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From Eckart Altenmüller and Gottfried Schlaug, Apollo's gift: new aspects of neurologic music therapy.
In: Eckart Altenmüller, Stanley Finger and François Boller, editors, Progress in Brain Research, Vol. 217,
Amsterdam: Elsevier, 2015, pp. 237-252.
ISBN: 978-0-444-63551-8
© Copyright 2015 Elsevier B.V.
Elsevier
Provided for non
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commercial research and educational use only.
Not for reproduction, distribution or com
mercial use.
CHAPTER
Apollo’s gift: new aspects
of neurologic music
therapy 12
Eckart Altenm€
uller*, Gottfried Schlaug
†,1
*Institute of Music Physiology and Musicians’ Medicine (IMMM), University of Music, Drama and
Media, Hanover, Lower Saxony, Germany
†
Department of Neurology, Music and Neuroimaging Laboratory, and Neuroimaging, Stroke
Recovery Laboratories, Division of Cerebrovascular Disease, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA, USA
1
Corresponding author: Tel.: +1-617-6328912; Fax: +1-617-6328920,
e-mail address: gschlaug@bidmc.harvard.edu
Abstract
Music listening and music making activities are powerful tools to engage multisensory and
motor networks, induce changes within these networks, and foster links between distant,
but functionally related brain regions with continued and life-long musical practice. These
multimodal effects of music together with music’s ability to tap into the emotion and reward
system in the brain can be used to facilitate and enhance therapeutic approaches geared toward
rehabilitating and restoring neurological dysfunctions and impairments of an acquired or con-
genital brain disorder. In this article, we review plastic changes in functional networks and
structural components of the brain in response to short- and long-term music listening and mu-
sic making activities. The specific influence of music on the developing brain is emphasized
and possible transfer effects on emotional and cognitive processes are discussed. Furthermore,
we present data on the potential of using musical tools and activities to support and facilitate
neurorehabilitation. We will focus on interventions such as melodic intonation therapy and
music-supported motor rehabilitation to showcase the effects of neurologic music therapies
and discuss their underlying neural mechanisms.
Keywords
brain plasticity, melodic intonation therapy, music-supported training, neurologic music
therapy, neurorehabilitation
1MUSIC AS A DRIVER OF BRAIN PLASTICITY
Apollo’s gift, music, is one of the richest human emotional, sensory-motor, and cog-
nitive experiences. It involves listening, watching, feeling, moving and coordinating,
remembering, and expecting musical elements. It is frequently accompanied by strong
Progress in Brain Research, Volume 217, ISSN 0079-6123, http://dx.doi.org/10.1016/bs.pbr.2014.11.029
©2015 Elsevier B.V. All rights reserved.
237
Author's personal copy
emotions resulting in joy, happiness, and bittersweet sadness or even in overwhelming
bodily reactions like tears in the eyes or shivers down the spine. A large number of
cortical and subcortical brain regions are involved in music listening and music
making activities (for reviews see Altenm€
uller and McPherson, 2007; Tramo, 2001).
Primary and secondary regions in the cerebral cortex are critical for any conscious
perception of sensory information, be it auditory, visual, or somatosensory. However,
music also influences and changes activity in multisensory and motor integration
regions in frontal, parietal, and temporo-occipital brain regions. The frontal lobe is
involved in the guidance of attention, in planning and motor preparation, in integr ating
auditory and motor information, and in specific human skills such as imitation and
empathy. The two latter play an important role in the acquisition of musical skills
and emotional expressiveness. Multisensory integration regions in the parietal lobe
and temporo-occipital areas integrate different sensory inputs from the auditory,
visual, and somatosensory system into a combined sensory impression; it is this mul-
tisensory brain representation, which constitutes the typical musical experience. The
cerebellum is another important part of the brain that plays a critical role in musical
experience. It is important for motor coordination, but it also plays an important role in
various cognitive tasks especially when they include demands on timing. Typically,
the cerebellum is activated in rhythm processing, or tapping in synchrony with an
external pacemaker such as a metronome. Finally, the emotional network (comprising
the basis and the inner surfaces of the two frontal lobes, the cingulate gyrus and brain
structures in the evolutionarily old parts of the brain such as the amygdala, the hippo-
campus, and the midbrain) is crucial for the emotional perception of music and there-
fore for an individual’s motivation to listen to or to engage in any musical activity.
The brain is a highly dynamically organized structure that changes and adapts as a
result of activities and demands imposed upon it by the environment. Musical activ-
ity has proven to be a powerful stimulus for this kind of brain adaptation, or brain
plasticity (Wan and Schlaug, 2010). Effects of plasticity are not restricted to musical
prodigies, they occur in children learning to play a musical instrument (Hyde et al.,
2009) and in adult amateur musicians (Bangert and Altenm€
uller, 2003), albeit to a
lesser extent. Thus, with the main topic of our article in mind, we suggest that brain
plasticity induced through making music may produce manifold benefits. This holds
not only for changing and/or restoring compromised sensorimotor brain networks,
but also for influencing neurohormonal status as well as cognitive and emotional pro-
cesses in healthy and neurologically diseased/disordered individuals. Thus, various
sensory-motor, coordinative, or emotional disabilities can be improved with music-
supported therapy (MST).
This chapter briefly reviews the literature on music-induced brain plasticity, its
underlying mechanisms, and the impact that music has on emotion and neurohor-
mones. Subsequently, we will demonstrate transfer effects of music exposure and
music making to other cognitive and emotional domains and finally show examples
of the potential of music making to support and facilitate neurorehabilitation.
Our intent is not to provide an exhaustive review, but to focus our chapter on
music-supported interventions geared toward improving the rehabilitation of speech-
and limb-motor impairments following brain injury.
