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doi:10.

1093/brain/awv286 BRAIN 2015: 138; 3793–3802 | 3793

Minds on replay: musical hallucinations and


their relationship to neurological disease
Erin C. Golden and Keith A. Josephs

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The phenomenon of musical hallucinations, in which individuals perceive music in the absence of an external auditory stimulus,
has been described sparingly in the literature through small case reports and series. Musical hallucinations have been linked to
multiple associated conditions, including psychiatric and neurologic disease, brain lesions, drug effect, and hearing impairment.
This study aimed to review the demographics of subjects with musical hallucinations and to determine the prevalence of neuro-
logical disorders, particularly neurodegenerative disease. Through the Mayo medical record, 393 subjects with musical hallucin-
ations were identified and divided into five categories based on comorbid conditions that have been associated with musical
hallucinations: neurological, psychiatric, structural, drug effect and not otherwise classifiable. Variables, including hearing impair-
ment and the presence of visual and other auditory hallucinations, were evaluated independently in all five groups. The mean age
at onset of the hallucinations was 56 years, ranging from 18 to 98 years, and 65.4% of the subjects were female. Neurological
disease and focal brain lesions were found in 25% and 9% of the total subjects, respectively. Sixty-five subjects were identified with
a neurodegenerative disorder, with the Lewy body disorders being the most common. Visual hallucinations were more common in
the group with neurological disease compared to the psychiatric, structural, and not otherwise classifiable groups (P 5 0.001),
whereas auditory hallucinations were more common in the psychiatric group compared to all other groups (P 5 0.001). Structural
lesions associated with musical hallucinations involved both hemispheres with a preference towards the left, and all but two
included the temporal lobe. Hearing impairment was common, particularly in the not otherwise classifiable category where
67.2% had documented hearing impairment, more than in any other group (P 5 0.001). Those with an underlying neurodegen-
erative disorder or isolated hearing impairment tended to hear more persistent music, which was often religious and patriotic
compared to those with a structural lesion, where more modern music was heard, and those with psychiatric disorders where music
was mood-congruent. This case series shows that musical hallucinations can occur in association with a wide variety of conditions,
of which neurological disease and brain lesions represent a substantial proportion, and that Lewy body disorders are the most
commonly associated neurodegenerative diseases. A future prospective study would be helpful to further delineate an association
between musical hallucinations and neurodegenerative disease.

Department of Neurology, Division of Behavioural Neurology, Mayo Clinic, Rochester, Minnesota, USA
Correspondence to: Keith A. Josephs, MD, MST, MSc
Professor of Neurology
Mayo Clinic
200 1st Street S.W.
Rochester, MN, 55905, USA
E-mail: Josephs.keith@mayo.edu

Keywords: music; psychosis; dementia; depression; Lewy body disease


Abbreviation: NOC = not otherwise classifiable

Received May 14, 2015. Revised July 27, 2015. Accepted August 9, 2015. Advance Access publication October 7, 2015
ß The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
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3794 | BRAIN 2015: 138; 3793–3802 E. C. Golden and K. A. Josephs

multifactorial pathophysiological process (Evers and


Introduction Ellger, 2004). Lesions anywhere along the auditory path-
‘Music, when soft voices die; Vibrates in the memory’ way, from the ear to the auditory association cortex, can
mused English poet Percy Bysshe Shelley (Shelley, 1901). lead to musical hallucinations (Cope and Baguley, 2009). In
The relationship between music and memory is particularly keeping with Berrios’ reported association between brain
highlighted by the curious phenomenon of musical hallu- disease and musical hallucinations, case reports detailed
cinations (Wieser, 2003; Sacks, 2006). musical hallucinations occurring in the setting of cerebral
An auditory hallucination, or the perception of sound in ischaemia (Calabro et al., 2012; Dinges et al., 2013; Woo
the absence of an acoustic stimulus, is not an uncommon et al., 2014), encephalitis (Douen and Bourque, 1997),
phenomenon. Auditory hallucinations usually consist of un- tumour (Scott, 1979; Nagaratnam et al., 1996), post-
formed sounds, such as those heard in tinnitus; however, surgery (Keshavan et al., 1988; Isolan et al., 2010), mul-
formed or complex hallucinations are experienced less tiple sclerosis (Husain et al., 2014) and epilepsy (Roberts
et al., 2001; Gentile et al., 2007; Ozsarac et al., 2012).

