of rTMS pain studies showing that, with repeated
Music and Fibromyalgia sessions, treatment around 10 Hz was more effective than
Few studies have focused specifically on music or LFSS on using low frequency stimulation (<1 Hz) or higher frequency
fibromyalgia (FM). Chesky et al. [149] found that musically stimulation >10 Hz [158]. An evidence-based guideline
fluctuating vibration (60–300 Hz) failed to alter pain considered that high frequency rTMS applied to the motor
perception in patients with fibromyalgia. Onieva-Zafra et al. cortex is effective in the treatment of pain [159]. Specifically
[150] examined the effect of 4 weeks daily music listening to with fibromyalgia, 10 Hz was found to be effective [160]. Both
unspecified “classical” music mixed with salsa music. The rTMS and TCD research point to theta and low beta over-
music listening group showed significant reduction in pain as activations that can be ameliorated with stimulation of high
measured by the McGill Pain scale. The control group alpha (10 Hz) [161]. Moreover, motor cortex stimulation
received no treatment and showed no significant change. (MCS) shows some effect at reducing chronic pain (phantom
Müller-Busch and Hoffmann [151] studied chronic pain pain) with stimulation in the 15–25 Hz range [162].
patients including fibromyalgia with a treatment of active MT Sound stimulation for pain was applied in several
using unspecified performed music. The results showed noteworthy studies. Chesky and colleagues [149] used a range
significant reduction in reported pain intensity but no change of frequencies with fibromyalgia in a moving manner rather
in depression and anxiety scores. Leão and da Silva [152] than at fixed frequency and found little effect. Barnes et al.
showed that women with chronic pain had less pain (p<.001) [163] reported decreased pain in a single case with
after listening to classical music. The few studies of sound and fibromyalgia using 25 Hz stimulation with whole body sound
fibromyalgia that exist primarily draw on cognitive and vibration. Naghdi et al. [164] found significant pain reduction
affective effects of music. LFSS and fibromyalgia research has (Fibromyalgia Impact Questionnaire p<.0001) using 40 Hz

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stimulation and pointing to TCD as the probable mechanism greater shift to symmetry with preferred music. Jones and
underlying the effect. Given the findings of oscillatory states Field [173] looked at the effect of massage therapy and 23
with pain, effects from electro-stimulation, and assuming minutes of rock/pop music listening on frontal EEG
downward oscillatory resonance [165], sound stimulation at asymmetry. Except for the addition of massage, this study was
10, 20, or 40 Hz should target the frequencies with greatest a basic replication of Field et al. [172]. Results showed a
treatment potential. similar effect of reduced asymmetry. Im [174] studied frontal
EEG asymmetry in postpartum depressed mothers (n=9)
Depression - Music/Sound Stimulation compared to non-depressed mothers who recently gave birth
(n=9) and 10 non-depressed women who had not given birth.
Music has for many years been regarded as a means to both EEG was recorded for 5 minutes before and after the
engage emotions and to “cheer up.” A classic story in the Old treatment. The length and content of the music session were
Testament has King Saul bothered by “an evil spirit” and not reported. All three groups showed a shift to greater
requests David to play his harp and when David plays, the symmetry after the music session but only for the postpartum
“evil spirit” leaves him. Recently neuroscience is revealing the depressed group was the shift significant (p=.021).
hormonal basis for some of these positive affective Petchkovsky et al. [175] used QEEG data to examine the
correlations with music [121,128,129,130,136,139], as well as effects of depressed adults participating in a choir (1week 8
detailing specific brain components involved in processing weeks) as well as practicing with a prepared practice CD that
emotion with music [139]. Greater detail was already included physical and singing exercises, meditation dialogue,
described in the section on “Pain.” and accompaniments. QEEG results are based on a random
sample (9 from a group of 21), who were tested before and
Music Therapy and Listening after the intervention. Pre- and post-intervention data from
Scientific studies examining the clinical effect of music on the BDI and a mental state examination showed significant
depression are rare. A 2008 Cochrane Review [166] only improvement (p<.001). The resting QEEG data revealed
found five studies that met inclusion criteria requiring greater left-right hemispheric activity symmetry, reduced
therapist-mediated “music therapy” and were too varied to hyperactivity in the right prefrontal area, and reduced
allow a meta-analysis. Findings in four of those studies hypercoherence.
showed a greater reduction in depression symptoms in The only study that recognizes the potential of low
participants treated with music therapy than those receiving frequency stimulation on brain response is Koike et al. [176].
standard care. What “music” was used in the therapy was not In this study 15 elderly adults, who had symptoms of
detailed. Since 2008, a number of studies in both music depression assessed with the Dementia Mood Assessment
therapy and music medicine have been done with important Scale (DMAS), were given 30 minutes (five days/week, two
findings [131,132,167,168,169]. Of these, Brandes et al. weeks) of unspecified “classical” music while resting on a
[131,169] used specifically prepared music that may have lounge chair with two speakers close to the head and
featured an entrainment device for brain stimulation, but frequency crossover at 150 Hz sending the low frequency
details of the proprietary music have not been published. component of the sound to transducers in the body area. A
cognitive assessment was done with the Mini-Mental State
Sound Stimulation of the Brain Exam. The before and after results showed significant
A few music studies have addressed the extensive EEG improvement (p<.05) in the DMAS with significance in the
asymmetry research [170]. This research observed alpha level mood and depression scales but not in the overall dementia
coherent rhythmic oscillatory brain activity and compared left severity scales. No brain imaging was done.
frontal with right frontal activity or activation. There is
considerable evidence that this asymmetry is related to mood Deriving an RSS Frequency for Depression
disorders and may even have a role as a biomarker for Research about oscillatory mechanisms underlying depression
depression [171]. Field et al. [172] used frontal EEG found extensive frontal hemispheric asymmetry in EEG [177].
asymmetry as an observable outcome in a study with 28 Typically this involves a comparison of frontal alpha power in
depressed adolescent females. One group listened for 23 left side versus right side. Although the phenomenon had been
minutes to pop/rock music selected for the study by similar described extensively, underlying mechanisms are not clear
aged girls and the other group was asked to sit and relax their [171], and research on whether frontal asymmetry is a
mind and muscles. Three minute EEG readings were done mediator or moderator of emotions is not clear [170]. If there
before, during, and after the sessions. No changes were were a “causal” role for alpha asymmetry to depression, then
observed in behavior or mood as a result of the treatment, but regulation of the asymmetry would be a treatment, and that
the music group showed decreased frontal asymmetry (p=.05) might be done by stimulating at 10 Hz. Drug treatments for
and decreased cortisol levels (p=.02). A rating of preference depression do seem to restore greater symmetry [177], but
for the music was done and the basic finding supported without knowledge of specific mechanisms it cannot be a firm