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2SOME MECHANISMS OF MUSIC-INDUCED BRAIN
PLASTICITY
During the past decade, brain imaging has provided important insight into the enor-
mous capacity of the human brain to adapt to complex demands. These adaptations
are referred to as brain plasticity and do not only include the quality and extent of
functional connections of brain networks, but also fine structures of nervous tissue
and even the macroscopic gross structure of brain anatomy (Bangert and Schlaug,
2006). Brain plasticity is best observed in complex tasks, including, for example,
temporospatially precise movements with high behavioral relevance. These behav-
iors are usually accompanied by emotional arousal and motivational activation of the
reward system. Furthermore, plastic changes are more pronounced when the specific
activities have started before puberty and require intense training. Obviously, con-
tinued musical activities throughout the life of a musician provide an ideal setup for
brain plasticity to occur. It is therefore not surprising that the most dramatic effects of
brain plasticity have been demonstrated in professional musicians (for a classic re-
view see M€
unte et al., 2002; for more recent reviews Wan and Schlaug, 2010; and
Altenm€
uller and Schlaug, 2012, 2013).
Our understanding of the molecular and cellular mechanisms underlying these
adaptations is far from complete. Brain plasticity may occur on different time scales.
For example, the efficiency and size of synapses may be modified in a time window
of seconds to minutes, the growth of new synapses and dendrites may require hours
to days. Other changes require up to several weeks. They include an increase in gray
matter density, reflecting either an enlargement of neurons, a change in synaptic den-
sity, more support structures such as capillaries and glial cells or a reduced rate of
physiological cell death (apoptosis). White-matter density also changes as a conse-
quence of musical training. This effect seems to be primarily due to an enlargement
of myelin cells: The myelin cells, wrapped around the nerve fibers (axons) are con-
tributing essentially to the velocity of the electrical impulses traveling along the
nerve fiber tracts. Under conditions requiring rapid information transfer and high
temporal precision, these myelin cells are growing, and, as a consequence, nerve con-
duction velocity will increase. The axons within these myelin sheaths can potentially
sprout and form more and new connections particularly between the nodal cortical
points that are connected by white tracts (for a recent publication on this see Wan
et al., 2014). Finally, brain regions involved in specific tasks may also be enlarged
after long-term training due to the growth of structures supporting the nervous func-
tion, for example, blood vessels/capillaries that are necessary for the oxygen and glu-
cose transportation sustaining nervous function or glial cells as supporters of the
local homeostasis.
Comparison of the brain anatomy of skilled musicians with that of nonmusicians
shows that prolonged instrumental practice leads to an enlargement of the hand area
in the motor cortex (Amunts et al., 1997). Furthermore, Gaser and Schlaug (2003)
could demonstrate enhancement of gray matter density in cortical sensory-motor
2392 Some mechanisms of music-induced brain plasticity
Author's personal copy
regions, auditory regions, the left dorsolateral prefrontal cortex, and in the cerebel-
lum in professional instrumentalists as compared to nonmusicians and amateurs. In-
terestingly, these plastic adaptations depend on critical periods: musicians, who start
early, before the age of seven do not display these structural adaptations of the brain
at least in the sensory-motor cortices and the callosal fibers, however, they seem to
have an “early optimized network,” which allows superior performance of motor
tasks without enlarged anatomical structures (Steele et al., 2013;Vaquero et al.,
2014). In contrast, relatively late starters, after age seven do show the above-
mentioned structural adaptations accounting for the effects observed in many mor-
phological brain imaging studies (e.g., Bangert and Schlaug, 2006; Ga
¨rtner et al.,
2013).
With respect to the larger callosal body in musicians, it seems plausible to assume
that the high demands on coordination between the two hands, and the rapid ex-
change of information may either stimulate the nerve fiber growth—the myelination
of nerve fibers that determines the velocity of nerve conduction—or prevent the
physiological loss of nerve tissue during the typical pruning processes of adolescence
or during aging. These between-group differences in the midsagittal size of the cor-
pus callosum were confirmed in a longitudinal study comparing a group of children
learning to play musical instruments versus a group of children without instrumental
music experience (Hyde et al., 2009).
Halwani et al. (2011) recently showed another impressive adaptation of white-
matter structures. They reported differences in macrostructure and microstructure
of the arcuate fasciculus (AF)—a prominent white-matter tract connecting temporal
and frontal brain regions—between singers, instrumentalists, and nonmusicians.
Both groups of musicians had higher tract volumes in the right dorsal and ventral
tracts compared to nonmusicians, but did not show a significant difference between
each other. Singers had higher tract volume and different microstructures of the tract
on the left side when compared to instrumental musicians and nonmusicians. This
suggests that the right-hemisphere AF might show a more general effect of music
making, while the left-hemisphere AF has a stronger response to the specific aspects
of vocal-motor training and control that singers engage in. Microstructural parame-
ters (i.e., fractional anisotropy) of the left dorsal branch of the arcuate fasciculus
correlated with the number of years of participants’ vocal training, suggesting that
long-term vocal-motor training might not only lead to an increase in volume, but also
to an increase in microstructural complexity of specific white-matter tracts consti-
tuting the so-called aural–oral loop and connecting regions that are fundamental
to sound perception, production, and its feed forward and feedback control. Simi-
larly, Bengtsson et al. (2005) and recently Rueber et al. (2013) have found structural
differences in the corticospinal tract, particularly in the posterior limb of the internal
capsule, between musicians and nonmusicians as well as within musicians groups
(keyboard players compared to string players). Between group differences were re-
lated to measures of training intensity as well as to the specific requirements of the
instruments played. It is worth to mention that instrumental training does not only
affect cortical regions, but subcortical structures also seem to show adaptation.
240 CHAPTER 12 Apollo’s gift
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For example, professional musicians in comparison to matched nonmusicians, seem
to have a larger cerebellar volume or cerebellar gray matter (Gaser and Schlaug,
2003; Hutchinson et al., 2003). The cerebellum plays a role in the precise timing,
accuracy, and coordination of motor actions, which is an important aspect of instru-
mental music activities.
