Keywords
Neurosciences - Music - Epilepsy - Hallucinations - Alzheimer Disease
INTRODUCTION
Music is an art form and a cultural expression that is rooted in human emotions, thoughts,
and traditions. Music transcends language and can evoke a wide range of feelings,
from joy and excitement to nostalgia and serenity. While its interpretation varies
across cultures and individuals, music is universally recognized as a fundamental
part of human experience, helping to connect people and supporting the creation of
identity and sense of belonging.[1]
[2]
Humans have an almost universal ability to recognize music, even when exposed to unfamiliar
styles, rhythms, or instruments. This innate capacity reflects the brain's specialized
networks for processing musical elements, creating a sense of structure that most
individuals can understand instinctively. This process is called music perception,
which is a complex ability that involves multiple brain areas that work together to
recognize and analyze music and evoke emotional and associative responses.[3]
Like most brain functions, music perception is influenced by a variety of factors,
including genetics and training. Genetic influences may affect the ability to recognize
pitch, rhythm, and harmony, leading to variations in musical talent and sensitivity
across individuals.[4] Environmental factors, such as early exposure to music and cultural context, also
play a significant role in shaping musical abilities, including music perception.[5] Music perception can be impacted by certain rare disorders.
The purpose of this review is to explore the physiological and pathological aspects
of music perception, a brain function that is rarely addressed in conventional neurology
training.
METHODS
The present critical review was conducted through a comprehensive literature search
in the PubMed/MEDLINE and LILACS electronic medical databases, focusing on peer-reviewed
articles published from 2000 to the present. The search strategy employed combinations
of the following key terms: music perception, music emotion, amusia, congenital amusia, absolute pitch, musicogenic epilepsy, musical seizures, musical hallucinations, music memory, and music and Alzheimer Disease.
During the selection process, the reference lists of initially identified articles
were also examined, leading to the inclusion of additional relevant studies not retrieved
in the primary search. The review encompassed articles of different methodological
designs, including systematic and narrative reviews, clinical studies involving patients
with neurological or psychiatric conditions, and experimental studies with healthy
volunteers, particularly those employing neuroimaging, electrophysiological methods,
or behavioral paradigms to investigate musical processing.
The selected literature was critically analyzed to identify the main findings, controversies,
and gaps in knowledge regarding the neural and cognitive mechanisms of music perception,
as well as the clinical and topographical correlates of its dysfunctions.
PHYSIOLOGICAL MECHANISMS OF MUSIC PERCEPTION
PHYSIOLOGICAL MECHANISMS OF MUSIC PERCEPTION
The brain regions involved in sound processing and music perception are illustrated
in [Figure 1]. The areas associated with musical perception will be presented, detailing how they
enable the brain to perceive music as a distinctive and unique phenomenon.
Figure 1 Different brain areas involved in music perception. In yellow, we highlighted the
areas associated with melody processing: the auditory cortex, left cuneus, and precuneus.
Pitch processing, also in yellow, is primarily localized within the Heschl's gyrus
and adjacent areas. In blue, we highlighted the areas associated with harmony processing,
the right inferior frontal gyrus, which interacts with the parietal and temporal areas.
In red, we highlighted the areas associated with rhythm processing, which involves
a bilateral cortico-subcortical network, including the superior temporal cortices,
supplementary motor area, putamen, and cerebellum. The left inferior frontal gyrus
and insula are implicated in the processing of sequential sounds, which are essential
for rhythm.[7]
[13]
[24]
Auditory cortices and hemispheric specialization
The auditory information travels from the auditory nerves to the cerebral cortex,
reaching the primary auditory cortex. This area is responsible for the initial processing
of auditory information. Sound wave frequencies are preserved through a process called
tonotopy, traveling from the ear to the brain in an organized manner that maintains
their specific pitches. The primary auditory cortex preserves a tonotopic organization
with higher pitched sounds being processed in its posterior region and low-pitched
sounds being processed in a more anterior region. This forms a map of tones allowing
the brain to accurately differentiate specific frequencies.[6]
The hemispheric specialization of the auditory cortex involves a division of tasks.
The left hemisphere is more involved in the analysis of temporal and sequential aspects
of sound, such as rhythm perception and linguistic processing. The right hemisphere
specializes in the perception of pitch and melodic aspects, such as intonation, harmony,
and timbre. This division explains why right hemisphere lesions can impair the ability
to recognize melodies or detect dissonance, while the basic rhythm perception is intact.
