Ageing Research Reviews 47 (2018) 133–139

Contents lists available at ScienceDirect

Ageing Research Reviews

journal homepage: www.elsevier.com/locate/arr

Review

Future perspectives on neural mechanisms underlying rhythm and music T

based neurorehabilitation in Parkinson’s disease
⁎
Yuko Koshimori , Michael H. Thaut
Music and Health Science Research Center, Faculty of Music and Collaborative Programs in Neuroscience, University of Toronto, 90 Wellesley Street West, Toronto, Ontario
M5S 1C5, Canada

A R T I C LE I N FO A B S T R A C T

Keywords: Parkinson’s disease (PD) is characterized primarily by a dysfunctional basal ganglia (BG) system, producing
Parkinson’s disease motor and non-motor symptoms. A significant number of studies have demonstrated that rhythmic auditory
Music based interventions stimulation can improve gait and other motor behaviors in PD that are not well managed by the conventional
Rhythmic auditory stimulation therapy. As music, being highly complex stimulus, can modulate brain activity/function in distributed areas of
Neuroimaging
brain, the therapeutic properties of music potentially extend to alleviate non-motor symptoms of PD. Despite the
Auditory-motor entrainment
clinical, behavioral evidence and promises of rhythm and music based interventions, the neural substrates un-
derlying the effectiveness are poorly understood. The goal of this review is to appraise the current state of
knowledge in order to direct further neuroimaging studies that help to determine the therapeutic effects of
rhythm and music based interventions for motor and non-motor symptoms of PD.

1. Introduction movement patterns nearly two decades ago (McIntosh et al., 1997;
Miller et al., 1996; Thaut et al., 1999b, 1996). Entrainment refers to the
Parkinson’s disease (PD) is the second most common age-related frequency locking of two oscillating bodies (Thaut et al., 2015b). In
neurodegenerative disease after Alzheimer’s disease (AD) and the most clinical application of rhythmic entrainment, rhythmic cues serve as
common movement disorder. It affects about 1% of the population aged continuous time reference to initiate and continue motor behaviors. For
over 60 years and 4% of those over 80 in industrial countries. The example, rhythmic auditory cues such as metronome tones, or salient
primary treatment for the cardinal motor symptoms of PD include do- beat embedded in music can help regulate timing and pace in walking
pamine (DA) replacement therapy employing Levodopa and DA ago- (Thaut et al., 2001). Auditory entrainment is superior to the entrain-
nists. Alternative treatment strategies include deep brain stimulation in ment using other sensory systems such as visual and tactile systems
more advanced stages of the disease. However, these conventional because firstly, the auditory system is faster and more precise than the
therapeutic interventions show limited efficacy to alleviate some of the visual and tactile systems to detect temporal patterns (Shelton and
motor impairment such as gait disturbances and freezing of gait (FOG) Kumar, 2010; Thaut et al., 1999a); secondly, the interactions between
as well as non-motor symptoms. They can also impair some of the auditory and motor systems are immediate and stable even below the
cognitive function, as well as develop impulse control disorders in some conscious perception (Thaut et al., 1998); and thirdly, the auditory
of the people with PD, and motor complications such as involuntary system is closely and diffusely connected to the motor system (Thaut
dyskinesia with advancing disease. Because of these limitations, non- et al., 2015a).
conventional therapeutic interventions are of growing interest for PD. In PD, meta-analyses and systematic reviews conveyed general
Rhythm and music based interventions for mobility training have consensus that RAS significantly improved gait parameters such as gait
shown their promises as they are sensory-based, non-invasive, safe, and velocity, cadence, and stride length (Ghai et al., 2018; Lim et al., 2005;
easily accessible without adverse effects (Ashoori et al., 2015; Dalla Rocha et al., 2014; Spaulding et al., 2013). In addition, improvement of
Bella et al., 2015; de Dreu et al., 2012). other motor parameters such as symmetry, gait timing variability (del
Among them, rhythmic auditory stimulation (RAS) has proven its Olmo and Cudeiro, 2005; McIntosh et al., 1997; Miller et al., 1996;
efficacy to improve gait and upper limb disturbances in clinical popu- Willems et al., 2006), step amplitude (Arias and Cudeiro, 2008;
lations including PD since it was first demonstrated to entrain Rochester et al., 2010), pedaling rate (Gallagher et al., 2016), Unified

⁎
Corresponding author.
E-mail address: [email protected] (Y. Koshimori).

https://doi.org/10.1016/j.arr.2018.07.001
Received 11 April 2018; Received in revised form 30 May 2018; Accepted 2 July 2018
Available online 10 July 2018
1568-1637/ © 2018 Elsevier B.V. All rights reserved.
Y. Koshimori, M.H. Thaut Ageing Research Reviews 47 (2018) 133–139

Fig. 1. Subcortical motor pathways associated

with rhythmic movement in (a) normal and (b)
parkinsonian states. The red lines indicate the
projection from the dentate nucleus to the
striatum. The blue lines indicate the projection
from the subthalamic nucleus to the cerebellar
cortex. The yellow lines indicate connections
between pedunculopointine nucleus to basal
ganglia. The green lines indicate connections
in the basal ganglia motor pathway. The black
lines indicate the rest of connections. The
thicker and dashed lines indicate increased and
decreased activities associated with the dis-
ease. The double lines indicate potentially al-
tered activities due to the disease. CM: cen-
tromedian; GPe: external globus pallidus; GPi:
internal globus pallidus; IL: intralaminar; PPN:
pedunculopointine nucleus; SNpc: substantia
nigra pars compacta; SNr: substantia nigra parc
reticularis; STN: subthalamic nucleus; VA:
ventroanterior; VL: ventrolateral.