In summary, instrumental music training, particularly when it starts at a young
age, leads to plastic adaptations of various cortical and subcortical brain structures
and functional networks. These changes can also include enlarged cortical represen-
tations of, for example, specific fingers or specific sounds or timbre of sounds (e.g., a
string timbre vs. a brass timbre) within existing brain structures.
3THE ROLE OF MUSIC-INDUCED EMOTIONS FOR BRAIN
PLASTICITY
An intriguing question is why music is such a powerful driver of beneficial brain
plasticity. This brings us to the specific motivational and emotional role of musical
experience. Emotional responses to music are often cited when people describe why
they value music and why they ascribe certain effects of music on health. Music is
known to have a wide range of physiological effects on the human body including,
for example, changes in heart rate, respiration, blood pressure, skin conductivity,
skin temperature, muscle tension, and biochemical responses (for a review see
Hodges, 2010; Kreutz et al., 2012).
Joyful musical behaviors, for example, learning to play a musical instrument or to
sing is characterized by curiosity, stamina, and the ability to strive for rewarding ex-
periences in future. This results in incentive goal directed activities over prolonged
time periods, which are mainly mediated by the transmitter substance dopamine.
Most nerve cells sensitive to this neurotransmitter are found in a small part of the
brain, which is localized behind the basis of the frontal cortex, the so-called meso-
limbic system, an important part of the “emotional” brain. Dopamine plays a dom-
inant role in the neurobiology of reward, learning, and addiction. Virtually all drugs
of abuse, including heroin, alcohol, cocaine, and nicotine activate dopaminergic sys-
tems. So-called natural rewards such as musical experiences and other positive social
interactions likewise activate dopaminergic neurons and are powerful aids to atten-
tion and learning (Keitz et al., 2003). There is ample evidence that the sensitivity to
dopamine in the mesolimbic brain regions is largely genetically determined resulting
in the enormous variability in reward-dependent behavior. The genetic
“polymorphism” of dopaminergic response explains the different motivational
drives we observe in children with a similar social and educational background. It
is intriguing that there is a strong link of dopaminergic activity to learning and mem-
ory, which in turn promote plastic adaptations in brain areas involved in the tasks to
be learned.
Serotonin is another neurotransmitter important for music-induced brain plastic-
ity. It is commonly associated with feelings of satisfaction from expected outcomes,
2413 The role of music-induced emotions for brain plasticity
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whereas dopamine is associated with feelings of pleasure based on novelty or new-
ness. In a study of neurochemical responses to pleasant and unpleasant music, sero-
tonin levels were significantly higher when subjects were exposed to music they
found pleasing (Evers and Suhr, 2000). In another study with subjects exposed to
pleasing music, functional and effective connectivity analyses showed that listening
to music strongly modulated activity in a network of mesolimbic structures involved
in reward processing including the dopaminergic nucleus accumbens and the ventral
tegmental area, as well as the hypothalamus and insula. This network is believed to
be involved in regulating autonomic and physiological responses to rewarding and
emotional stimuli (Menon and Levitin, 2005).
Blood and Zatorre (2001) determined changes in regional cerebral blood flow
(rCBF) with PET technology during intense emotional experiences involving sensa-
tions such as goose bumps or shivers down the spine whilst listening to music. Each
participant listened to a piece of their own favorite music to which they usually had a
chill experience. Increasing chill intensity correlated with rCBF decrease in
the amygdala as well as the anterior hippocampal formation. An increase in rCBF
correlating with increasing chill intensity was observed in the ventral striatum,
the midbrain, the anterior insula, the anterior cingulate cortex, and the orbitofrontal
cortex: Again, these latter brain regions are related to reward and positive emotional
valence.
In a newer study by the same group, the neurochemical specificity of [(11)C]
raclo-pride PET scanning was used to assess dopamine release on the basis of the
competition between endogenous dopamine and [11C]raclopride for binding to do-
pamine D2 receptors (Salimpoor et al., 2011). They combined dopamine-release
measurements with psychophysiological measures of autonomic nervous system ac-
tivity during listening to intensely pleasurable music and found endogenous dopa-
mine release in the striatum at peak emotional arousal during music listening. To
examine the time course of dopamine release, the authors used functional magnetic
resonance imaging (fMRI) with the same stimuli and listeners, and found a func-
tional dissociation: the caudate was more involved during the anticipation and the
nucleus accumbens was more involved during the experience of peak emotional re-
sponses to music. These results indicate that intense pleasure in response to music
can lead to dopamine release in the striatal system. Notably, the anticipation of an
abstract reward can result in dopamine release in an anatomical pathway distinct
from that associated with the peak pleasure itself. Such results may well help to ex-
plain why music is of such high value across all human societies. As stated above,
dopaminergic activation regulates and heightens arousal, motivation and supports
memory formation in the episodic and the procedural memory (Karabanov et al.,
2010) and thereby will contribute to memorization of auditory stimuli producing
such strong emotional responses. In a very recent study, the authors could even dem-
onstrate that the degree of activation and connectivity in a network comprising the
nucleus accumbens, auditory cortices, amygdala, and ventromedial frontal cortex
predicted the amount of money, subjects were willing to spend in an auction para-
digm (Salimpoor et al., 2013).
242 CHAPTER 12 Apollo’s gift
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Taken together, these powerful music-induced modulations of neurohormonal
status may not only account for pleasurable experiences but may also play a role
in neurologic music therapy.
4FACILITATING RECOVERY FROM NONFLUENT APHASIA
THROUGH A FORM OF SINGING
The ability to sing in humans is evident from infancy, and does not depend on formal
vocal training but can be enhanced by training. Given the behavioral similarities be-
tween singing and speaking, as well as the shared and distinct neural correlates of
both, researchers have begun to examine whether forms of singing can be used to
treat some of the speech-motor abnormalities associated with various neurological
conditions (Wan et al., 2010).