It is important to note that this hemispheric specialization is not entirely rigid.[7]
The secondary auditory cortex areas are involved in the advanced processing of auditory
stimuli:
-
Brodmann area 42 provides an initial interpretation of musical and speech characteristics;
-
The right hemisphere Brodmann area 22 contributes to music processing, particularly
in the perception of tonality, harmony, and consonance, which is crucial for distinguishing
pleasant (consonant) sounds from unpleasant (dissonant) ones 2;
-
The planum temporale (PT) plays a crucial role in speech perception in the left hemisphere,
while the right PT is important for melody perception and differentiating the emotional
quality of vocal sounds;[8]
-
The superior temporal gyrus (STS), especially in the right hemisphere, is associated
with non-verbal stimuli, including music and emotional voice aspects like tone and
intonatio.[9]
The different areas of the secondary auditory cortex work in conjunction. The left
hemisphere is more involved in processing linguistic and temporal structures, while
the right hemisphere is the most important for melody and harmony perception.
Perception of musical elements
Music perception is a holistic process in which the brain interprets all musical elements—such
as melody, rhythm, harmony, and timbre—as a cohesive experience. However, researchers
often study them separately for methodological purposes.
Melody
Melody perception is a complex process involving multiple areas of the brain, particularly
in the right hemisphere. The primary auditory cortex performs a basic analysis of
tones, while the secondary auditory cortex (including the STS and adjacent areas in
the right hemisphere) integrates tones into melodic patterns. The right hemisphere
is particularly important for perceiving melodic and harmonic aspects of music. The
PT and STS are involved in distinguishing musical from non-musical sounds and recognizing
melodic patterns. After initial melody perception, emotional regions of the brain,
such as the amygdala and orbitofrontal cortex, are activated, integrating melody recognition
with emotion.[10]
The understanding of the consonance (harmonious and pleasant sounds) and dissonance
(tense and “unresolved” sounds) perception has received contribution from functional
neuroimaging studies. Consonant sounds tend to generate higher activity in the secondary
auditory cortex and in limbic regions associated with emotion (such as the orbitofrontal
cortex), while dissonant sounds more intensely activate regions associated with threatening
or uncomfortable stimuli, such as the amygdala. The right hemisphere is the one more
involved in distinguishing consonance from dissonance.[11]
[12]
Rhythm
Rhythm perception depends not only on auditory areas but also on motor areas that
anticipate and synchronize rhythmic pulses. Hemispheric specialization also plays
an essential role. The left hemisphere is more active in analyzing complex and sequential
rhythms while the right hemisphere contributes more to the analysis of slower and
irregular rhythmic patterns.[13]
-
The premotor cortex and the supplementary motor area (SMA) are crucial for rhythm
perception and production. Studies show that they not only coordinate motor actions
during beat production but are also activated when a person merely listens to a rhythmic
sequence, indicating a connection between rhythm listening and motor preparation;[14]
[15]
-
The basal ganglia, including the caudate nucleus and putamen, are also fundamental
for rhythm perception and production. They play a role in detecting and maintaining
a regular pulse, particularly in continuous rhythms or when individuals need to keep
an internal tempo without an external cue;[16]
-
The cerebellum is important for fine motor control and coordination, as well as temporal
perception and precise regulation of rhythmic intervals. It helps adjust small variations
in beat duration and supports the perception of complex rhythmic patterns;[17]
-
The prefrontal and superior parietal cortices play roles in attentional control and
auditory working memory, essential for keeping rhythm in mind or following a beat
while attending to other information.[17]
Harmony
While melody tends to be linear and follows a single line of notes one after another,
harmony is multi-layered, providing a background that complements the melody's progression.
There are some differences and specificities in the perception of harmony and melody.
Harmony perception requires that the brain integrate multiple frequencies at once.