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frequently. Musical hallucinations represent a subset of
complex auditory hallucinations in which individuals per- Given the strong association between hearing impairment
ceive music in the form of tunes or melodies, which can be and musical hallucinations, some have suggested that mu-
continuous or intermittent, in the absence of a correspond- sical hallucinations represent a release phenomenon.
ing external stimulus. Sometimes, singing voices may According to one proposal, sensory deprivation eliminates
accompany the music (Berrios, 1990; Warner and Aziz, the afferent input to the auditory sensory processing system
2005). The hallucinations can be transient or long-lasting. allowing spontaneous activity to occur in a network
Often occurring in cognitively and psychiatrically normal (Griffiths, 2000), analogous to the Charles Bonnet syn-
individuals, they are likely under-reported due to concern drome, in which visual impairment precipitates the devel-
opment of visual hallucinations (Burke, 2002). A significant
for being perceived as ‘crazy’. In addition, it may be that
proportion of patients with the Charles Bonnet syndrome
the music is not bothersome or disruptive to daily function-
eventually develop dementia with Lewy bodies (Lapid
ing and so does not prompt a discussion with a medical
et al., 2013). However, the prevalence of neurodegenerative
provider. Often, the tunes are familiar to the person per-
disorders among those who experience musical hallucin-
ceiving them, but there are reports of novel or unfamiliar
ations, and how these subjects compare to those with mu-
tunes (Berrios, 1990; Warner and Aziz, 2005). Even when
sical hallucinations in the setting of other disorders has not
the melody is unrecognizable to the subject, it may repre-
been addressed in the literature to date. Musical hallucin-
sent a familiar melody that is no longer consciously remem-
ations are often noted to occur in cognitively normal
bered by the subject (Vitorovic and Biller, 2013), a
people; however, anecdotally musical hallucinations have
phenomenon that has prompted important questions as to
been described to occur in the presence of dementia
whether our memory for music is distinct from other
(Mori et al., 2006; Berger, 2015).
memories.
In this study, we sought to address this knowledge gap
Musical hallucinations are an uncommon phenomenon.
by characterizing the conditions associated with musical
In one series of general psychiatric admissions, the preva-
hallucinations through a large case series. We further
lence rate was 0.16% (Fukunishi et al., 1998). In another
aimed to further explore the prevalences and characteristics
series of elderly subjects at an audiology clinic, approxi-
of neurological diseases, particularly neurodegenerative, in
mately one-third experienced auditory hallucinations, but
those experiencing musical hallucinations compared to
of these only one subject (or a total of 0.8%) experienced
groups without an associated neurological disease. Given
musical hallucinations (Cole et al., 2002).
the previous literature, we hypothesized that structural
More detailed reports of musical hallucinations have
lesions would have a significant preference towards the
been published, albeit sparingly. Berrios (1990) published
right hemisphere. We further predicted an association
the first series of subjects with musical hallucinations and
between musical hallucinations and neurodegenerative dis-
identified that they were more often seen in females com-
orders, specifically Lewy body disorders, given their known
pared to males, and positively correlated with advancing
correlation with hallucinations.
age, deafness, and brain disease. Since the Berrios (1990)
study, literature reviews compiling case reports and small
case series have been published (Keshavan et al., 1992;
Evers and Ellger, 2004); however, no large single centre Materials and methods
case series has been published to date.
The most commonly accepted predisposing condition for Subjects
the development of musical hallucinations has been shown The research project was approved by the Mayo Institutional
to be hearing impairment, however, most people who have Review Board. The Mayo Clinic Medical Records Linkage
significant hearing impairment never develop musical hal- System was used to identify all subjects who underwent evalu-
lucinations. Therefore, hearing impairment represents one ation at this institution and had musical hallucinations from 1
variable in what likely represents a complex and January 1996 to 31 December 2013. The system was queried
Musical hallucinations and associated neurological conditions BRAIN 2015: 138; 3793–3802 | 3795

to capture all medical records in which the terms ‘musical If significance was found, the Tukey-Kramer post hoc test
hallucinations’, ‘music AND hallucinations’, and ‘hear music’ was then used to compare all pairs of groups.
including all tenses of ‘hear’ appeared. The medical records of We did not adjust for multiple comparisons in our study
all subjects identified were then reviewed to determine whether given that we had an a priori hypothesis for testing for these
they met criteria for musical hallucinations defined as the per- associations. In addition, adjusting for multiple comparisons
ception of music not perceived by others present. Subjects were would have increased the likelihood of type II errors for asso-
only included if they were at least 18 years old and the symp- ciations that were not null. Not adjusting for multiple com-
tom of musical hallucinations was documented in a clinical parisons has been advocated since it will result in fewer errors
encounter with a Mayo Clinic provider including physician, in interpretation when the data are not random numbers but
nurse practitioner, or psychologist. Subjects who only experi- actual observations in nature (Rothman, 1990). Therefore,
enced isolated hypnagogic or hypnopompic hallucinations adjusting our data could have resulted in missing important
were excluded. Clinical data were abstracted in all subjects findings.
that met the inclusion criteria, including age at onset of
musical hallucinations, the presence of visual or other auditory