Parkinson’s Disease Scale (UPDRS) scores (de Bruin et al., 2010; De Icco that RAS may also be able to influence the residual dopaminergic
et al., 2015; Lim et al., 2005), and FOG (Arias and Cudeiro, 2010; function and BG-thalamo-cortical (BGTC) network, and/or the activity
Kadivar et al., 2011; Lee et al., 2012; Nieuwboer et al., 2009) were in the motor pathway between pedunculopontine nucleus (PPN) and BG
reported. Furthermore, gait training with auditory cueing led to some to improve gait impairment in PD. In this review paper, we discuss the
improvement on the motor and perceptual timing tasks in people with motor pathways/networks associated with rhythmic movement (e.g.,
PD (Benoit et al., 2014). The carry over effects of auditory-cueing motor gait) in PD, how auditory stimuli can exert influence on them, sum-
training ranged from four to eight weeks (Benoit et al., 2014; Dalla marizes published neuroimaging data in PD, and presents future di-
Bella et al., 2017; Kadivar et al., 2011; Nieuwboer et al., 2007), but not rections of research in the field of neural plasticity induced by auditory-
three months (De Icco et al., 2015) after the completion of the inter- motor entrainment, implicating the therapeutic effects in PD. Ad-
vention. Regardless of the status of antiparkinsonian medication, ditionaly, we discuss the potential of music based interventions to al-
people with PD could benefit from the motor training with RAS leviate non-motor symptoms of PD.
(McIntosh et al., 1997; Rochester et al., 2010). Although both studies
showed that the improvement in motor behaviors was greater when the
auditory cue was used in the on-medication (ON) state compared to the 2. Motor pathways/networks associated with rhythmic movement
off-medication (OFF) state, the differences were not statistically sig-
nificant. A recent meta-analysis reported that an application of auditory 2.1. Basal ganglia-thalamo-cortical (BGTC) and cerebello-thalamo-cortical
cueing in the ON state yielded large effect sizes for stride length and (CTC) networks
gait velocity while the application of auditory cueing in the OFF state
yielded a large effect size for stride length and a medium effect size for Two major motor networks associated with rhythmic movement
gait velocity (Ghai et al., 2018). These observations suggest that the include basal ganglia-thalamo-cortical (BGTC) and cerebello-thalamo-
restored dopaminergic function contribute to greater effectiveness in cortical (CTC) motor networks. The BGTC network consists of the post-
auditory-motor entrainment. commissural putamen, the internal segment of the globus pallidus,
The use of rhythmic timing has been extended to dance interven- thalamus, and sensorimotor areas while the CTC network consists of the
tions in people with PD (Bloem et al., 2015; Sihvonen et al., 2017). cerebellar cortex and dentate nucleus, thalamus, premotor cortex, and
Tango (Hackney and Earhart, 2009; McKee and Hackney, 2014), Ar- parietal regions. These two networks were considered distinct and their
gentine tango or adapted tango (Allen et al., 2017), Irish setting dance interactions were thought to occur only at the cortical level (Caligiore
(Volpe et al., 2013; but see Shanahan et al., 2017), and music based et al., 2017; Wu and Hallett, 2013). However, recent animal studies
movement therapy (Pohl et al., 2013) alleviated disease severity (Allen revealed the existence of disynaptic connections between BG and cer-
et al., 2017; McKee and Hackney, 2014; Pohl et al., 2013; Volpe et al., ebellum (Fig. 1a): the dentate nucleus projecting to the striatum
2013), as well as improved balance (Allen et al., 2017; Volpe et al., through the thalamus (Hoshi et al., 2005) and the subthalamic nucleus
2013), gait (Allen et al., 2017), FOG (Volpe et al., 2013), cognitive (STN) projecting to the cerebellum through the pontine nuclei (Bostan
function (McKee and Hackney, 2014; Pohl et al., 2013), and quality of et al., 2010). The projection from the dentate nucleus to the striatum
life (Pohl et al., 2013). originates from both motor and non-motor domains of the dentate
Despite the clinical behavioral evidence and promises of rhythm and nucleus (Hoshi et al., 2005) and the projection from the STN to the
music based mobility training, the neural substrates underlying the cerebellum was topographically organized (Bostan et al., 2010). The
effectiveness are poorly understood. This is of particular interest in reciprocal, topographically specific connections between the cere-
people with PD who are characterized by dysfunctional BG as the bellum and BG (Hoshi et al., 2005) indicates that the two structures are
structure subserves important functions in rhythmic motor timing likely to interact to influence motor and non-motor functions.
(Leow and Grahn, 2014; McIntosh et al., 1997). Thus, a question arises A human neuroimaging study also supported the connectivity
how people with PD can benefit from RAS? PD literature hypothesizes (Pelzer et al., 2013). In PD, the OFF state shows both increased and
that RAS recruits a ‘bypass’ network such as cerebello-thalamo-cortical decreased coupling in the motor networks, commonly with decreases
(CTC) motor network (Morris et al., 1996). However, literature suggests within the BGTC motor network and increases within other BGTC
networks and/or CTC motor network (Fig. 1b), and the administration

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of dopaminergic medication restores at least partially the altered brain

activity (Esposito et al., 2013; Wu et al., 2009). Furthermore, PD shows
higher neural activity than normal in the STN (Schrock et al., 2009)
whose neurons are excitatory using glutamatergic neurotransmission
(Smith et al., 1998). The abnormal excitatory signals from the STN
likely increase the cerebellar activity because the pontine nuclei are
also largely glutamatergic (Beitz et al., 1986; Wu and Hallett, 2013)
(Fig. 1b). Deep brain stimulation of the STN normalizes cerebellar ac-
tivation and improves the motor symptoms (Grafton et al., 2006;
Payoux et al., 2004). These observations also indicate close interactions
between the two motor networks. Furthermore, a unified model of
these two networks for timing processing, which is important for motor
control is postulated (Petter et al., 2016), and degeneracy (Edelman and
Gally, 2001; Tononi et al., 1999) occurs in PD, in which the CTC motor
network performs similarly to the BGTC motor network.