Aphasia is a common and devastating complication of stroke or other brain in-
juries that results in the loss of ability to produce and/or comprehend language. It
has been estimated that between 24% and 52% of acute stroke patients have some
form of aphasia if tested within 7 days of their stroke; 12% of survivors still have
significant aphasia at 6 months after stroke (Wade et al., 1976). The nature and se-
verity of language dysfunction depends on the location and extent of the brain lesion.
Accordingly, aphasia can be classified broadly into fluent or nonfluent. Fluent apha-
sia often results from a lesion involving the posterior superior temporal lobe known
as Wernicke’s area. Patients who are fluent exhibit articulated speech with relatively
normal utterance length. However, their speech may be completely meaningless to
the listener and littered with jargon. Furthermore, it may contain violations to syn-
tactic and grammatical rules. These patients also have severe speech comprehension
deficits. In contrast, nonfluent aphasia results most commonly from a lesion in the
left frontal lobe, involving the left posterior inferior frontal region known as Broca’s
area. Patients who are nonfluent tend to have relatively intact comprehension for
conversational speech, but have marked impairments in articulation and speech
production.
The general consensus is that there are two routes to recovery from aphasia. In
patients with small lesions in the left hemisphere, there tends to be recruitment of
both left-hemispheric, perilesional cortices with variable involvement of right-
hemispheric homologous regions during the recovery process (Heiss and Thiel,
2006; Heiss et al., 1999; Hillis, 2007; Rosen et al., 2000). In patients with large
left-hemispheric lesions involving language-related regions of the frontotemporal
lobes, the only path to recovery may be through recruitment of homologous language
and speech-motor regions in the right hemisphere (Geschwind, 1971; Schlaug et al.,
2008). It has been suggested that recovery via the right hemisphere may be less ef-
ficient than recovery via the left hemisphere (Hillis, 2007), possibly because patients
with relatively large left-hemispheric lesions that encompass all of the relevant
speech-motor regions of the left hemisphere are generally more impaired and recover
to a lesser degree than patients with smaller left-hemisphere lesions. Nevertheless,
2434 Facilitating recovery from nonfluent aphasia through a form of singing
Author's personal copy
activation of right-hemispheric regions during speech/language fMRI tasks has been
reported in patients with aphasia, irrespective of their lesion size (Rosen et al., 2000).
For patients with large lesions that cover the language-relevant regions on the left,
therapies that specifically engage or stimulate the homologous right-hemispheric re-
gions have the potential to facilitate the language recovery process beyond the lim-
itations of natural recovery (Gerstman, 1964; Keith and Aronson, 1975). Based on
clinical observations of patients with severe nonfluent aphasia and their ability to
sing lyrics better than they can speak the same words (Albert et al., 1973;
Schlaug et al., 2010; Sparks and Holland, 1976), an intonation-based therapy called
Melodic Intonation Therapy (MIT) that would emphasize melody and contour and
engage a sensorimotor network of articulation on the unaffected hemisphere through
rhythmic tapping was developed (Albert et al., 1973; Schlaug et al., 2010). The two
unique components of MIT are first the intonation of words and simple phrases using
a melodic contour that follows the prosody of speech, and second the rhythmic tap-
ping of the left hand that accompanies the production of each syllable and serves as a
catalyst for fluency.
To date, studies using MIT have produced positive outcomes in patients with
nonfluent aphasia. These outcomes range from improvements on the Boston Diag-
nostic Aphasia Examination (BDAE; Goodglass and Kaplan, 1983), to improve-
ments in articulation and phrase production (Bonakdarpour et al., 2000; Wilson
et al., 2006) after treatment. The effectiveness of this intervention is further demon-
strated in a recent study that examined transfer of language skills to untrained con-
texts. Schlaug et al. (2008) compared the effects of MIT with a control intervention
(speech repetition) on picture naming performance and measures of propositional
speech. After 40 daily sessions, both therapy techniques resulted in significant im-
provement on all outcome measures, but the extent of this improvement was far
greater for the patient who underwent MIT compared to the one who underwent
the control therapy.
The therapeutic effect of MIT is also evident in neuroimaging studies that show
reorganization of brain functions. MIT resulted in increased activation in a right-
hemisphere network involving the premotor, inferior frontal, and temporal lobes
(Schlaug et al., 2008), as well as increased fiber number and volume of the arcuate
fasciculus in the right hemisphere (Schlaug et al., 2009; Wan et al., 2014). These
findings demonstrate that intensive experimental therapies such as MIT—when ap-
plied over a longer period of time in chronic stroke patients—can induce functional
and structural brain changes in a right-hemisphere vocal-motor network, and these
changes are related to speech output improvements (Wan et al., 2014).