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hallucinations, available imaging, documentation of hearing
impairment, and audiometry. Subjects were divided into five
Results
categories according to the condition felt to be most strongly A total of 636 subjects were identified by the Mayo
associated with musical hallucinations, recognizing that often Medical Records Linkage System. Of these, 393 met inclu-
multiple factors may have contributed. The five categories sion criteria. The mean age at onset of the hallucinations
included neurologic, psychiatric, structural, drug toxicity or
was 56 years (range 18–98). Two hundred and fifty-seven
withdrawal and not otherwise classifiable (NOC) for those
(65.4%) of these subjects were female. One hundred and
not fitting into the other four groups. Subjects with musical
hallucinations were grouped in the neurologic category if the
five (26.7%) subjects had documented hearing impairment,
hallucinations developed in the setting of a neurological dis- 77 of whom had audiometry confirming hearing impair-
order. Within the neurologic category, those with a neurode- ment. While most subjects underwent head CT imaging,
generative disease were further subclassified to assess for 207 (52.8%) had head MRI performed. Generalized atro-
associations. All subjects were subclassified based on the diag- phy, leukoaraiosis, and lacunar infarcts were common
nosis rendered by the evaluating neurologist. Subjects were findings.
subclassified as having a Lewy body disorder (Parkinson’s dis- After division into groups (Fig. 1), psychiatric disorders
ease, Parkinson’s disease dementia, dementia with Lewy predominated (39%) with neurological disorders (25%) the
bodies), Alzheimer’s dementia or frontotemporal dementia next most common. Drug toxicity or withdrawal, structural
based on accepted diagnostic criteria. Others were diagnosed lesions, and NOC made up a smaller proportion of the
with dementia without a more specific diagnosis (dementia not total subjects. Co-existing auditory and visual hallucin-
otherwise specified or dementia NOS.) Sometimes those with a
ations were relatively common, as detailed in Table 1.
neurologic diagnosis had concomitant psychiatric disease,
Examples of specific songs or music genres for each of
often as a neuropsychiatric symptom related to the neuro-
logical disease, and these subjects remained in the neurologic the five categories are shown in Table 2. Musical hallucin-
group given the main aim of our study. Subjects were placed in ations were sometimes transient particularly when asso-
the structural category if they clearly developed musical hallu- ciated with a reversible neurological condition, structural
cinations in the context of a focal brain lesion, with imaging lesion or drug effect. Often however, particularly in the
done in close temporal relationship to the hallucinatory experi- neurodegenerative and NOC groups, the hallucinations
ence. Subjects who experienced seizures related to focal lesions were persistent, lasting for months to years at a time.
were included in the structural category. Subjects placed in the Descriptions of these experiences are provided in
psychiatric category experienced musical hallucinations that Supplementary Box 1.
were clearly associated with worsening of psychiatric symp-
toms. For subjects in the drug category, there was a clear
temporal relationship between the initiation of a drug or the Neurologic group
withdrawal state and the musical hallucinations, which was
A total of 98 patients had a primary neurologic diagnosis
noted by either patient and/or care provider. Co-morbid psy-
associated with the hallucinations. The mean age in this
chiatric conditions were collected for subjects in all groups.
category was 64 years (range 18–98), which was signifi-
cantly different than the mean age of all other groups
Statistical analyses and second oldest to the mean age of the NOC group,
and 71.4% were female. Of these subjects, 32.7% had
Statistical analyses were performed using JMP statistical soft-
documented hearing loss, and 71.8% of subjects with hear-
ware (JMP, version 10.0.0; SAS Institute Inc, Cary, North
Carolina), with statistical significance set at P 5 0.05. Sex
ing loss had supporting audiometry. By far, the most
ratios and binary variables collected (presence or absence of common neurological diagnosis seen was a neurodegenera-
hearing impairment, visual or other auditory hallucinations) tive disorder (67.3%), followed by seizures (16.3%), and
were compared across groups and subgroups using the 2 encephalitis (9.2%) (Table 3). The most common of the
test. Age at musical hallucination onset was compared across neurodegenerative diseases was Lewy body disease
groups and subgroups using the analysis of variance test. (34.8%) (Table 3). Of the Lewy body disorders, dementia
3796 | BRAIN 2015: 138; 3793–3802 E. C. Golden and K. A. Josephs

mood, and at least two were associated with a deceased


person. Auditory hallucinations were significantly more
common in those in the psychiatric group than in all
other groups. The frequency of hearing impairment was
significantly less than for all other groups excluding struc-
tural, for which it was similar.