This involves greater participation from the right hemisphere, which is more specialized
in the spatial and simultaneous integration of sounds.[12]
Functional neuroimaging studies show that consonant chords activate the reward system,
providing a sense of pleasure, while dissonant sounds activate regions associated
with discomfort and alertness. Consonant chords more often activate the reward system,
including limbic areas like the nucleus accumbens and the amygdala. Melody also activates
emotional areas, but to a lesser extent. Emotional responses to melody tend to relate
more to familiarity and melodic progression than to consonance or dissonance.[18]
[19]
Harmony perception also involves the inferior frontal gyrus and inferior parietal
regions, which are crucial for aesthetic evaluation and the simultaneous integration
of multiple sound elements. Melodic processing generally relies less on aesthetic
integration networks in the frontal and parietal areas, and it is more related with
the auditory and motor areas, which follow and anticipate rhythm.[20]
Integrated processing
The perception of melody, harmony, timbre, and rhythm occurs simultaneously, creating
a cohesive experience, and it is believed that the processing of music involves unconscious
mechanisms that group and organize sounds into patterns, working as a probabilistic
system, in which the brain makes predictions about what will happen next based on
learned patterns.
The brain automatically groups the musical sounds in multiple dimensions:
-
a) Temporal grouping: an automatic division of music into rhythmic segments, occurring
in the auditory cortex and motor areas, such as the premotor cortex, which are activated
even without physical movement, suggesting an unconscious rhythmic anticipation.[21]
-
b) Melodic grouping: the brain identifies melodic patterns based on intervals and
pitch direction (such as ascending or descending note sequences). This melodic contour
recognition occurs automatically in the superior temporal gyrus.[22]
-
c) Harmonic grouping: This unconscious processing is mediated by the secondary auditory
cortex and parietal lobe areas, where harmonic combinations are interpreted automatically.[23]
These grouping processes generate coherent patterns. This process involves both bottom-up
and top-down processing, where sensory input of the sound is integrated and interpreted
based on prior knowledge and expectations. Probabilistic mechanisms play a crucial
role in this process by predicting the likelihood of certain musical events, such
as pitch sequences, rhythmic changes, or harmonic progressions. These predictions
are based on statistical regularities learned from exposure to music, allowing the
brain to anticipate upcoming events and respond more efficiently. This predictive
coding framework suggests that the brain continuously updates its expectations about
musical structure, adjusting its predictions when unexpected changes occur, creating
a dynamic interplay between expectation and perception in musical experience.[24]
[25]
Emotional processing of music
The main regions related to emotional response to music are:[26]
-
Amygdala: It is particularly responsive to intense or unexpected sounds, reacting
to changes in harmony or dissonance, triggering emotional responses such as joy, excitement,
or sadness, according to the music heard and the listener's expectations;
-
Hippocampus: It enhances the emotional impact of music when it evokes specific memories.
A familiar melody or music tied to a significant moment activates the hippocampus,
reinforcing the emotional response;
-
Reward system and musical pleasure: The nucleus accumbens and other areas within the
reward system (such as the orbitofrontal cortex) are activated in response to enjoyable
music. When exposed to music that evokes a sense of pleasure, this system increases
dopamine production.
Functional neuroimaging studies have shown different patterns of activation by listening
to music in major or minor keys. Music in major keys activates areas responsible for
pleasure and reward, such as the nucleus accumbens and orbitofrontal cortex, enhancing
feelings of wellbeing. When exposed to music in minor tones, the brain tends to exhibit
preferential activation of the amygdala and medial prefrontal cortex, evoking sadness,
melancholy, introspection, and sometimes nostalgia. Minor tones are frequently linked
to reflective or somber emotional states, as they tend to elicit a sense of emotional
depth and complexity.[18]
[27]
ABNORMALITIES OF MUSIC PERCEPTION
ABNORMALITIES OF MUSIC PERCEPTION
Musical perception abnormalities encompass a range of conditions that affect the ability
to process, interpret, or respond to musical stimuli. These abnormalities can result
from structural or functional impairments in the brain regions involved in musical
processing. [Table 1] summarizes the main disorders of musical perception, their topographic correlations,
and causes.
Table 1
Types of musical perception disorders and their clinical features, topographic correlations,
and causes
|
Disorder
|
Features
|
Topographic correlation
|
Cause
|
|
Congenital amusia
|
Inability to recognize and remember musical melodies are the key phenotypic features
|
Involvement of connecting fibers in the fasciculi and corpus callosum.
|
It is an unknown cause, although a genetic influence has been demonstrated in epidemiological
studies.
|
|
Musical aphasia
|
Acquired language and music perception involvement
|
Left temporal lesion
|
Stroke, brain tumor, frontotemporal dementia
|
|
Acquired amusia
|
Acquired and isolated music perception involvement
|
Right temporal superior gyrus
|
Stroke, brain tumor, frontotemporal dementia
|
|
Musicogenic epilepsy
|
Epileptic seizures triggered by music.