The mechanisms that are underlying the recovery-enhancing effects of MIT are
not completely clear. However, it has been argued that we suggest that there are four
possible mechanisms by which MIT’s therapeutic effect is achieved (for details, see
Schlaug et al., 2008): (1) reduction of speed to approximately one syllable/sec. which
may specifically engage right-hemisphere perceptual and perception–action cou-
pling on the right hemisphere, as the right hemisphere has been shown to integrate
sensory information over a larger time window than the left (Abrams et al., 2008;
244 CHAPTER 12 Apollo’s gift
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Poeppel, 2003); (2) syllable lengthening that isolates/emphasizes individual pho-
nemes even as they remain part of the continuously voiced words/phrases; and (3)
“chunking” that not only combines prosodic information with meaningful content
to facilitate production of longer, more fluent phrases, but has also been shown to
lead to more right- than left-hemisphere activation in healthy subjects (Meyer
et al., 2002; Ozdemir et al., 2006; Zatorre and Belin, 2001). Given that, patients with
right-hemisphere lesions have greater difficulty with global processing tasks (e.g.,
melody and contour processing) than those with left-hemisphere lesions (Peretz,
1990; Schuppert et al., 2000), it is possible that the melodic element of MIT does,
indeed engage the right hemisphere, particularly the right temporal lobe, more than
therapies that do not make use of tonal information or melodic contour, and again
intervention that would integrate information over a larger timescale favoring right
over left-hemispheric processing (Poeppel, 2003). The fourth mechanism—Left-
hand tapping (one tap/syllable,one syllable/sec.)—is likely to play an important role
in engaging a right-hemispheric, sensorimotor network capable of providing an im-
pulse for verbal production in much the same way that a metronome has been shown
to serve as a “pacemaker” when rhythmic motor activities prime and/or entrain sen-
sorimotor networks (Thaut and Abiru, 2010; Thaut et al., 1999). In addition, research
suggesting that hand movements and articulatory movements may share neural cor-
relates (Gentilucci et al., 2000; Meister et al., 2003; Tokimura et al., 1996; Uozumi
et al., 2004) further supports the notion that hand tapping is critically important for
facilitating the coupling of sounds to orofacial and articulatory actions (Lahav et al.,
2007). Since concurrent speech and hand use occurs in daily life, and gestures are
frequently used to emphasize/accompany important and/or elusive concepts in
speech, rhythmic hand movements, in synchrony with articulatory movements,
may have similarly beneficial effects on speech production and in particular in
relearning of speech-motor functions after a stroke.
5MUSIC-SUPPORTED MOTOR THERAPY IN STROKE
PATIENTS
MST in the rehabilitation of fine motor hand skills was first systematically investi-
gated by Schneider et al. (2007). Patients were encouraged to play melodies with the
paretic hand on a piano, or to tap with the paretic arm on eight electronic drum pads
that emitted piano tones. It was demonstrated that these patients regained faster their
motor abilities, and improved in timing, precision, and smoothness of fine motor
skills. Along with fine motor recovery, an increase in neuronal connectivity between
sensory-motor and auditory regions was demonstrated by means of EEG-coherence
measures (Altenm€
uller et al., 2009; Rojo et al., 2012; Schneider et al., 2010).
Therefore, establishing an audio-sensory-motor co-representation may support the
rehabilitation process (see Fig. 1). This notion is corroborated by findings in a patient
who underwent music-supported training 20 months after suffering a stroke. Along
with clinical improvement, fMRI follow up provided evidence for the establishment
2455 Music-supported motor therapy in stroke patients
Author's personal copy
of an auditory-sensory-motor network due to the training procedure (Rojo et al.,
2012). Recently, in a larger group of 20 stroke patients, changes in motor cortex ex-
citability following a 4 weeks intervention were demonstrated with the transcranial
magnetic stimulation technique. These changes were accompanied with marked im-
provements of fine motor skills (Amengual et al., 2013).
Music-supported training is undoubtedly efficient and seems to be even more
helpful than functional motor training using no auditory feedback, but otherwise sim-
ilar fine motor training. A randomized prospective study comprising all three groups
is presently under the way and will clarify the differential effects of functional motor
training and music-supported training. With respect to the underlying mechanisms, a
number of open questions still remain. First, the role of motivational factors must
be clarified. From the patients’ informal descriptions of their experience with the
music-supported training, it appears that this was highly enjoyable and a highlight
of their rehabilitation process. Thus, motivational and emotional factors might have
contributed to the success of the training program. Furthermore, according to a study
by Sa
¨rka
¨m€
o et al. (2008), music listening activates a widespread bilateral network of
brain regions related to attention, semantic processing, memory, motor functions,
F3 Fz F4
FC4
C4
CP4
P4Pz
CPz
Cz
FCz
P3
CP3
C3
FC3
MG CG CGMG
Affected extremit
y
Nonaffected extremit
y
<0.05 <0.15
<0.1 <0.2
FIGURE 1
Topographic task-related coherence maps for the Music group (MG) compared to the control
group (CG) during self-paced arm movements for the drum pad condition in the beta band
(18–22 Hz). Statistically significant increases in task-related coherence during the motor
performance after 3 weeks and 15 sessions of music-supported therapy on sonified drum
pads are displayed.
From Altenm €
uller and Schlaug (2013) with permission.
246 CHAPTER 12 Apollo’s gift
Author's personal copy
and emotional processing. Sa
¨rka
¨m€
o and colleagues showed that music exposure sig-
nificantly enhances cognitive functioning in the domains of verbal memory and fo-
cused attention in stroke patients. The music group also experienced less depressed
mood than the control groups. These mechanisms may also hold true for the music-
supported training we applied.
Another issue is related to the auditory feedback mechanisms. Up to now, it has
not been clear whether any auditory feedback (e.g., simple beep tones) would have a
similar effect on fine motor rehabilitation or whether explicit musical parameters
such as a sophisticated pitch and time structure are prerequisites for the success
of the training. This has to be addressed in a study comparing the effects of musical
feedback compared to simple acoustic feedback. With respect to the latter, according
to a study by Thaut et al. (2002), simple rhythmic cueing with a metronome signif-
icantly improves the spatiotemporal precision of reaching movements in stroke
patients.
Furthermore, it is not clear, whether timing regularity and predictability is crucial
for the beneficial effect of MST using key-board playing or tapping on drumpads.
Although it has been argued that the effectiveness of this therapy relies on the fact that
the patient’s brain receives a time-locked auditory feedback with each movement, new
results challenge this viewpoint. In a recent study, 15 patients in early stroke rehabil-
itation with no previous musical background learned to play simple finger exercises
and familiar children’s songs on the piano. The participants were assigned to one of
two groups: in the normal group, the keyboard emitted a tone immediately at key-
stroke, in the delay group, the tone was delayed by a random time interval between
100 and 600 ms. To assess recovery, we performed standard clinical tests such as
the nine-hole-pegboard test and index finger tapping speed and regularity. Surpris-
ingly, patients in the delay group improved more in the nine-hole-pegboard test,
whereas patients in the normal group did not. In finger tapping rate and regularity
both groups showed similar marked improvements. The normal group showed re-
duced depression whereas the delay group did not (van Vugt et al., 2014). Here, we
conclude that music therapy on a randomly delayed keyboard can improve motor
recovery after stroke. We hypothesize that the patients in the delayed feedback group
implicitly learn to be independent of the auditory feedback and therefore outperform
those in the normal condition.