Structural group
Thirty-seven subjects (9%) had structural lesions associated
with the musical hallucinations. Of the 37, all had MRI
completed except for two who had a head CT and one
who did not have imaging available for review but had a

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history of a right temporal astrocytoma resection several
years earlier, after which he developed seizures manifesting
as musical hallucinations attributed to the lesion. The mean
age was 43.5 years (range 18–87), and 48.9% were female.
Hearing loss was documented in 13.5%, and 80% of these
subjects had supporting audiometry. As shown in Table 5,
Figure 1 The proportions of musical hallucinations the most common structural lesion noted was tumour
attributed to different associated conditions. Psychiatric dis- (n = 14 subjects), with a lesser frequency of post-surgical
ease represented the most commonly associated condition; how-
lesions (comprised of resections of tumours, vascular
ever, neurological disease and focal brain lesions together accounted
anomalies, and a non-structural epileptic focus), mesial
for over a third of the patients.
temporal sclerosis and undifferentiated lesions.
Interestingly, only two subjects experienced musical hallu-
with Lewy bodies was the most common (60.9%), followed cinations following an infarct documented by imaging.
by Parkinson’s disease and Parkinson’s disease dementia. Tumours tended to be low grade (meningioma, oligo-
Often, those with neurodegenerative disorders did not dendroglioma, low-grade glioma, pilocytic astrocytoma)
have the insight that their hallucinations represented false (n = 9 subjects) compared to high-grade glioma (n = 5 sub-
perceptions and were convinced that the neighbours were jects). Temporal lobe involvement was noted with all the
playing music too loudly. One subject was described to go structural lesions with the exception of two, a tumour
around ‘knocking on neighbours doors and at times har- located in the pons with extension into the midbrain and
assing them as a result of this symptom’. Songs were often cerebellum and a right parietal infarct. Both the right and
religious or patriotic, and reminiscent of childhood. Visual left hemispheres were involved. More lesions were noted in
hallucinations were significantly more common in those in the left hemisphere (57%) compared to the right hemi-
the neurologic group relative to those in the psychiatric, sphere, however to an insignificant degree. Examples of
structural, and NOC groups. Thirty-four per cent of lesions resulting in musical hallucinations are shown in
those in the neurologic group had a comorbid psychiatric Fig. 2. Songs heard were often more modern, including
diagnosis: depressive disorders (n = 23), anxiety disorders genres like country and rock. Twenty-seven per cent of
(n = 6), psychotic disorders (n = 2), and bipolar disorder those in the structural group had a co-morbid psychiatric
(n = 2). With the exception of bipolar disorder, many of diagnosis: depressive disorders (n = 6), anxiety disorders
these diagnoses were neuropsychiatric symptoms secondary (n = 2), psychotic disorders (n = 2).
to the neurological disease.
Drug toxicity or withdrawal group
Psychiatric group Forty-five subjects experienced the onset of musical hallu-
The mean age in the psychiatric category was 48.1 years cinations in close temporal relationship to drug initiation or
(range 8–90), and 70.3% were female. Of these, 11.6% in the setting of withdrawal. The mean age in this group
had documented hearing loss, and 72.2% of subjects with was 54 years (range 19–91), and 51.1% were female. Of
hearing loss had supporting audiometry. Depression and these subjects, 24.4% had documented hearing loss, 63.5%
bipolar disorder accounted for the majority of diagnoses of which had supporting audiometry. The most commonly
and there tended to be waxing and waning of the hallucin- associated subgroups were alcohol withdrawal and ster-
ations with depressive and manic symptoms (Table 4). oids. Table 6 is a complete list of drugs. Alcohol abuse
Psychotic disorders represented a smaller proportion was a common confounder in the psychiatric population,
(17.4%) with schizoaffective disorder being the most often accompanying depression. All cases of stimulants
predominant of those. Only one person had obsessive- were in association with polysubstance abuse. In 48.9%
compulsive disorder. Songs tended to be affected by of subjects, the hallucinations resolved completely upon
Musical hallucinations and associated neurological conditions BRAIN 2015: 138; 3793–3802 | 3797

Table 2 Description of music heard across groups

50.0001a,b,c,d,g,i,j

50.0001a,b,d,f,g,i,j

50.0001a,b,d,e,h
50.0173b,c,e,f

50.0001a,e,f,g
Category Description

P-values*

Neuro versus Psych; bNeuro versus Structural; cNeuro versus Drug; dNeuro versus NOC; ePsych versus Structural; fPsych versus Drug; gPsych versus NOC; hStructural versus Drug; iStructural versus NOC; jDrug versus NOC.
Neurologic
Neurodegenerative ‘church choral music’

39 (67.2%)
39 (67.2%)
17 (29.3%)
‘echo of last music he heard’

7 (12.1%)
73 (12.9)
‘big band’ (n = 2 subjects)
Structural NOC
‘single tune with the words “where were
58 you when the Lord was crucified” or

18 (48.9%)

10 (27.0%)
5 (13.5%)
44 (19.2)

1 (2.7%)
“where were you when your Lord was
placed in the grave, 24 hours a day”
37

‘church hymns’
23 (51.1%)
11 (24.4%)

12 (26.7%)
7 (15.6%)
Structural
54 (19.0)