|
Medial and lateral temporal lobes and insula
|
Mesial temporal sclerosis and other structural brain abnormalities, anti-glutamic
acid decarboxylase 65 encephalitis
|
|
Musical hallucination
|
Auditory hallucination related to music
|
Central or peripheric lesions involving structures of the auditory system
|
Hearing loss, focal brain lesions, psychiatric disorders, medications
|
|
Absolute pitch
|
Enhanced ability to identify and name pitches without any reference
|
Higher connectivity between auditory and memory areas of both hemispheres
|
Genetic and early musical training
|
Amusia
The most representative alteration in this spectrum is amusia, a condition characterized
by difficulties in pitch recognition (tonal amusia), rhythm perception (rhythmic amusia),
or melodic memory (melodic amusia). The term was August Knoblauch in 1888.[28] This condition can be either congenital, present from birth, or acquired, typically
developing because of a brain injury. The different types of amusia are described
below:
Congenital amusia
Congenital amusia is caused by structural and functional changes in the auditory cortex,
particularly in the superior temporal gyrus. People with congenital amusia typically
cannot detect pitch variations and may be insensitive to basic musical structure.
It was first characterized by Peretz in 2002 as a condition in which music perception
is abnormal despite normal hearing and preserved cognition.[29]
A persistent inability to recognize and remember musical melodies are the key phenotypic
features. This deficit extends to musical memory and includes difficulties in perceiving
pitch and rhythm. The condition is usually noticed during school years when children
show an inability to perform musical tasks, such as singing or playing instruments,
even percussion ones. Amusia manifests from birth, and daily exposure to music does
not improve the condition.[30]
[31]
[32]
There is no associated hearing loss, brain damage, or intellectual impairment. There
are only inconsistent associations with dyslexia and difficulties in spatial orientation.
Language acquisition in individuals with amusia is slightly slower in the early stages
but later normalizes. Intellectual development in people with amusia is fully within
the expected range.[30]
[31]
[32]
[33] Some famous people considered to have high intellectual capacity, including two
presidents of United States, Ulysses S. Grant and Theodore Roosevelt, reportedly had
amusia.[34]
The diagnosis of congenital amusia can be supported by the Montreal Battery of Evaluation
of Amusia (MBEA), which is a battery of tests that assesses musical abilities related
to six components of musical processing: contour (pitch direction - ascendant and
descendant); scale (tonal encoding of a melody); interval (perception of distances
between two successive pitches); rhythm (perception of the temporal dimension of a
melody); meter (perception of the pulse of a melody); and musical memory (recognition
of musical phrases after implicit storage). An adapted version of the MBEA has been
used in Brazil.[27]
Neurobiological basis
Reduced connectivity between the left and right auditory cortices has been observed
in individuals with amusia, meaning that musical signals are correctly recruited but
processed in a separate way in both hemispheres, creating a dual signal stream which
is not jointly analyzed in the brain.
Neuroimaging studies show that people with amusia have higher diffusivity indices
in the corpus callosum and in the right occipital fasciculus. In amusic individuals,
the axial diffusivity in these structures negatively correlates with musical performance
scores. These findings support the recognition of congenital amusia as a disconnection
syndrome, as the corpus callosum and occipital fasciculus are structures involved
in connecting different cortical areas.[35] Morphological studies have revealed abnormalities in the volume of white and gray
matter in the right inferior frontal gyrus and the right superior temporal gyrus in
the brains of people with amusia.[36]
Magnetoencephalography studies have demonstrated reduced intrinsic connectivity in
the auditory cortex of both hemispheres and reduced right frontotemporal feedback
connectivity in individuals with amusia compared with controls.[32] One study tested the response to harmonic structures in 16 individuals with amusia
compared with 16 controls. The study found a similar reaction in the initial phase
of musical detection. Differences appeared in the later integration phase, precluding
hierarchical processing of music. The rupture of interhemispheric fibers was suggested
as the cause of hemispheric disconnection.[37]
It is important to emphasize that these findings are mostly derived from small cohort
studies, and replication in larger populations remains limited.