2.2. Pedunculopontine nucleus to basal ganglia motor pathway

Pedunculopontine nucleus (PPN) is a target site for deep brain sti-

mulation to alleviate gait and postural impairment as well as FOG of PD
(Huang et al., 2018; Tsang et al., 2012) and has close connections with
BG (Fig. 1a). PPN has connections from the substantia nigra pars re-
ticularis and internal globus pallidus (GPi) and projects to the sub-
stantia nigra pars compacta (SNpc), GPi, dorsolateral striatum, in- Fig. 2. Simplified illustration of auditory-motor connectivity. Green boxes and
tralaminar and ventral thalamus, and ventral tegmental area lines indicate auditory structures and pathways. Blue boxes and lines indicate
(Benarroch, 2013; Mena-Segovia and Bolam, 2017). The ascending motor structures and pathways. Red lines indicate connections between audi-
projections of PPN may be able to induce locomotion by increasing DA tory and motor structures in which rhythm and music can modulate activities in
neuronal activity in the SNpc, releasing DA in the striatum as well as by motor pathways. BG: basal ganglia; CB: cerebellum; CN: cochlear nucleus; SON:
modulating the thalamic activity (Mena-Segovia and Bolam, 2017). superior olivary nucleus; IC: inferior colliculus; MGN: medial geniculate nu-
In summary, the anatomical and functional connectivity data sug- cleus; PN: pontine nucleus; PPN: penduculopontine nucleus.
gest that the cerebellum, BG, and PPN may be able to communicate
with one another (Fig. 1a) to modulate rhythmic motor behavior such connections are topographically organized (Hackett, 2015; Yeterian
as gait and that due to dysfunctional BG, PD shows differential use of and Pandya, 1998), suggesting that different auditory input may be able
the motor networks/pathways during motor behavior (Fig. 1b). to modulate brain activity in other non-auditory areas (Thaut et al.,
2014) and facilitate distinct functions. For example, lack of connections
3. How do rhythmic auditory stimuli influence the motor regions? from the primary auditory areas to the striatum suggests that more
Anatomical and functional connectivity between auditory and complex auditory processing such as music perception may have
motor areas greater impact on the striatal activity.
In addition to these anatomical connections, a resting-state func-
The auditory system is composed of a hierarchical, widely dis- tional MRI (rs-fMRI) study also showed that the STG (BA22) and the
tributed brain pathway encompassing brain regions in the brainstem, posterior putamen were functionally connected in both people with PD
subcortical and cortical regions. Auditory information is conveyed from and healthy older adults (Helmich et al., 2010). Furthermore, func-
the cochlear nuclei to the superior olivary nucleus, the nucleus of the tional MRI studies showed that passive listening to auditory rhythms or
lateral lemniscus and the inferior colliculus in the brain stem, the music activated motor areas such as the BG, cerebellum, premotor
medial geniculate nucleus in the thalamus, and reaches the primary cortex and supplementary motor area (SMA) (Chen et al., 2009, 2008;
auditory cortex through the acoustic radiations originating from the Fujioka et al., 2012, 2010; Grahn and Brett, 2007; Grahn and Rowe,
medical geniculate nucleus (Pickles, 2015) (Fig. 2). 2009; Seger et al., 2013; Thaut et al., 2014).
Auditory regions in the midbrain and brainstem play an important To summarize, the functional and anatomically connectivity data
role in processing temporal regularity. Among them, the IC is most suggest that (1) auditory stimuli can influence the motor pathways/
sensitive to changes in temporal regularity and has connections with networks associated with rhythmic movement such as gait (Fig. 2), (2)
PPN (Motts and Schofield, 2010) whose cholinergic neurons are re- these motor pathways/networks may coordinate with one another to
sponsive to click sounds with broad frequencies (Reese et al., 1995). generate auditory-motor entrainment, and (3) pathological brains such
These suggest that the PPN may involve in auditory-motor entrainment as PD may show differential use of the pathways/networks in response
using RAS. There is also a network of the medial part of the MGN to external cueing (e.g., more reliance on external cueing) during motor
projecting to cholinergic and non-cholinergic neurons in the GP that behavior.
project to the auditory cortex (Moriizumi and Hattori, 1992), which
may also be associated with auditory motor functions. Furthermore,
some neurons in the primary auditory cortex sends direct glutamatergic 4. Neuroimaging studies on auditory-motor entrainment in
projections to the superior olivary complex, as well as the PPN (Motts Parkinson’s disease
and Schofield, 2010), suggesting that auditory stimuli activating the
primary auditory cortex may be able to affect the activity in the PPN Functional neuroimaging studies can reveal changes in brain ac-
and thereby influence the BGTC motor pathway. tivity during auditory-motor entrainment by employing a simple re-
At the cortical level, the acoustic information is further processed petitive motor task (e.g., a finger tapping task) synchronized to RAS
along the temporal lobe from the Heschl gyrus to the superior temporal (e.g., isochronous metronome clicks). This task is commonly referred to
gyrus (STG) as well as to the frontal, cingulate, anterior and posterior as a synchronization (SYNC) task. The changes in brain activity during
parietal, occipital cortices, amygdala and the striatum. These the SYNC task can be contrasted to those during a compatible control

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task such as a continuation (CONT) task in which participants perform the BGTC motor network including the striatum, globus pallidus, and
the same motor task but without RAS to elucidate the role of RAS. substantia nigra (Freedman et al., 1994; Graff-Guerrero et al., 2008;
Alternatively, brain activities are compared before and after the motor Narendran et al., 2006; Willeit et al., 2006).
training using RAS in both people with PD and healthy controls (HC). It is also crucial to determine the neural basis of the optimal audi-
One study reported that people with PD in the ON state (PD-ON) tory stimuli for rhythmic entrainment that will maximize the ther-
showed significantly reduced variabilities of both finger tapping and apeutic effects targeted for PD. In healthy adults, some studies showed
gait, which became compatible to those for HCs after the motor training that rhythmic music appears to be more effective than metronome tones
using RAS (one hour/day, five days/week for four weeks) (del Olmo to improve gait performance in both younger (Leman et al., 2013; Styns
et al., 2006). These patients also showed significantly increased activity et al., 2007) and older (Wittwer et al., 2013) healthy adults. Another
in the right anterior cerebellum and the right parietal and temporal study showed that metronome cues and music with high beat salience