‘rock music’

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Drugs

‘old video game’


45

‘Fraggle rock’
109 (70.3%)
18 (11.6%)
74 (47.8%)
33 (21.3%)

‘country music’ (n = 2 subjects)


48 (15.5)

‘Queen’
Dementia NOS All Neurodegenerative Psych
155

‘hearing a record playing over and over


again which appeared to skip at times’
Psychiatric ‘believes it was someone who had
passed away’
‘fun and snappy but scary’
‘radio playing in another room’
(70.8%)
(41.5%)
(29.2%)
(49.2%)
(11.1)

‘favorite songs of late husband’


Psych = psychiatric; LBD = Lewy body disease; AD = Alzheimer’s disease; FTD = frontotemporal dementia; NOS = not otherwise specified.

‘like funeral music when depressed’


65
74
46
27
19
32

‘music from Beauty and the Beast’


‘hard rock’
Drug ‘elevator music’
19 (86.4%)
8 (36.4%)
7 (31.8%)
7 (31.8%)
73 (12.7)

‘Yankee Doodle Dandy’


‘Bram’s type music’
22

‘Christmas carols’ (n = 2 subjects)


2 (100%)

‘string instruments’
1 (50%)
1 (50%)
0 (0%)
59 (3)
FTD

‘radio through vent’


Not otherwise
2

‘school songs and hymns’


Table 1 Demographic features across all five categories groups

14 (77.8%)
Neurodegenerative

*All of the results except for the gender association would have survived Bonferroni correction.

classifiable
8 (44.4%)
7 (38.9%)
7 (38.9%)

‘Glory, Glory, Alleluia’


78 (8.5)

‘Silent Night, O Holy Night, Edelweiss,


AD
18

The Battle Hymn of the Republic’


12 (52.2%)
11 (47.8%)

17 (73.9%)
4 (17.4%)

‘America the Beautiful sung as by a choir


72 (9.9)

with an orchestra which lasted four to


All neurologic LBD
23

five months. . .[which] changed to a


hymn, then a Christmas song, then to
Neurological

presently single notes.’


(71.4%)
(32.7%)
(25.5%)
(38.8%)
(19.6)

‘How much is that doggy in the window,


The Star Spangled Banner and Swing
98
64
70
32
25
38

Post hoc P-values were considered significant if 50.05.

Low-Sweet Chariot’
other auditory hallucinations

‘Japanese’
‘Polish’
visual hallucinations
hearing impairment

‘Marine call, Silent Night, Little Drummer


Boy, isolated trumpet or bugle calls or
female gender

clarinet or flute music’


‘almost constantly, I Walk the Line and
(SD)

This Land Is Your Land’


‘National anthem’
Age at onset
Frequency of
Frequency of
Frequency of
Frequency of

‘Star-Spangled banner’
n

a
3798 | BRAIN 2015: 138; 3793–3802 E. C. Golden and K. A. Josephs

Table 3 All neurological diagnoses associated with Table 4 All psychiatric disorders associated with mu-
musical hallucinations sical hallucinations

Neurological diagnosis n Psychiatric diagnosis n


Neurodegenerative 65 Depression 62
Lewy body disorders 23 Bipolar disorder 29
Dementia with Lewy bodies 14 Schizoaffective disorder 12
Parkinson’s disease 5 Anxiety 13
Parkinson’s disease dementia 4 Delirium 10
Dementia NOS 22 Psychotic disorder NOS 9
Alzheimer’s dementia 18 Schizophrenia 6
Frontotemporal dementia 2 Spell 6
Seizure 16 Post-traumatic stress disorder 3
Encephalitis 9 Obsessive compulsive disorder 1