Genetic aspects
Studies on the genetic role in amusia have primarily been conducted in the context
of classical Mendelian genetics. There is an increased prevalence of amusia within
families.[37] Monozygotic twins are significantly more likely to share amusia than dizygotic twins.[38] The genetic impact appears more pronounced in deficits related to pitch and melody
recognition, while rhythm recognition relies more on environmental factors.[38] A single study indicated a possible association of amusia with a specific mutation,
the deletion of the 22q11.2 chromosome region. This same deletion has been described
in psychiatric diagnoses, but in the same study, amusia was not associated with psychiatric
disorders, suggesting an independent role of this gene in the determination of amusia
and psychiatric disorders.[37] It is important to note that most studies addressing the genetic basis of congenital
amusia are observational in nature and involve limited sample sizes, which may restrict
the generalizability of their findings. Also, although these findings are of interest
in understanding the neurobiological basis of amusia, their clinical utility remains
limited at present since most studies are exploratory, involve small or specific populations,
and lack replication in broader cohorts. Therefore, their use in clinical practice
is not currently supported.
Acquired disorders
Acquired amusia
Musical aphasia is a specific condition in which both language and music are affected
due to brain damage, usually in the left hemisphere, particularly in the Broca's or
Wernicke's area. Musical aphasia involves deficits in processing rhythm and melodic
structures, impairing musical understanding similarly to how language is affected.
It mainly impacts rhythm perception and melodic structure, as the areas responsible
for language, usually in the left hemisphere, also play a role in rhythm and structural
processing in music.[39]
The most well-known case of amusic aphasia occurred with Maurice Ravel (1875–1937),
the renowned French composer, conductor, and pianist. In 1927, Ravel began showing
symptoms of dementia, with memory and language impairments, ideomotor apraxia, and
amusia, which, more than his other deficits, prevented him from continuing his musical
activities.[40]
Musical aphasia
Acquired amusia occurs when a person loses the ability to perceive or produce music
accurately due to brain injury, without impairing language. Unlike musical aphasia,
acquired amusia can occur after isolated lesions in the right hemisphere, which is
essential for processing musical characteristics, such as tonality, timbre, and tonal
structure. The main causes are right hemisphere stroke affecting the superior temporal
gyrus and adjacent areas, frontotemporal dementia affecting the right temporal lobe,
and traumatic brain injury.[39]
Absolute pitch
Absolute pitch is a form of musical perception abnormality opposite to amusia, as
it is characterized by the rare ability to identify and name pitches without any reference.
Neurofunctional and genetic studies have investigated the mechanisms and hereditary
bases of this ability.
Neural correlates
Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET)
studies show that absolute pitch is associated with greater activation in the superior
temporal gyrus, particularly in the primary auditory area and adjacent regions.[41]
There is evidence that individuals with absolute pitch exhibit higher connectivity
between the hemispheres, especially through the corpus callosum, facilitating communication
between auditory and memory areas. This increased connectivity may help explain why
these individuals can automatically associate specific sound frequencies with stored
musical pitch representations in memory.[42]
Another finding from imaging studies is a larger volume of gray matter in the auditory
areas of the left hemisphere in absolute pitch. Structural changes, associated with
early training in genetically predisposed individuals, may be related to the ability
to identify musical notes with above-average precision.[38] These conclusions are mostly based on cross-sectional imaging studies with selected
groups of musicians.
Genetic and environmental factors
Genetic studies on absolute pitch indicate a significant hereditary influence. The
prevalence of absolute pitch is much higher in families with a musical background.
Moreover, monozygotic twins have a significantly higher concordance for absolute pitch
compared with dizygotic twins, indicating a genetic component.[43]
Among candidate genes, AVPR1A, located on chromosome 12, is one of the most studied. This gene is associated with
traits such as musical memory and tuning ability, and its expression is considered
a potential influencer of absolute pitch.[44] Whole-genome expression studies also identified other genes or chromosome regions
associated with musical aptitude: SLC6A4 (17q11.2), GALM (2p22), PCDH7 (4p15.1), GATA2 (3q21.3), FOXP2 (implicated in auditory processing), COMT (catechol-O-methyltransferase), SRGAP2 (involved in neural connectivity and synaptic development), and possibly other genes
implicated in neural plasticity and memory.[45] Although genetic associations have been explored in the context of absolute pitch,
their current clinical applicability is limited. These findings are based on studies
with small sample sizes and often lack replication, which restricts their interpretative
value and prevents their translation into clinical or diagnostic use.