lobes (BA 22, 42, 43) after the training compared to before the training. (high–groove music) elicited similar effects and better effects compared
These findings suggest that strengthened right-lateralized auditory and to music with low beat salience (low-groove music) on gait parameters
corticocerebellar activity may present compensatory/adaptive re- in young healthy adults (Leow et al., 2014). Furthermore, metronome
sponses that emerged after the training using RAS in PD. However, cues were equally effective in improving gait behavior as high-groove
whether the neural plasticity observed in PD would differ from the one familiar music in young healthy adults (Leow et al., 2015). On the
in HCs is unknown as HCs did not have the training. contrary, patients with Huntington’s disease walked faster with the
There is one preliminary functional MRI study that directly con- metronome cues compared to with rhythmic music (Thaut et al.,
trasted brain activity during the SYNC and CONT tasks between PD-ON 1999b).
and HCs, and demonstrated that PD-ON showed greater activity in a The inconsistent findings may be partly due to individual differ-
large neural network including the anterior cingulate and medial ences in beat perception associated with cognitive ability (Leow et al.,
frontal regions, bilateral middle frontal gyri, bilateral parietal lobe, 2014) and cognitive or attentional demands of auditory stimuli
insular cortices, cerebellum, and the body of the caudate nucleus (Thaut (Ashoori et al., 2015; Leow et al., 2015; Thaut et al., 1999b). Thus,
et al., 2015a). A graph theoretical analysis further revealed that PD-ON simple isochronous metronome cueing may elicit greater therapeutic
had a greater functional connectivity within sensorimotor areas con- effects than rhythmic music in patients who are likely to have cognitive
sisting of the left pre- and postcentral gyri and SMA, and between these impairment (Thaut et al., 1999b). People with PD who showed cogni-
motor regions and the auditory cortex in the SYNC condition. These tive impairment measured by MMSE (scores ranging from 22.5 to 25)
findings suggest that the SYNC task activated both CTC and BGTC were able to improve gait behavior with metronome cues (Rochester
networks by consolidating the cortical auditory-motor interactions. The et al., 2009). More studies are needed to determine the effects of dif-
role of dopaminergic medication on RAS-induced enhanced BGTC ferent forms of rhythmic entrainment on brain activity and motor be-
needs to be elucidated. haviors in PD with different cognitive profiles.
Other studies suggest that the SYNC task enhance the activity in
cortical regions in PD. In one study, PD showed a wide distributed 5. Music based interventions for non-motor symptoms of
cortical activation, but not either striatum or cerebellum during the Parkinson’s disease
SNYC task compared to the CONT task (Jahanshahi et al., 2010). In
another study, PD showed that enhanced activation in the right insula Music as a highly complex stimulus (Thaut, 2015) may be able to be
and left inferior parietal cortex (BA40) during the OFF state, and in the applied to alleviate non-motor symptoms of PD. For example, cognitive
left superior frontal gyrus (BA9) and left subcallosal gyrus (BA34) impairment is prevalent in people with PD, particularly executive
during the ON state compared to HCs (Elsinger et al., 2003). In either dysfunctions associated with frontal regions and DA (Schapira et al.,
study, the results of direct contrast of SYNC > CONT between PD and 2017). A recent pilot study including 25 people with PD without de-
HC groups are not reported. mentia or depression demonstrated that a six-week active music inter-
In another study, when the activity in the sub-putaminal regions ventions consisting of production of music, singing, and dancing im-
were specifically analyzed during auditory-cueing ankle movement in proved frontal lobe function as well as memory function (Spina et al.,
PD-ON group compared to HC group, there was no group differences in 2016).
the putaminal activation (Nieuwhof et al., 2017). In both group, the To date, there is no neuroimaging study addressing the brain
dorso-posterior putamen showed significantly greater activity than the changes induced by music based interventions in cognitive impairment
rest of the putaminal subregions (ventro-posterior, sorso-anterior, of PD. However, a randomized controlled study in patients with stroke
ventro-anterior regions). showed that daily listening of favorite music resulted in significant
These few published studies vary in the experimental method (e.g., increase in gray matter (GM) volume in wide areas of brain compared
types and frequencies of RAS presentation or motor responses, types of to listening to an audio book and no intervention (Särkämö et al.,
control task and image contrasts, clinical characteristics of PD and 2014). The cortical GM increase was apparent particularly in the right
medication state), which makes it challenging to draw a conclusion. To frontal regions including the superior, middle, and inferior frontal gyri,
date, there is only one preliminary study that specifically address the orbitofrontal cortex, and superior medial frontal gyrus, in addition to
neural underpinning for auditory-motor entrainment in PD-ON. There the left SMA and left ventral/subgenual anterior cingulate cortex (ACC)
has been no study to address it in the OFF state and therefore, the in- as well as the right precuneus and posterior cingulate cortex in the
teraction between medication and external auditory cueing on motor parietal region and the right fusiform gyrus in the temporal region.
behavior is unknown. Moreover, there has been no study to interrogate Subcortically, the volume increase occurred in the right ventral
the PPN-BG activity during auditory-motor entrainment. Thus, further striatum and ventral GP. Furthermore, the increased GM volume in the
studies are warranted. Pertinent investigations are needed contrasting SFG was associated with better cognitive performance. Cortical thin-
brain activation during SYNC and CONT tasks and during ON and OFF ning in the SFG was associated with executive dysfunction and general
states. To elucidate the effects of RAS on BG activity, it may also be cognitive impairment in people with PD (Koshimori et al., 2015). These
useful to contrast dopaminergic responses during the SNYC task to results suggest that music based interventions may be able to coun-
those during the CONT task using DA PET radioligands such as [11C] teract the cortical thinning and cognitive impairment of PD.
raclopride and [11C]-(+)-PHNO. The latter radioligand may be ad- Depression and anxiety are also part of common non-motor symp-
vantageous as it shows higher sensitivity in detecting changes in ex- toms of PD (Schapira et al., 2017). In the study by Särkämö et al.
tracellular DA induced by external stimuli (Narendran et al., 2010) and (2014), the increased GM volume in the subgenual ACC was associated
shows stronger binding signals in more brain structures associated with with reduced negative mood including depression, tension, fatigue,