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Post-concussive syndrome 2 Chronic fatigue syndrome 1
Amyloid beta related angiitis 1 Dysthymia 1
Migraine 1 Adjustment disorder 1
Posterior reversible encephalopathy syndrome 1 Mood disorder NOS 1
Traumatic brain injury 1
Leukoencephalopathy 1
Multiple system atrophy 1
divided). It remains unclear why there would be a female
predominance amongst those with musical hallucinations in
these groups, and likely the cause is multifactorial and com-
cessation of the offending drug or withdrawal syndrome. In plex, possibly related to underlying structural or metabolic
two subjects (4.4%), the hallucinations improved, and in differences between genders. Data evaluating gender differ-
another two subjects, no improvement was noted. In the ences in hallucinations associated with psychiatric and
remainder of subjects, follow-up information was not avail- neurological disease is sparse; however, there is some lit-
able. A high proportion (64%) of subjects in this group had erature to suggest that hallucinations are more common in
a comorbid psychiatric diagnosis: depressive disorders females in psychiatric disease (Rector et al., 1992) and
(n = 17), anxiety disorders (n = 8), bipolar disorder dementia (Xing et al., 2012).
(n = 3), and psychotic disorders (n = 1). The average ages at which the individuals in the neuro-
logic and NOC groups experienced musical hallucinations
were significantly higher than other groups, and that of the
Not otherwise classifiable group neurodegenerative disorders group was quite similar to that
For those not otherwise classifiable (NOC), the average age of the NOC group, namely 74 and 73 years, respectively.
was 73 years (range 36–94), which was significantly greater Neurological disease and structural lesions were associated
than the mean age of all other groups, and 67.2% were with musical hallucinations in a significant proportion of
female. Of these subjects, 67.2% had hearing impairment, subjects—a total of 135. Several of the subjects included in
74.4% of which had supporting audiometry. There were the psychiatric group presented with new-onset psychosis at
no unifying underlying co-morbidities; however, interest- an older age but did not have a neurological evaluation or
ingly two subjects developed musical hallucinations after cognitive screening. For some of these subjects, follow-up
cochlear implants. As in the neurologic category, many of in the institution was lacking, raising the question as to
these subjects heard songs familiar to them from childhood, whether some may have had underlying neurodegenerative
particularly religious or patriotic songs. Twenty-six per cent disease.
of subjects in this group had a co-morbid psychiatric diag- Hearing impairment was common across groups, particu-
nosis: depressive disorders (n = 9), anxiety disorders (n = 5), larly in the relatively small proportion of NOC subjects.
and psychotic disorders (n = 1). The prevalence of documented hearing impairment was sig-
nificantly higher in the NOC group than the other groups
and audiometry was not available for those who denied
Discussion hearing impairment or for whom it was unknown in this
group, which may suggest the prevalence was even higher.
This study represents the largest series of musical hallucin- As the history and exam had not identified co-morbidities
ations to date, from which several important points can be or toxicity in the NOC group, which might otherwise have
highlighted. Similar to previous studies (Berrios, 1990; been associated with the hallucinations, the high incidence
Keshavan et al., 1992; Evers and Ellger, 2004) most of of hearing impairment instead supports the established
the individuals experiencing musical hallucinations were theory that isolated peripheral auditory dysfunction alone
female (with the exception of those related to structural can lead to musical hallucinations (Gordon, 1997).
lesions and drugs where the genders were fairly equally However, deafness with normal central functioning does
Musical hallucinations and associated neurological conditions BRAIN 2015: 138; 3793–3802 | 3799

Table 5 All structural lesions associated with musical musical imagery and perception, the primary auditory
hallucinations cortex is not necessarily activated in musical imagery
(Cope and Baguley, 2009). In a model proposed by
Structural Location n
Griffiths (2000), hearing impairment decreases auditory
Tumour Left temporal Total = 14 input to the primary auditory cortex, releasing basal inhib-
Left frontotemporal 8
ition on the auditory association cortex allowing for spon-
Left temporoparietal 3
taneous activity and potentially augmenting connections
Right parietotemporal 1
Right pons, midbrain, 1
with areas that encode and recognize patterned sounds
cerebellum 1 such as music. It is suggested that the threshold for spon-
Post-surgical lesion Total = 7 taneous activity varies between people and may be lowered
Right temporal 4 by disease or toxicity affecting the auditory pathway
Right frontotemporal 1 (Griffiths, 2000; Kumar et al., 2014). This study character-
left temporoparietal 1 izes a variety of conditions associated with musical hallu-