The development of absolute pitch also appears to depend on environment and early
training. Children who begin musical training before the age of 7 are more likely
to develop absolute pitch.[46] While early musical training increases the chances of developing absolute pitch,
experiments show that adults can also learn and improve their pitch perception, sustainably
enhancing their ability to correctly identify pitches.[47]
MUSIC, EPILEPSY, AND MUSICAL SEIZURES
MUSIC, EPILEPSY, AND MUSICAL SEIZURES
There is a complex relationship between music and epilepsy, including musicogenic
epilepsy, in which music acts as a trigger for epileptic seizures. Additionally, the
perception of music can also be an auditory manifestation during focal seizures.[48] Another aspect that has been explored is whether passive exposition to music, due
to its effects on brain wave patterns, might have a therapeutic effect on epilepsy.
Although some studies have shown potentially favorable results, there is limited and
low-quality evidence on the antiepileptic effect of music exposition.[49]
Musicogenic epilepsy
This term was first used by Critchley in 1937 to describe focal-onset seizures, with
or without altered consciousness, following exposure to music. Music is a rare trigger
of seizures, and musical stimuli does not necessarily need to be heard; sometimes,
merely thinking about a piece of music can provoke seizures. The latency between the
stimulus and the seizure varies from seconds to several minutes. Some patients develop
seizures upon hearing a specific musical piece while others report seizures triggered
by a particular musical genre, instrument, or composer. Some patients also report
that specific timbres cause seizures.[50]
Functional imaging studies have shown fronto-occipital and fronto-orbital activation
at the onset of the ictus, possibly reflecting an activation of emotions and memories.
Invasive electroencephalographic recordings have shown activity in the right medial
temporal lobe, extending to the lateral temporal lobe, Heschl's gyrus, the insula,
and areas of the frontal lobe.[51]
It is unclear whether music triggers seizures by directly affecting auditory cortex
brain activity or if the emotional and cognitive components evoked by listening to
music initiate the seizure.[48] Although the precise mechanism by which music acts as a trigger is not yet fully
understood, a complex interaction between auditory processing circuits and the brain's
emotional networks in surely involved.[52]
[53] The current evidence is based primarily on case reports and small case series.
In recent years, some cases of musicogenic epilepsy have been associated with the
presence of autoantibodies against glutamic acid decarboxylase 65 (GAD) with or without
associated limbic encephalitis. The use of immunosuppressive medication has been associated
with improvement in some of these reported cases.[54]
[55]
Musical seizures as epileptic manifestations
Musical seizures are those in which the symptoms are related to the perception of
music and they can have different forms, including positive phenomena such as musical
hallucinations, intense desire for music, ictal singing, whistling, and murmuring;
or negative phenomena such as transient aprosody or amusia.[49] When causing positive phenomena, the manifestation is referred to as musical hallucination.
Although epilepsy is one of the causes of musical hallucination, there are other more
frequent etiologies, as will be discussed in the following section.[56] Musical hallucinations in the context of epilepsy can be divided into three subtypes,
comprising ictal, post-ictal, and inter-ictal phenomena. EEG and fMRI studies show
that epileptic musical hallucinations arise from within the auditory network.[56]
Other manifestations of musical seizures are even rarer than musical hallucinations.
Ictal singing localization may vary, with some patients presenting frontal lobe and
others temporal lobe onset. Singing can represent a form of automatism of a learned
motor pattern. There are few reported cases of ictal whistling. The lateralization
is not precisely defined, but the location is generally in the temporal lobe.[57]
MUSICAL HALLUCINATIONS
Phenomenology and epidemiology
Musical hallucinations are a particular type of auditory hallucination in which the
patient hears music, being aware of the hallucinatory nature of the perception. Unlike
other auditory hallucinations, such as voices, these hallucinations involve well-structured
and familiar music. Evidence in this area is heterogeneous, with some findings based
on retrospective case reviews and others derived from imaging studies in individual
patients.
Musical hallucinations predominantly affect elderly individuals with hearing loss.[58] Despite their musical content, these hallucinations can be very disturbing. More
than two thirds of published cases were in women, and in nearly one third, there was
a structural brain lesion.
Etiologies of musical hallucinations
Hearing loss
Hearing loss is the most frequent cause of musical hallucinations. It was suggested
that patients with inner ear lesions may develop a hyperactive state of the ear.[59] Another possible explanation is that due to the absence of external stimuli the
brain creates internal sounds, leading to the perception of non-existent melodies.