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forgetfulness and irritability. Furthermore, a meta-analysis of func- Acknowledgment

tional neuroimaging studies suggests that music in general can mod-
ulate brain activity in various brain regions that are implicated in NA.
psychiatric disturbances such as amygdala, hippocampal formation,
ventral striatum including the ventral pallidum, the head of the caudate References
nucleus, the pre-SMA, cingulate cortex, and orbitofrontal cortex
(Koelsch, 2014). Moreover, highly pleasant music induced DA release in Allen, J.L., McKay, J.L., Sawers, A., Hackney, M.E., Ting, L.H., 2017. Increased neuro-
the ventral and dorsal striatum, which was positively correlated with muscular consistency in gait and balance after partnered, dance-based rehabilitation
in Parkinson’s disease. J. Neurophysiol. 118, 363–373. https://doi.org/10.1152/jn.
degree of pleasure felt in young healthy adults (Salimpoor et al., 2011). 00813.2016.
Taken together, listening to music, particularly favorite or pleasant Arias, P., Cudeiro, J., 2008. Effects of rhythmic sensory stimulation (auditory, visual) on
music may contribute to psychological well-being in PD, which is also gait in Parkinson’s disease patients. Exp. Brain Res. 186, 589–601. https://doi.org/
10.1007/s00221-007-1263-y.
accompanied with structural and functional brain changes. Arias, P., Cudeiro, J., 2010. Effect of rhythmic auditory stimulation on gait in parkinso-
Rhythm and music can also alleviate some of the impairment as- nian patients with and without freezing of gait. PLoS One 5. https://doi.org/10.
sociated with speech in PD (Thaut, 2015). One study investigated the 1371/journal.pone.0009675.
Ashoori, A., Eagleman, D.M., Jankovic, J., 2015. Effects of auditory rhythm and music on
effectiveness of different types of rhythmic components to improve gait disturbances in Parkinson’s disease. Front. Neurol. 6, 234. https://doi.org/10.
speech intelligibility in people with PD who had hypokinetic dysarthria 3389/fneur.2015.00234.
(Thaut et al., 2001). Both metered and patterned rhythmic cueing led to Beitz, A.J., Larson, A.A., Monaghan, P., Altschuler, R.A., Mullett, M.M., Madl, J.E., 1986.
Immunohistochemical localization of glutamate, glutaminase and aspartate amino-
significant improvement in speech intelligibility rates in these patients.
transerase in neurons of the pontine nuclei of the rat. Neuroscience 17, 741–753.
In addition, there was a case study in PD demonstrating that the pre- Benarroch, E.E., 2013. Pedunculopontine nucleus: functional organization and clinical
sence of march that is more congruent with the predominant meter of implications. Neurology 80, 1148–1155. https://doi.org/10.1212/WNL.
the language, but not waltz that is not congruent with that, improved 0b013e3182886a76.
Benoit, C.E., Dalla Bella, S., Farrugia, N., Obrig, H., Mainka, S., Kotz, S.A., 2014.
speech perception. This was also accompanied with a robust evoked Musically cued gait-training improves both perceptual and motor timing in
potential response demonstrated using EEG (Kotz and Gunter, 2015). Parkinson’s disease. Front. Hum. Neurosci. 8. https://doi.org/10.3389/fnhum.2014.
In summary, the brain regions whose activity modulated by music 00494.
Bloem, B.R., de Vries, N.M., Ebersbach, G., 2015. Nonpharmacological treatments for
well overlap with those in the cortico-striatal circuits, suggesting the patients with Parkinson’s disease. Mov. Disord. 30, 1504–1520. https://doi.org/10.
potential therapeutic effects of music to partially alleviate non-motor 1002/mds.26363.
symptoms of PD such as cognitive impairment and psychological dis- Bostan, A.C., Dum, R.P., Strick, P.L., 2010. The basal ganglia communicate with the
cerebellum. Proc. Natl. Acad. Sci. U. S. A. 107, 8452–8456. https://doi.org/10.1073/
turbances. Interestingly, the results reported by Särkämö et al. (2014) pnas.1000496107.
were only present in the stroke patients with left hemispheric damage. Caligiore, D., Pezzulo, G., Baldassarre, G., Bostan, A.C., Strick, P.L., Doya, K., Helmich,
This may be related to the right hemisphere dominance of music pro- R.C., Dirkx, M., Houk, J., Jörntell, H., Lago-Rodriguez, A., Galea, J.M., Miall, R.C.,
Popa, T., Kishore, A., Verschure, P.F.M.J., Zucca, R., Herreros, I., 2017. Consensus
cessing (Zatorre et al., 2007). It may be interesting to investigate the paper: towards a systems-level view of cerebellar function: the interplay between
relationship between the laterality of music processing and the side of cerebellum, basal ganglia, and cortex. Cerebellum 16, 203–229. https://doi.org/10.
symptom dominance in people with PD. In addition, future research is 1007/s12311-016-0763-3.
Chen, J.L., Penhune, V.B., Zatorre, R.J., 2008. Listening to musical rhythms recruits
needed to uncover the specific neural mechanisms underlying how
motor regions of the brain. Cereb. Cortex 18, 2844–2854. https://doi.org/10.1093/
rhythm and music improve speech impairment in PD. cercor/bhn042.
Chen, J.L., Penhune, V.B., Zatorre, R.J., 2009. The role of auditory and premotor cortex in
sensorimotor transformations. Ann. N. Y. Acad. Sci. 1169, 15–34. https://doi.org/10.
1111/j.1749-6632.2009.04556.x.
6. Conclusion and future directions Dalla Bella, S., Berkowska, M., Sowiński, J., 2015. Moving to the beat and singing are
linked in humans. Front. Hum. Neurosci. 9, 1–13. https://doi.org/10.3389/fnhum.
At present, due to a paucity of literature specifically investigating 2015.00663.
Dalla Bella, S., Farrugia, N., Benoit, C.-E., Begel, V., Verga, L., Harding, E., Kotz, S.A.,
the effects of RAS and music on brain dysfunction underlying motor and 2017. BAASTA: battery for the assessment of auditory sensorimotor and timing
non-motor symptoms in PD, a full understanding of the neural sub- abilities. Behav. Res. Methods 49, 1128–1145. https://doi.org/10.3758/s13428-016-
strates underlying the therapeutic effects await further research. 0773-6.
de Bruin, N., Doan, J.B., Turnbull, G., Suchowersky, O., Bonfield, S., Hu, B., Brown, L.A.,
However, important key findings in the literature shows already that 2010. Walking with music is a safe and viable tool for gait training in Parkinson’s
rhythm and music modulate the brain activity in the DA pathways and disease: the effect of a 13-week feasibility study on single and dual task walking.
DA release in the striatum, as well as the brain activity in the associated Parkinsons Dis. 2010, 1–9. https://doi.org/10.4061/2010/483530.
de Dreu, M.J., van der Wilk, A.S.D., Poppe, E., Kwakkel, G., van Wegen, E.E.H., 2012.
regions/network such as the cerebellum possibly as a compensatory/
Rehabilitation, exercise therapy and music in patients with Parkinson’s disease: a
adaptive mechanism, amygdala, parietal regions and PPN. Therefore, meta-analysis of the effects of music-based movement therapy on walking ability,
rhythm and music based interventions have promises for com- balance and quality of life. Parkinsonism Relat. Disord. 18, S114–S119. https://doi.
org/10.1016/S1353-8020(11)70036-0.
plementary therapy for PD, by likely inducing positive effects on dis-
De Icco, R., Tassorelli, C., Berra, E., Bolla, M., Pacchetti, C., Sandrini, G., 2015. Acute and
ease associated regions and/or facilitating compensatory mechanisms. chronic effect of acoustic and visual cues on gait training in Parkinson’s disease: a
The literature also suggests that different auditory stimuli may vary in randomized, controlled study. Parkinsons Dis. 2015, 978590. https://doi.org/10.
their therapeutic effects. However, the consistent point in the research 1155/2015/978590.
del Olmo, M.F., Cudeiro, J., 2005. Temporal variability of gait in Parkinson disease: ef-
literature in this respect seems to be the emphasis on an isochronous fects of a rehabilitation programme based on rhythmic sound cues. Parkinsonism
rhythmic stimulus structure to optimally facilitate the effects. Further Relat. Disord. 11, 25–33. https://doi.org/10.1016/j.parkreldis.2004.09.002.
neuroimaging studies, especially with an emphasis on functional con- del Olmo, M.F., Arias, P., Furio, M.C., Pozo, M.A., Cudeiro, J., 2006. Evaluation of the
effect of training using auditory stimulation on rhythmic movement in Parkinsonian
nectivity and neurotransmitter functions, are needed to elucidate the patients-a combined motor and [18F]-FDG PET study. Parkinsonism Relat. Disord.
relationship between rhythm and music based interventions and their 12, 155–164. https://doi.org/10.1016/j.parkreldis.2005.11.002.
therapeutic effects on motor and non-motor symptoms of PD. Edelman, G.M., Gally, J.A., 2001. Degeneracy and complexity in biological systems. Proc.
Natl. Acad. Sci. U. S. A. 98, 13763–13768.
Elsinger, C.L., Rao, S.M., Zimbelman, J.L., Reynolds, N.C., Blindauer, K.A., Hoffmann,
R.G., 2003. Neural basis for impaired time reproduction in Parkinson’s disease: an
Funding fMRI study. J. Int. Neuropsychol. Soc. 9, 1088–1098.
Esposito, F., Tessitore, A., Giordano, A., De Micco, R., Paccone, A., Conforti, R., Pignataro,
G., Annunziato, L., Tedeschi, G., 2013. Rhythm-specific modulation of the sensor-
This work was supported by Faculty of Music, University of Toronto. imotor network in drug-naive patients with Parkinson’s disease by levodopa. Brain
Michael H. Thaut is supported by the Canada Research Chair Program. 136, 710–725. https://doi.org/10.1093/brain/awt007.
Freedman, S.B., Patel, S., Marwood, R., Emms, F., Seabrook, G.R., Knowles, M.R.,