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Left temporal 1 cinations that may act to lower the threshold for
Mesial temporal sclerosis Total = 4
spontaneous activity of the auditory pathway.
Right 2
Left 2
Notably, the structural lesions we found associated with
Undifferentiated lesion Total = 3 musical hallucinations involved both hemispheres with an
Left frontotemporal 1 insignificant preference to the left as opposed to previous
Right temporal 1 studies, which have shown a marginal preference toward
Left temporal 1 the right (Berrios, 1990; Keshavan et al., 1992). All lesions
Infarct Total = 2 involved the temporal lobe with the exception of one sub-
Left temporal 1
ject who had a brainstem tumour with a separate lesion in
Right parietal 1
the cerebellum and another in whom musical hallucinations
Encephalomalacia Total = 4
Bilateral parietal, right 1 developed after a right parietal stroke. This case series pro-
temporal, occipital, and vides novel support for bilateral brain representation in the
cerebellum localization of musical hallucinations. Our series was able
Right frontotemporal 1 to capture all those who had addressed musical hallucin-
Left frontotemporal 1
ations with a care provider, even if not their major com-
Left temporal 1
plaint, and thus provided greater sensitivity for assessing
Arteriovenous malformation Right temporal 1
Arachnoid cyst Right temporal 1
the hemispheric predominance in focal brain lesions asso-
Subdural fluid Right hemisphere 1 ciated with musical hallucinations. One subject had a his-
tory of central pontine myelinolysis and developed alcohol
withdrawal-induced musical hallucinations, and perhaps
pre-existing pontine pathology predisposed him to this par-
not account for the fact that most people with hearing ticular drug effect. These findings match previous studies,
impairment never develop musical hallucinations and thus which have found lesions located along the auditory path-
an element of abnormal central processing must be impli- way and particularly the pons and temporal lobes resulting
cated even in this group (Stewart et al., 2006). Hearing in musical hallucinations (Douen and Bourque, 1997;
impairment was also relatively common in the neurologic Roberts et al., 2001; Isolan et al., 2010; Calabro et al.,
and drug group (32.7 and 24.4%, respectively), which 2012; Ozsarac et al., 2012; Serby et al., 2013; Woo
likely signifies that peripheral pathology can predispose a et al., 2014).
brain already made vulnerable from central dysfunction to It may be that deposition from neurodegenerative path-
musical hallucinations. Additionally, in the series, 11 of our ology can also act to disturb connections within the audi-
subjects with musical hallucinations had normal audiom- tory pathway and lower the threshold for spontaneous
etry, but had other associated psychiatric or neurological activity of the auditory association cortex. In one case of
diagnoses, directly contesting the idea that hearing impair- musical hallucinations in a subject with Alzheimer’s disease,
ment is a requisite to the development of musical hallucin- regional cerebral blood flow was increased in the left tem-
ations (Gordon, 1997). poral region and left angular gyrus (Mori et al., 2006). In
The exact mechanism behind which hearing impairment this series, Lewy body disorders accounted for the majority
can predispose an individual to musical hallucinations is of neurodegenerative disorders, and dementia with Lewy
unclear but has been hypothesized to be related to disin- bodies predominated amongst these. The prevalence of
hibition of the areas involved in musical imagery through visual hallucinations in this series in Alzheimer’s dementia
the reduction of external auditory input. Neural activation (38.9%) is higher than that reported by McKeith et al.
during musical imagery is remarkably similar to that in the (1992) and possibly some subjects with Alzheimer’s demen-
actual perception of music (Zatorre et al., 1996; Halpern tia had co-existing dementia with Lewy bodies.
and Zatorre, 1999; Kumar et al., 2014). However, while Additionally, in the subjects who had an undifferentiated
activity in the auditory association cortex is seen in both dementia, the high prevalence of visual hallucinations
3800 | BRAIN 2015: 138; 3793–3802 E. C. Golden and K. A. Josephs

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Figure 2 Imaging in subjects with musical hallucinations related to structural lesions. (A) Coronal T2 FLAIR head MRI scan of a 33-
year-old female with focal epilepsy involving a musical aura with a right superior temporal pilocytic astrocytoma. (B) Coronal T1 gadolinium-
enhanced head MRI scan of an 87-year-old female with left temporal lobe radiation necrosis. (C) Axial T2 head MRI scan of a 69-year-old male with
high grade astrocytoma in the pons with extension into the midbrain. (D) Axial T1 gadolinium-enhanced head MRI scan of a 77-year-old female
with a right temporal arteriovenous malformation. (E) Axial T2 FLAIR head MRI scan of a 74-year-old male with a recent left insular infarction. (F)
Coronal T2 FLAIR head MRI of a 47-year-old female after resection of right mesiotemporal meningioma.

correlation of auditory hallucinations in Lewy body disease


Table 6 All drugs associated with musical hallucin- has not been demonstrated. The neurochemistry of psych-
ations, either in toxicity or withdrawal osis in dementia likely involves dysregulation of multiple
neurotransmitters (Lanari et al., 2006; Zahodne and
Drug n Fernandez, 2008); however, a cholinergic deficit in the tem-
Alcohol withdrawal 10 poral neocortex has been shown to be associated with hal-
Steroids 9 lucinations in both Lewy body and Alzheimer’s disease
Stimulants 5 (Perry et al., 1999; Ballard et al., 2005; Zahodne and
Opiates 4 Fernandez, 2008; Pinto et al., 2011). Indeed, preferential
Antidepressants 4 damage to the nucleus basalis of Meynert, from which a
Alcohol 2
significant proportion of the cholinergic neurons originate,
Opiate withdrawal 2
is greater in the Lewy body disorders compared to
Benzodiazepine withdrawal 2
Lisinopril 2
Alzheimer’s disease where dysfunction appears to be related
Pramipexole 1 to cholinergic axonal input to the neocortex, and the
Ramelteon 1 cumulative cholinergic deficit is greater in Lewy body dis-
Carbidopa/levodopa 1 ease (Perry et al., 1993). Further supporting a role for
Clarithromycin 1 acetylcholine in the development of psychosis, acetylcholin-
Polysubstance abuse 1 esterase inhibitors are effective in both Lewy body and
Alzheimer’s psychosis (Cummings, 2005; Zahodne, 2008).
Musical hallucinations have been effectively treated using
(31.8%) suggests that many may have underlying Lewy donepezil in at least one subject in the literature (Ukai
body disease. Lewy body deposition in the temporal lobe, et al., 2007) suggesting a contribution of the cholinergic
particularly in the amygdala and parahippocampus, deficit to the development of musical hallucinations similar
strongly correlates with the development of visual hallucin- to other hallucinations. We would propose that our finding
ations (Harding et al., 2002); however, the pathological that Lewy body disorders may be more associated with
Musical hallucinations and associated neurological conditions BRAIN 2015: 138; 3793–3802 | 3801