Finally, the stability of improvements needs to be assessed in further studies, and
the length and number of training sessions might be manipulated in future research.
Additionally, the effect of training in chronic patients suffering from motor impair-
ments following a stroke for more than a year will be assessed.
6CONCLUSIONS
Emerging research over the past decade has shown that long-term music training and
the associated sensorimotor skill learning can be a strong stimulant for neuroplastic
changes in the developing as well as in the adult brain, affecting both white and gray
2476 Conclusions
Author's personal copy
matter as well as cortical and subcortical structures. Making music including singing
and dancing leads to a strong coupling of perception and action mediated by sensory,
motor, and multimodal brain regions and affects either in a top-down or bottom-up
fashion important relay stations in the brainstem and thalamus. Furthermore, listen-
ing to music and making music provokes motions and emotions, increases between-
subject communications and interactions and—mediated via neurohormons such as
serotonin and dopamine—is experienced as joyous and rewarding through activity
changes in amygdala, ventral striatum, and other components of the limbic system.
Making music makes rehabilitation more enjoyable and can remediate impaired neu-
ral processes or neural connections by engaging and linking brain regions with each
other that might otherwise not be linked together.
As other experimental interventions, music-based experimental interventions
need to be grounded on a neurobiological understanding of how and why particular
brain systems could be affected. The efficacy of these experimental interventions
should be assessed quantitatively and in an unbiased way. A neuroscientific basis
for music-based interventions and data derived from randomized clinical trials are
important steps in establishing neurologically based music therapies that might have
the power to enhance brain recovery processes, ameliorate the effects of develop-
mental brain disorders, and neuroplasticity in general.
ACKNOWLEDGMENTS
G. S. gratefully acknowledges support from NIH (1RO1 DC008796, 3R01DC008796-02S1,
R01 DC009823-01), the family of Rosalyn and Richard Slifka, and the Matina R. Proctor
Foundation.
Parts of this Review Article are containing an updated version of a previous review, which
appeared 2013 in the Journal “Music and Medicine.”
REFERENCES
Abrams, D.A., Nicol, T., Zecker, S., Kraus, N., 2008. Right-hemisphere auditory cortex is
dominant for coding syllable patterns in speech. J. Neurosci. 28, 3958–3965.
Albert, M.L., Sparks, R.W., Helm, N.A., 1973. Melodic intonation therapy for aphasia. Arch.
Neurol. 29, 130–131.
Altenm€
uller, E., McPherson, G., 2007. Motor learning and instrumental training. In: Gruhn, F.R.
(Ed.), Neurosciences in Music Pedagogy. Nova Science Publisher, New York, NY,
pp. 145–155.
Altenm€
uller, E., Schlaug, G., 2012. Music, brain, and health: exploring biological foundations
of music’s health effects. In: MacDonald, R., Kreutz, G., Mitchell, L. (Eds.), Music,
Health, and Wellbeing. Oxford University Press, Oxford, pp. 12–24.
Altenm€
uller, E., Schlaug, G., 2013. Neurobiological aspects of neurologic music therapy.
Music Med. 5, 210–216.
248 CHAPTER 12 Apollo’s gift
Author's personal copy
Altenm€
uller, E., Schneider, S., Marco-Pallares, P.W., M€
unte, T.F., 2009. Neural reorganiza-
tion underlies improvement in stroke induced motor dysfunction by music supported ther-
apy. Ann. N. Y. Acad. Sci. 1169, 395–405.
Amengual, J.L., Rojo, N., Veciana de las Heras, M., Marco-Pallare
´s, J., Grau, J., Schneider, S.,
Vaquero, L., Juncadella, M., Montero, J., Mohammadi, B., Rubio, F., Rueda, N.,
Duarte, E., Grau, E., Altenm€
uller, E., M€
unte, T.F., Rodrı
´guez-Fornells, A., 2013. Senso-
rimotor plasticity after music-supported therapy in chronic stroke patients revealed by
transcranial magnetic stimulation. PLoS One 8, e61883. http://dx.doi.org/10.1371/jour-
nal.pone.0061883.
Amunts, K., Schlaug, G., Ja
¨ncke, L., Steinmetz, H., Schleicher, A., Dabringhaus, A., Zilles, K.,
1997. Motor cortex and hand motor skills: structural compliance in the human brain. Hum.
Brain Mapp. 5, 206–215.
Bangert, M., Altenm€
uller, E., 2003. Mapping perception to action in piano practice: a longi-
tudinal DC-EEG-study. BMC Neurosci. 4, 26–36.
Bangert, M., Schlaug, G., 2006. Specialization of the spezialized in features of external brain
morphology. Eur. J. Neurosci. 24, 1832–1834.
Bengtsson, S.L., Nagy, Z., Skare, S., Forsman, L., Forssberg, H., Ullen, F., 2005. Extensive
piano practicing has regionally specific effects on white matter development. Nat. Neu-
rosci. 8, 1148–1150.
Blood, A.J., Zatorre, R.J., 2001. Intensely pleasurable responses to music correlate with activity
in brain regions implicated in reward and emotion. Proc. Natl. Acad. Sci. U. S. A.
198, 11818–11823.
Bonakdarpour, B., Eftekharzadeh, A., Ashayeri, H., 2000. Preliminary report on the effects of
melodic intonation therapy in the rehabilitation of Persian aphasic patients. Iran. J. Med.
Sci. 25, 156–160.