137
Y. Koshimori, M.H. Thaut Ageing Research Reviews 47 (2018) 133–139

McAllister, G., 1994. Expression and pharmacological characterization of the human Mena-Segovia, J., Bolam, J.P., 2017. Rethinking the pedunculopontine nucleus: from
D3 dopamine receptor. J. Pharmacol. Exp. Ther. 268, 417–426. cellular organization to function. Neuron 94, 7–18. https://doi.org/10.1016/j.
Fujioka, T., Zendel, B.R., Ross, B., 2010. Endogenous neuromagnetic activity for mental neuron.2017.02.027.
hierarchy of timing. J. Neurosci. 30, 3458–3466. https://doi.org/10.1523/ Miller, R.A., Thaut, M.H., McIntosh, G.C., Rice, R.R., 1996. Components of EMG sym-
JNEUROSCI.3086-09.2010. metry and variability in parkinsonian and healthy elderly gait. Electroencephalogr.
Fujioka, T., Trainor, L.J., Large, E.W., Ross, B., 2012. Internalized timing of isochronous Clin. Neurophysiol. Electromyogr. Mot. Control 101, 1–7. https://doi.org/10.1016/
sounds is represented in neuromagnetic beta oscillations. J. Neurosci. 32, 1791–1802. 0013-4694(95)00209-X.
https://doi.org/10.1523/JNEUROSCI.4107-11.2012. Moriizumi, T., Hattori, T., 1992. Choline acetyltransferase-immunoreactive neurons in
Gallagher, R., Damodaran, H., Werner, W.G., Powell, W., Deutsch, J.E., 2016. Auditory the rat entopeduncular nucleus. Neuroscience 46, 721–728. https://doi.org/10.
and visual cueing modulate cycling speed of older adults and persons with 1016/0306-4522(92)90158-X.
Parkinson’s disease in a Virtual Cycling (V-Cycle) system. J. Neuroeng. Rehabil. 13, Morris, M.E., Iansek, R., Matyas, T.A., Summers, J.J., 1996. Stride length regulation in
77. https://doi.org/10.1186/s12984-016-0184-z. Parkinsons’ disease. Normalization strategies and underlying mechanisms. Brain 119,
Ghai, S., Ghai, I., Schmitz, G., Effenberg, A.O., 2018. Effect of thythmic auditory cueing 551–568.
on parkinsonian gait: a systematic review and meta-analysis. Sci. Rep. 8, 1. https:// Motts, S.D., Schofield, B.R., 2010. Cholinergic and non-cholinergic projections from the
doi.org/10.1038/s41598-017-16232-5. pedunculopontine and laterodorsal tegmental nuclei to the medial geniculate body in
Graff-Guerrero, A., Willeit, M., Ginovart, N., Mamo, D., Mizrahi, R., Rusjan, P., Vitcu, I., guinea pigs. Front. Neuroanat. 4, 1–8. https://doi.org/10.3389/fnana.2010.00137.
Seeman, P., Wilson, A.A., Kapur, S., 2008. Brain region binding of the D2/3 agonist Narendran, R., Slifstein, M., Guillin, O., Hwang, Y., Hwang, D.R., Scher, E., Reeder, S.,
[11C]-(+)- PHNO and the D2/3 antagonist [11C]raclopride in healthy humans. Hum. Rabiner, E., Laruelle, M., 2006. Dopamine (D2/3) receptor agonist Positron Emission
Brain Mapp. 29. https://doi.org/10.1002/hbm.20392. Tomography radiotracer [11C]-(+)-PHNO is a D3 receptor preferring agonist in vivo.
Grafton, S.T., Turner, R.S., Desmurget, M., Bakay, R., Delong, M., Vitek, J., Crutcher, M., Synapse 60, 485–495. https://doi.org/10.1002/syn.20325.
2006. Normalizing motor-related brain activity: subthalamic nucleus stimulation in Narendran, R., Mason, N.S., Laymon, C.M., Lopresti, B.J., Velasquez, N.D., May, M.A.,
Parkinson disease. Neurology 66, 1192–1199. https://doi.org/10.1212/01.wnl. Kendro, S., Martinez, D., Mathis, C.A., Frankle, W.G., 2010. A comparative evaluation
0000214237.58321.c3. of the dopamine D(2/3) agonist radiotracer [11C](-)-N-propyl-norapomorphine and
Grahn, J.A., Brett, M., 2007. Rhythm and beat perception in motor areas of the brain. J. antagonist [11C]raclopride to measure amphetamine-induced dopamine release in
Cogn. Neurosci. 19, 893–906. https://doi.org/10.1162/jocn.2007.19.5.893. the human striatum. J. Pharmacol. Exp. Ther. 333, 533–539. https://doi.org/10.
Grahn, J.A., Rowe, J.B., 2009. Feeling the beat: premotor and striatal interactions in 1124/jpet.109.163501.
musicians and nonmusicians during beat perception. J. Neurosci. 29, 7540–7548. Nieuwboer, A., Kwakkel, G., Rochester, L., Jones, D., van Wegen, E., Willems, A.M.,
https://doi.org/10.1523/JNEUROSCI.2018-08.2009. Chavret, F., Hetherington, V., Baker, K., Lim, I., 2007. Cueing training in the home
Hackett, T.A., 2015. Anatomic organization of the auditory cortex. In: Celesia, G.G., improves gait-related mobility in Parkinson’s disease: the RESCUE trial. J. Neurol.
Hickok, G. (Eds.), Handbook of Clinical Neurology. Elsevier B.V., Amsterdam, pp. Neurosurg. Psychiatry 78, 134–140. https://doi.org/10.1136/jnnp.200X.097923.
27–53. Nieuwboer, A., Baker, K., Willems, A.-M., Jones, D., Spildooren, J., Lim, I., Kwakkel, G.,
Hackney, M.E., Earhart, G.M., 2009. Effects of dance on movement control in Parkinson’s Van Wegen, E., Rochester, L., 2009. The short-term effects of different cueing mod-
disease: a comparison of Argentine tango and American ballroom. J. Rehabil. Med. alities on turn speed in people with Parkinson’s disease. Neurorehabil. Neural Rep.
41, 475–481. https://doi.org/10.2340/16501977-0362. 23, 831–836. https://doi.org/10.1177/1545968309337136.
Helmich, R.C., Derikx, L.C., Bakker, M., Scheeringa, R., Bloem, B.R., Toni, I., 2010. Spatial Nieuwhof, F., Bloem, B.R., Reelick, M.F., Aarts, E., Maidan, I., Mirelman, A., Hausdorff,
remapping of cortico-striatal connectivity in Parkinson’s disease. Cereb. Cortex 20, J.M., Toni, I., Helmich, R.C., 2017. Impaired dual tasking in Parkinson’s disease is
1175–1186. https://doi.org/10.1093/cercor/bhp178. associated with reduced focusing of cortico-striatal activity. Brain 140, 1384–1398.
Hoshi, E., Tremblay, L., Féger, J., Carras, P.L., Strick, P.L., 2005. The cerebellum com- https://doi.org/10.1093/brain/awx042.
municates with the basal ganglia. Nat. Neurosci. 8, 1491–1493. https://doi.org/10. Payoux, P., Remy, P., Damier, P., Miloudi, M., Loubinoux, I., Pidoux, B., Gaura, V.,
1038/nn1544. Rascol, O., Samson, Y., Agid, Y., 2004. Subthalamic nucleus stimulation reduces
Huang, C., Chu, H., Zhang, Y., Wang, X., 2018. Deep brain stimulation to alleviate abnormal motor cortical overactivity in Parkinson disease. Arch. Neurol. 61,
freezing of gait and cognitive dysfunction in Parkinson’s disease: update on current 1307–1313. https://doi.org/10.1001/archneur.61.8.1307.