musical hallucinations than other neurodegenerative dis- provider, sometimes unsolicited and sometimes as part of
orders is due to a greater cholinergic deficit and possibly screening in neurologic or psychiatric review of symptoms,
due to early brainstem involvement, affecting the proximal which may have slightly shifted the population. Certainly,
auditory pathways. there were patients seen at Mayo Clinic during the study
Subjects who had musical hallucinations in association time period outside of neurology and psychiatry practices
with a neurodegenerative disease or with isolated hearing who were not screened for hallucinations. Detail concern-
impairment tended to hear music, which was more persistent ing hallucination characteristics and temporal profile was
over a longer time period. Several of these individuals experi- often lacking. Hearing impairment was not always screened
enced an interesting phenomenon where the music disinte- for or documented so its prevalence in this population was
grated over time into increasingly shorter melodies and tunes certainly falsely low.
and sometimes terminating in repetitive single notes well This study reviewed cases seen at Mayo Clinic across
described by one subject who reported that she ‘noted a specialties, including primary care, neurology, psychiatry,
change in the phenomena. . .such as hearing a certain otorhinolaryngology, and audiology, a design which

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phrase or line of a song being repeated “back and forth” offered a favourably large case series from which we
rather than hearing a full song in its entirety’. This was were able to analyse the demographics of musical hallucin-
described in the original series by Berrios (1990) and has ations and their association to comorbid conditions. In the
later been referred to by Sacks (2007). Sacks made the com- future, a cross-sectional population-based study would be
parison to telescoping, an analogous phenomenon in phan- informative to eliminate the bias associated with a single
tom limb sensation (another proposed release phenomenon) centre series. Additionally, a prospective study following
where sensation of the distal part of the phantom retracts those who have musical hallucinations compared to
over time (Nikolajsen and Jensen, 2001). age-matched controls with a standardized assessment of
Interestingly, qualitative differences emerged between hearing and neurological exam including formal cognitive
songs heard by subject groups. For those in the neurode- testing, would be helpful to better understand the rela-
generative and NOC groups, which also had the highest tionship between musical hallucinations and neurological
rates of hearing impairment, songs tended to date back to disease.
childhood and also represented likely overlearned material
given that they were commonly religious, patriotic, or cul-
tural songs. Those who experienced musical hallucinations
secondary to structural lesions, often in the context of a
Conclusion
musical aura, heard more modern music, such as country Musical hallucinations can occur in a wide variety of disease
or rock, likely not learned in childhood, whereas in psychi- states, of which neurological disorders and brain lesions repre-
atric causes, songs tended to be mood-congruent, either sad sent a substantial proportion. Neurodegenerative diseases rep-
or ‘scary’ music, and sometimes represented a reminder of resent a large subset of neurological disease which can be
a close acquaintance or family member who had died associated with musical hallucinations and of these, the Lewy
(Table 2). This difference may in part be related to musical body disorders tend to be seen commonly. Hearing impairment
preferences with age, with older individuals favouring reli- likely represents a variable predisposing to the phenomenon,
gious or traditional songs. However, the traditional songs and those groups with the highest rates of hearing loss hear
heard by the neurodegenerative and NOC groups are dis- songs (neurodegenerative and NOC) that tend to be derived
tinguished by their relatively high frequency throughout a from childhood compared to other groups. A future prospect-
lifetime and relationship to emotionally-charged situations. ive study would be helpful to further delineate an association
Thus, they may be more vulnerable to manifesting as between musical hallucinations and neurological disease.
hallucinations in the presence of hearing impairment or
neurodegenerative disease.
There were a number of limitations associated with this Funding
retrospective study. As previously noted by Keshavan and
colleagues (1992), dividing subjects creates boundaries for The study was funded by the Mayo Clinic Department of
a phenomenon that is likely multifactorial. However, we Neurology.
believe that the groupings are generally instructive when
viewed with an understanding that multiple variables
likely play a role in the development of musical hallucin- Supplementary material
ations. Subjects were divided into categories according to
Supplementary material is available at Brain online.
conditions associated with musical hallucinations; however,
psychiatric disorders were a common comorbidity in all
categories as detailed. There was an ascertainment bias pre-
sent in the study given that data collected were based on References
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