Evers, S., Suhr, B., 2000. Changes of the neurotransmitter serotonin but not of hormones dur-
ing short time music perception. Eur. Arch. Psychiatry Clin. Neurosci. 250, 144–147.
Ga
¨rtner, H., Minnerop, M., Pieperhoff, P., Schleicher, A., Zilles, K., Altenm€
uller, E.,
Amunts, K., 2013. Brain morphometry shows effects of long-term musical practice in
middle-aged keyboard players. Front. Psychol. 4, 636. http://dx.doi.org/10.3389/
fpsyg.2013.00636.
Gaser, C., Schlaug, G., 2003. Brain structures differ between musicians and non-musicians.
J. Neurosci. 23, 9240–9245.
Gentilucci, M., Benuzzi, F., Bertolani, L., Daprati, E., Gangitano, M., 2000. Language and
motor control. Exp. Brain Res. 133, 468–490.
Gerstman, H.L., 1964. A case of aphasia. J. Speech Hear. Disord. 29, 89–91.
Geschwind, N., 1971. Current concepts: aphasia. N. Engl. J. Med. 284, 654–656.
Goodglass, H., Kaplan, E., 1983. Boston Diagnostic Aphasia Examination, second ed. Lea &
Febiger, Philadelphia, PA.
Halwani, G.F., Loui, P., R€
uber, T., Schlaug, G., 2011. Effects of practice and experience on the
arcuate fasciculus: comparing singers, instrumentalists, and non-musicians. Front. Psy-
chol. 2, 156. http://dx.doi.org/10.3389/fpsyg.2011.001561.
Heiss, W.D., Thiel, A., 2006. A proposed regional hierarchy in recovery of post-stroke apha-
sia. Brain Lang. 98, 118–123.
Heiss, W.D., Kessler, J., Thiel, A., Ghaemi, M., Karbe, H., 1999. Differential capacity of left and
right hemispheric areas for compensation of poststroke aphasia. Ann. Neurol. 45, 430–438.
Hillis, A.E., 2007. Aphasia: progress in the last quarter of a century. Neurology 69, 200–213.
249References
Author's personal copy
Hodges, D.A., 2010. Psychophysiological measures. In: Juslin, P.N., Sloboda, J.A. (Eds.),
Handbook of Music and Emotion. Oxford University Press, Oxford, pp. 279–311.
Hutchinson, S., Lee, L.H.L., Gaab, N., Schlaug, G., 2003. Cerebellar volume: gender and mu-
sicianship effects. Cereb. Cortex 13, 943–949.
Hyde, K.L., Lerch, J., Norton, A., Forgeard, M., Winner, E., Evans, A.C., Schlaug, G., 2009.
Musical training shapes structural brain development. J. Neurosci. 29, 3019–3025.
Karabanov, A., Cervenka, S., de Manzano, O., Forssberg, H., Farde, L., Ulle
´n, F., 2010. Do-
pamine D2 receptor density in the limbic striatum is related to implicit but not explicit
movement sequence learning. Proc. Natl. Acad. Sci. 107, 7574–7579.
Keith, R.L., Aronson, A.E., 1975. Singing as therapy for apraxia of speech and aphasia: report
of a case. Brain Lang. 2, 483–488.
Keitz, M., Martin-Soelch, C., Leenders, K.L., 2003. Reward processing in the brain: a prereq-
uisite for movement preparation? Neural Plast. 1, 121–128.
Kreutz, G., Quiroga Murcia, C., Bongard, S., 2012. Psychoneuroendocrine research on music
and health. An overview. In: MacDonald, R., Kreutz, G., Mitchell, L. (Eds.), Music, Health
and Wellbeing. Oxford University Press, Oxford, pp. 457–476.
Lahav, A., Saltzman, E., Schlaug, G., 2007. Action representation of sound: audio-
motor recognition network while listening to newly acquired actions. J. Neurosci.
27, 308–314.
Meister, I.G., Boroojerdi, B., Foltys, H., Sparing, R., Huber, W., Topper, R., 2003. Motor cor-
tex hand area and speech: implications for the development of language.
Neuropsychologia 41, 401–406.
Menon, V., Levitin, D.J., 2005. The rewards of music listening: response and physiological
connectivity of the mesolimbic system. NeuroImage 28, 175–184.
Meyer, M., Alter, K., Friederici, A.D., Lohmann, G., von Cramon, D.Y., 2002. FMRI reveals
brain regions mediating slow prosodic modulations in spoken sentences. Hum. Brain
Mapp. 17, 73–88.
M€
unte, T.F., Altenm€
uller, E., Ja
¨ncke, L., 2002. The musician’s brain as a model of neuroplas-
ticity. Nat. Neurosci. 3, 473–478.
Ozdemir, E., Norton, A., Schlaug, G., 2006. Shared and distinct neural correlates of singing
and speaking. NeuroImage 33, 628–635.
Peretz, I., 1990. Processing of local and global musical information by unilateral brain-
damaged patients. Brain 113, 1185–1205.
Poeppel, D., 2003. The analysis of speech in different temporal integration windows: cerebral
lateralization as “asymmetric sampling in time” Speech Comm. 41, 245–255.
Rojo, N., Amengual, J., Juncadella, M., Rubio, F., Camara, E., Marco-Pallares, J.,
Schneider, S., Veciana, M., Montero, J., Mohammadi, B., Altenm€
uller, E., Grau, C.,
M€
unte, T.F., Rodriguez-Fornells, A., 2012. Music-supported therapy induces plasticity
in the sensorimotor cortex in chronic stroke: a single-case study using multimodal imaging
(fMRI-TMS). Brain Inj. 25, 787–793.
Rosen, H.J., Petersen, S.E., Linenweber, M.R., 2000. Neural correlates of recovery from apha-
sia after damage to left inferior frontal cortex. Neurology 55, 1883–1894.