research and future perspectives. Front. Neurosci. 12, 29. https://doi.org/10.3389/ Pelzer, E.A., Hintzen, A., Goldau, M., von Cramon, D.Y., Timmermann, L., Tittgemeyer,
fnins.2018.00029. M., 2013. Cerebellar networks with basal ganglia: feasibility for tracking cerebello-
Jahanshahi, M., Jones, C.R.G., Zijlmans, J., Katzenschlager, R., Lee, L., Quinn, N., Frith, pallidal and subthalamo-cerebellar projections in the human brain. Eur. J. Neurosci.
C.D., Lees, A.J., 2010. Dopaminergic modulation of striato-frontal connectivity 38, 3106–3114. https://doi.org/10.1111/ejn.12314.
during motor timing in Parkinson’s disease. Brain 133, 727–745. https://doi.org/10. Petter, E.A., Lusk, N.A., Hesslow, G., Meck, W.H., 2016. Interactive roles of the cere-
1093/brain/awq012. bellum and striatum in sub-second and supra-second timing: support for an initiation,
Kadivar, Z., Corcos, D.M., Foto, J., Hondzinski, J.M., 2011. Effect of step training and continuation, adjustment, and termination (ICAT) model of temporal processing.
rhythmic auditory stimulation on functional performance in Parkinson patients. Neurosci. Biobehav. Rev. 71, 739–755.
Neurorehabil. Neural Rep. 25, 626–635. https://doi.org/10.1177/ Pickles, J.O., 2015. Auditory pathways: anatomy and physiology. In: Celesia, G.G.,
1545968311401627. Hickok, G. (Eds.), Handbook of Clinical Neurology. Elsevier B.V., Amsterdam, pp.
Koelsch, S., 2014. Brain correlates of music-evoked emotions. Nat. Rev. Neurosci. 15, 3–25.
170–180. https://doi.org/10.1038/nrn3666. Pohl, P., Dizdar, N., Hallert, E., 2013. The Ronnie Gardiner rhythm and music method – a
Koshimori, Y., Segura, B., Christopher, L., Lobaugh, N., Duff-Canning, S., Mizrahi, R., feasibility study in Parkinson’s disease. Disabil. Rehabil. 35, 2197–2204. https://doi.
Hamani, C., Lang, A.E., Aminian, K., Houle, S., Strafella, A.P., 2015. Imaging changes org/10.3109/09638288.2013.774060.
associated with cognitive abnormalities in Parkinson’s disease. Brain Struct. Funct. Reese, N.B., Garciarill, E., Skinner, R.D., 1995. Auditory input to the pedunculopontine
220, 2249–2261. https://doi.org/10.1007/s00429-014-0785-x. nucleus: I. Evoked potentials. Brain Res. Bull. 37, 257–264.
Kotz, S.A., Gunter, T.C., 2015. Can rhythmic auditory cuing remediate language-related Rocha, P.A., Porfírio, G.M., Ferraz, H.B., Trevisani, V.F., 2014. Effects of external cues on
deficits in Parkinson’s disease? Ann. N. Y. Acad. Sci. 1337, 62–68. https://doi.org/10. gait parameters of Parkinson’s disease patients: a systematic review. Clin. Neurol.
1111/nyas.12657. Neurosurg. 124, 127–134.
Lee, S.J., Yoo, J.Y., Ryu, J.S., Park, H.K., Chung, S.J., 2012. The effects of visual and Rochester, L., Burn, D.J., Woods, G., Godwin, J., Nieuwboer, A., 2009. Does auditory
auditory cues on freezing of gait in patients with Parkinson disease. Am. J. Phys. Med. rhythmical cueing improve gait in people with Parkinson’s disease and cognitive
Rehabil. 91, 2–11. https://doi.org/10.1097/PHM.0b013e31823c7507. impairment? A feasibility study. Mov. Disord. 24, 839–845. https://doi.org/10.1002/
Leman, M., Moelants, D., Varewyck, M., Styns, F., van Noorden, L., Martens, J.P., 2013. mds.22400.
Activating and relaxing music entrains the speed of beat synchronized walking. PLoS Rochester, L., Rafferty, D., Dotchin, C., Msuya, O., Minde, V., Walker, R.W., 2010. The
One 8. https://doi.org/10.1371/journal.pone.0067932. effect of cueing therapy on single and dual-task gait in a drug naïve population of
Leow, L.A., Grahn, J.A., 2014. Neural mechanisms of rhythm perception: present findings people with Parkinson’s disease in Northern Tanzania. Mov. Disord. 25, 906–911.
and future direction. Adv. Exp. Med. Biol. 829, 325–338. https://doi.org/10.1007/ https://doi.org/10.1002/mds.22978.
978-1-4939-1782-2_17. Salimpoor, V.N., Benovoy, M., Larcher, K., Dagher, A., Zatorre, R.J., 2011. Anatomically
Leow, L.A., Parrott, T., Grahn, J.A., 2014. Individual differences in beat perception affect distinct dopamine release during anticipation and experience of peak emotion to
gait responses to low- and high-groove music. Front. Hum. Neurosci. 8. https://doi. music. Nat. Neurosci. 14, 257–262. https://doi.org/10.1038/nn.2726.
org/10.3389/fnhum.2014.00811. Särkämö, T., Ripollés, P., Vepsäläinen, H., Autti, T., Silvennoinen, H.M., Salli, E., Laitinen,
Leow, L.A., Rinchon, C., Grahn, J., 2015. Familiarity with music increases walking speed S., Forsblom, A., Soinila, S., Rodríguez-Fornells, A., 2014. Structural changes induced
in rhythmic auditory cuing. Ann. N. Y. Acad. Sci. 1337, 53–61. https://doi.org/10. by daily music listening in the recovering brain after middle cerebral artery stroke: a
1111/nyas.12658. voxel-based morphometry study. Front. Hum. Neurosci. 8. https://doi.org/10.3389/
Lim, I., van Wegen, E., de Goede, C., Deutekom, M., Nieuwboer, a, Willems, a, Jones, D., fnhum.2014.00245.
Rochester, L., Kwakkel, G., 2005. Effects of external rhythmical cueing on gait in Schapira, A.H.V., Chaudhuri, K.R., Jenner, P., 2017. Non-motor features of Parkinson
patients with Parkinson’s disease: a systematic review. Clin. Rehabil. 19, 695–713. disease. Nat. Rev. Neurosci. 18, 435–450. https://doi.org/10.1038/nrn.2017.62.
https://doi.org/10.1191/0269215505cr906oa. Schrock, L.E., Ostrem, J.L., Tumer, R.S., Shimamoto, S.A., Starr, P.A., 2009. The sub-
McIntosh, G.C., Brown, S.H., Rice, R.R., Thaut, M.H., 1997. Rhythmic auditory-motor thalamic nucleus in primary dystonia: single-unit discharge characteristics. J.
facilitation of gait patterns in patients with Parkinson’s disease. J. Neurol. Neurosurg. Neuropshysiol. 102, 3740–3752.
Psychiatry 62, 22–26. https://doi.org/10.1136/jnnp.62.1.22. Seger, C.A., Spiering, B.J., Sares, A.G., Quraini, S.I., Alpeter, C., David, J., Thaut, M.H.,
McKee, K.E., Hackney, M.E., 2014. The four square step test in individuals with 2013. Corticostriatal contributions to musical expectancy perception. J. Cogn.
Parkinson’s disease: association with executive function and comparison with older Neurosci. 25, 1062–1077. https://doi.org/10.1162/jocn_a_00371.
adults. NeuroRehabilitation 35, 279–289. https://doi.org/10.3233/NRE-141122. Shanahan, J., Morris, M.E., Bhriain, O.N., Volpe, D., Lynch, T., Clifford, A.M., 2017.