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biomarker. Music therapy has been shown to have a positive 6. Fries P. A mechanism for cognitive dynamics: neuronal communication
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10 cases. Pain. 2000; 84: 431-437. Lee Bartel, PhD is Professor in the Faculty of Music with
163. Barnes MJ, McLean SM, Hong J. Fibromyalgia symptoms are reduced by
SonicWave Vibration Therapy: A case study. Clin Kinesiology. 2012; Appointments in the Rehabilitation Sciences Institute and the
66(1): 19-23. Institute of Life Course and Aging at the University of
164. Naghdi L, Ahonen H, Macario P, Bartel L. The effect of low frequency Toronto and was the Founding Director of the Music and
sound stimulation on patients with fibromyalgia: A clinical study. Pain Health Research Collaboratory.
Res Manag. 2015; 20(1): e21-e27.
165. Herrmann CS. Human EEG responses to 1–100 Hz flicker: Resonance
phenomena in visual cortex and their potential correlation to cognitive Robert E W Chen, MA, MSc. is Senior Scientist in the Krembil
phenomena. Exp Brain Res. 2001; 137: 346–353. doi:10.1007/ Research Institute in the University Health Network and
s002210100682. Professor in the Division of Neurology, Department of
166. Maratos A, Gold C, Wang X, Crawford M. Music therapy for depression. Medicine, at the University of Toronto with special interest in
Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: the organization of cortical inhibitory and excitatory pathways
CD004517. doi: 10.1002/14651858.CD004517.pub2.

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in the human motor cortex, pathophysiology of movement and events, specifically short-term memory and selective
disorders, the mechanisms of action of deep brain stimulation attention.
as a treatment of movement disorders.
Bernhard Ross, PhD, is Senior Scientist at the Rotman
Claude Alain, PhD is Assistant Director and Senior Scientist at Research Institute at the Baycrest Centre, Associate Professor
the Rotman Research Institute, Baycrest Centre, and Professor in the Department of Medical Biophysics at the University of
in the Department of Psychology and in the Institute of Toronto, and heads the MEG laboratory with special interest
Medical Sciences, University of Toronto with a specialization in neuromagnetic studies of auditory-motor functions and
in cognitive neuroscience and focus on the brain processes music-supported rehabilitation of stoke patients.
that mediate perception and cognition of auditory patterns

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