Rueber, T., Lindenberg, R., Schlaug, G., 2013. Differential adaptation of descending motor
pathways in musicians. Cereb. Cortex http://dx.doi.org/10.1093/cercor/bht331[Epub
ahead of print].
Salimpoor, V.N., Benovoy, M., Larcher, K., Dagher, A., Zatorre, R.J., 2011. Anatomically
distinct dopamine release during anticipation and experience of peak emotion to music.
Nat. Neurosci. 14, 257–262.
250 CHAPTER 12 Apollo’s gift
Author's personal copy
Salimpoor, V.N., van den Bosch, I., Kovacevicm, N., McIntoshm, A.R., Dagher, A.,
Zatorre, R.J., 2013. Interactions between the nucleus accumbens and auditory cortices pre-
dict music reward value. Science 340, 216–219.
Sa
¨rka
¨m€
o, T., Tervaniemi, M., Laitinen, S., Forsblom, A., Soinila, S., Mikkonen, M., 2008.
Music listening enhances cognitive recovery and mood after middle Cerebral artery stroke.
Brain 131, 866–876.
Schlaug, G., Marchina, S., Norton, A., 2008. From singing to speaking: why patients with
Broca’s aphasia can sing and how that may lead to recovery of expressive language func-
tions. Music. Percept. 25, 315–323.
Schlaug, G., Marchina, S., Norton, A., 2009. Evidence for plasticity in white-matter tracts of
patients with chronic Broca’s aphasia undergoing intense intonation-based speech therapy.
Ann. N. Y. Acad. Sci. 1169, 385–394.
Schlaug, G., Norton, A., Marchina, S., Zipse, L., Wan, C.Y., 2010. From singing to speaking:
facilitating recovery from nonfluent aphasia. Future Neurol. 5, 657–665.
Schneider, S., Sch€
onle, P.W., Altenm€
uller, E., M€
unte, T.F., 2007. Using musical instruments
to improve motor skill recovery following a stroke. J. Neurol. 254, 1339–1346.
Schneider, S., M€
unte, T.F., Rodriguez-Fornells, A., Sailer, M., Altenm€
uller, E., 2010. Music
supported training is more efficient than functional motor training for recovery of fine mo-
tor skills in stroke patients. Music. Percept. 27, 271–280.
Schuppert, M., Munte, T.F., Wieringa, B.M., Altenmuller, E., 2000. Receptive amusia: evi-
dence for cross-hemispheric neural networks underlying music processing strategies.
Brain 123, 546–559.
Sparks, R.W., Holland, A.L., 1976. Method: melodic intonation therapy for aphasia. J. Speech
Hear. Disord. 41, 287–297.
Steele, C.J., Bailey, J.A., Zatorre, R.J., Penhune, V.B., 2013. Early musical training and white-
matter plasticity in the corpus callosum: evidence for a sensitive period. J. Neurosci.
33, 1282–1290.
Thaut, M.H., Abiru, M., 2010. Rhythmic auditory stimulation in rehabilitation of movement
disoders: a review of current research. Music. Percept. 27, 263–269.
Thaut, M.H., Kenyon, G.P., Schauer, M.L., McIntosh, G.C., 1999. The connection between
rhythmicity and brain function. IEEE Eng. Med. Biol. Mag. 18, 101–108.
Thaut, M.H., Kenyon, G.P., Hurt, C.P., McIntosh, G.C., Hoemberg, V., 2002. Kinematic op-
timization of spatiotemporal patterns in paretic arm training with stroke patients.
Neuropsychologia 40, 1073–1081.
Tokimura, H., Tokimura, Y., Oliviero, A., Asakura, T., Rothwell, J.C., 1996. Speech-induced
changes in corticospinal excitability. Ann. Neurol. 40, 628–634.
Tramo, M.J., 2001. Biology and music. Music of the hemispheres. Science 291, 54–56.
Uozumi, T., Tamagawa, A., Hashimotor, T., Tsuji, S., 2004. Motor hand representation in
cortical area 44. Neurology 62, 757–761.
van Vugt, F.T., Kafczyk, T., Kuhn, W., Rollnik, J.D., Tillmann, B., Altenm€
uller, E., 2014. The
role of auditory feedback in music-supported stroke rehabilitation: a single-blinded ran-
domised controlled intervention. Brain Inj. (Submitted).
Vaquero, L., Hartmann, K., Ripolle
´s, P., Rojo, N., Sierpowska, J., Ca
´mara, E.,
Mohammadi, B., Samii, A., M€
unte, T.F., Rodriguez-Fornells, A., Altenm€
uller, E.,
2014. The earlier, the smaller: neuroplastic changes in professional pianists depend on
age of onset. NeuroImage (Submitted).
Wade, D.T., Hewer, R.L., David, R.M., Enderby, P.M., 1976. Aphasia after stroke: natural
history and associated deficits. J. Neurol. Neurosurg. Psychiatry 49, 11–16.
251References
Author's personal copy
Wan, C.Y., Schlaug, G., 2010. Music making as a tool for promoting brain plasticity across the
life-span. Neuroscientist 16, 566–577.
Wan, C.Y., R€
uber, T., Hohmann, A., Schlaug, G., 2010. The therapeutic effects of singing in
neurological disorders. Music. Percept. 27, 287–295.
Wan, C., Zheng, X., Marchina, S., Norton, A., Schlaug, G., 2014. Intensive therapy induces
contralateral white matter changes in chronic stroke patients with Broca’s aphasia. Brain
Lang. 136, 1–7.
Wilson, S.J., Parsons, K., Reutens, D.C., 2006. Preserved singing in aphasia: a case study of
the efficacy of the melodic intonation therapy. Music. Percept. 24, 23–36.
Zatorre, R.J., Belin, P., 2001. Spectral and temporal processing in human auditory cortex.
Cereb. Cortex 11, 946–953.
252 CHAPTER 12 Apollo’s gift
Author's personal copy