138
Y. Koshimori, M.H. Thaut Ageing Research Reviews 47 (2018) 133–139

Dancing for Parkinson’s: a randomized trial of Irish set dancing compared to usual Sci. 4, 428–452. https://doi.org/10.3390/brainsci4020428.
care. Arch. Phys. Med. Rehabil. 98, 1744–1751. https://doi.org/10.1016/j.apmr. Thaut, M.H., Braunlich, K., Kluger, B., McIntosh, G., Seger, C., 2015a. Rhythmic Auditory
2017.02.017. Cues Shape Neural Network Plasticity Underlying Motor Control in Parkinson’s
Shelton, J., Kumar, G.P., 2010. Comparison between auditory and visual simple reaction Disease. Program No. 301.15. 2015 Neuroscience Meeting Planner. Society for
times. Neurosci. Med. 1, 30–32. https://doi.org/10.4236/nm.2010.11004. Neuroscience, Washington, DC Online.
Sihvonen, A.J., Särkämö, T., Leo, V., Tervaniemi, M., Altenmüller, E., Soinila, S., 2017. Thaut, M.H., McIntosh, G.C., Hoemberg, V., 2015b. Neurobiological foundations of
Music-based interventions in neurological rehabilitation. Lancet Neurol. 16, neurologic music therapy: rhythmic entrainment and the motor system. Front.
648–660. https://doi.org/10.1016/S1474-4422(17)30168-0. Psychol. https://doi.org/10.3389/fpsyg.2015.01185.
Smith, Y., Bevan, M.D., Shink, E., Bolam, J.P., 1998. Microcircuitry of the direct and Tononi, G., Sporns, O., Edelman, G.M., 1999. Measures of degeneracy and redundancy in
indirect pathways of the basal ganglia. Neuroscience 86, 353–387. biological networks. Proc. Natl. Acad. Sci. U. S. A. 96, 3257–3262.
Spaulding, S.J., Barber, B., Colby, M., Cormack, B., Mick, T., Jenkins, M.E., 2013. Cueing Tsang, E.W., Hamani, C., Moro, E., Mazzella, F., Poon, Y.Y., Lozano, A.M., Chen, R., 2012.
and gait improvement among people with Parkinson’s disease: a meta-analysis. Arch. Subthalamic deep brain stimulation at individualized frequencies for Parkinson’s
Phys. Med. Rehabil. 94, 562–570. https://doi.org/10.1016/j.apmr.2012.10.026. disease. Neurology 78, 1930–1938. https://doi.org/10.1212/WNL.
Spina, E., Barone, P., Mosca, L.L., Forges Davanzati, R., Lombardi, A., Longo, K., Iavarone, 0b013e318259e183.
A., Amboni, M., 2016. Music therapy for motor and nonmotor symptoms of Volpe, D., Signorini, M., Marchetto, A., Lynch, T., Morris, M.E., 2013. A comparison of
Parkinson’s disease: a prospective, randomized, controlled, single-blinded study. J. Irish set dancing and exercises for people with Parkinson’s disease: a phase II feasi-
Am. Geriatr. Soc. 64, e36–39. https://doi.org/10.1111/jgs.14295. bility study. BMC Geriatr. 13, 54. https://doi.org/10.1186/1471-2318-13-54.
Styns, F., van Noorden, L., Moelants, D., Leman, M., 2007. Walking on music. Hum. Mov. Willeit, M., Ginovart, N., Kapur, S., Houle, S., Hussey, D., Seeman, P., Wilson, A.A., 2006.
Sci. 26, 769–785. https://doi.org/10.1016/j.humov.2007.07.007. High-affinity states of human brain dopamine D2/3 receptors imaged by the agonist
Thaut, M.H., 2015. The discovery of human auditory-motor entrainment and its role in [11C]-(+)-PHNO. Biol. Psychiatry 59, 389–394. https://doi.org/10.1016/j.biopsych.
the development of neurologic music therapy. Prog. Brain Res. 217, 253–266. 2005.09.017.
https://doi.org/10.1016/bs.pbr.2014.11.030. Willems, A.M., Nieuwboer, A., Chavret, F., Desloovere, K., Dom, R., Rochester, L., Jones,
Thaut, M.H., McIntosh, G.C., Rice, R.R., Miller, R.A., Rathbun, J., Brault, J.M., 1996. D., Kwakkel, G., Van Wegen, E., 2006. The use of rhythmic auditory cues to influence
Rhythmic auditory stimulation in gait training for Parkinson’s disease patients. Mov. gait in patients with Parkinson’s disease, the differential effect for freezers and non-
Disord. 11, 193–200. https://doi.org/10.1002/mds.870110213. freezers, an explorative study. Disabil. Rehabil. 28, 721–728. https://doi.org/10.
Thaut, M.H., Miller, R.A., Schauer, L.M., 1998. Multiple synchronization strategies in 1080/09638280500386569.
rhythmic sensorimotor tasks: phase vs period correction. Biol. Cybern. 79, 241–250. Wittwer, J.E., Webster, K.E., Hill, K., 2013. Music and metronome cues produce different
https://doi.org/10.1007/s004220050474. effects on gait spatiotemporal measures but not gait variability in healthy older
Thaut, M.H., Kenyon, G.P., Schauer, M.L., McIntosh, G.C., 1999a. The connection be- adults. Gait Posture 37, 219–222. https://doi.org/10.1016/j.gaitpost.2012.07.006.
tween rhythmicity and brain function. IEEE Eng. Med. Biol. Mag. 18, 101–108. Wu, T., Hallett, M., 2013. The cerebellum in Parkinson’s disease. Brain 136(Pt 3,
Thaut, M.H., Miltner, R., Lange, H.W., Hurt, C.P., Hoemberg, V., 1999b. Velocity mod- 696–709. https://doi.org/10.1093/brain/aws360.
ulation and rhythmic synchronization of gait in Huntington’s disease. Mov. Disord. Wu, T., Wang, L., Chen, Y., Zhao, C., Li, K., Chan, P., 2009. Changes of functional con-
14, 808–819. https://doi.org/10.1002/1531-8257(199909)14:5<808::AID- nectivity of the motor network in the resting state in Parkinson’s disease. Neurosci.
MDS1014>3.0.CO;2-J. Lett. 460, 6–10. https://doi.org/10.1016/j.neulet.2009.05.046.
Thaut, M.H., McIntosh, K.W., McIntosh, G.C., Hoemberg, V., 2001. Auditory rhythmicity Yeterian, Pandya, 1998. Corticostriatal connections of the superior temporal region in
enhances movement and speech motor control in patients with Parkinson’s disease. rhesus monkeys. J. Comp. Neurol. 399, 384–402.
Funct. Neurol. 163–172. Zatorre, R.J., Chen, J.L., Penhune, V.B., 2007. When the brain plays music: auditor-
Thaut, M., Trimarchi, P., Parsons, L., 2014. Human brain basis of musical rhythm per- y–motor interactions in music perception and production. Nat. Rev. Neurosci. 8,
ception: common and distinct neural substrates for meter, tempo, and pattern. Brain 547–558. https://doi.org/10.1038/nrn2152.

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