This phenomenon is comparable to what occurs in people with vision loss, who may experience
visual hallucinations, known as Charles Bonnet syndrome. Music hallucinations in patients
with hearing loss have been designated as auditory Charles Bonnet syndrome.[60] Treating the hearing impairment can yield significant improvement of music hallucinations.
Coping strategies (e.g., more acoustic stimulation) are frequently helpful. Pharmacological
treatment can also be successful, with antidepressants being possibly the more helpful
drug category for this condition.[61]
Psychiatric disorders
Musical hallucinations can occur in patients with psychiatric disorders, such as schizophrenia,
bipolar disorder, and severe depression. In these contexts, hallucinations may occur
as part of a broader symptom profile, often accompanied by other types of auditory
hallucinations, such as voices. The music in these cases may have emotional significance
or be associated with specific memories, which intensifies the hallucinatory experience.[62]
Medication and substance use
The use of certain medications, such as antidepressants, antipsychotics, and benzodiazepines,
can trigger musical hallucinations in some individuals. The cause of the association
between these substances and musical hallucinations is unknown. These rare reports
generally involve individuals over 60 years of age. Interestingly, recreational use
of hallucinogenic substances has not been specifically associated with musical hallucinations,
possibly due to the more severe nature of the hallucinatory states they induce.[62]
Brain lesions
Lesions in brain regions involved in auditory and memory processing can lead to musical
hallucinations. In most described cases, the lesion was in the right hemisphere. Most
brain lesions were vascular or tumoral.[58]
[63]
[64]
MUSICAL MEMORY AND COGNITION
MUSICAL MEMORY AND COGNITION
The relationship between musical perception and other cognitive processes is still
not fully understood. The situations presented below suggest that musical perception,
in both its cognitive and emotional aspects, may have singular aspects when compared
with other types of information processing.
Role of the hippocampus
The role of the hippocampus in musical memory is still under debate. Some reports
on professional and amateur musicians with amnesic syndromes have shown a surprising
preservation of musical memory despite extensive bilateral damage to the medial temporal
lobe structures, including the hippocampus. However, these findings could reflect
the effects of lifelong musical training.[64]
A more recent report described a patient with almost no prior musical training who
suffered bilateral hippocampal lesions, with no damage to other brain regions, resulting
in a severe amnesic syndrome with difficulties in recognizing visual and verbal information.
Even so, this patient maintained musical memory integrity, preserving perception of
tones, melodic contours, intervals, rhythm, and meter. This report suggests an independence
of musical memory and recognition networks.[65]
Functional neuroimaging studies support this hypothesis, showing that the consolidation
of melodic information may occur independently of the hippocampus, unlike memory for
non-musical content.[66] Other studies demonstrate different hippocampal recruitment during stimuli involving
musical recognition memory compared with verbal memory stimuli.[67] Clinical and neuroimaging data support the idea that musical recognition memory
is a cognitive ability that operates largely independently of networks involved in
other memory domains, potentially involving specific brain areas or even other regions
within the hippocampus.[68]
Musical memory in Alzheimer's disease
Several studies have shown that patients with Alzheimer's disease (AD) may preserve
the ability to play or sing music learned before the onset of dementia, despite severe
dementia symptoms, even no longer remembering the music's title or the composer's
name.[68]
[69] Other studies have sought to understand the mechanisms responsible for preserving
musical memories in AD patients. These studies have shown that musical episodic memory
is as affected as verbal episodic memory in AD patients; however, semantic musical
memory is disproportionately preserved. These results are derived from studies involving
small cohorts of patients with AD but consistently shown that, from the early stages,
there are deficits in episodic musical memory but with largely preserved semantic
musical memory.[70]
[71]
[72]
Structural and functional neuroimaging studies have helped to explain these differences,
showing that brain regions involved in encoding long-term musical memory and the degeneration
pattern in AD, showing no overlap between more degenerated areas and those of long-term
musical memory encoding. The most involved areas in long-term musical memory were
the SMA and cingulate gyrus, which are minimally damaged in AD patients.[73] Other studies showed that listening to long-known music generates extensive activation
in prefrontal regions, emotion-related areas, motor, auditory, and subcortical regions
(cerebellum, putamen, limbic structures). Some of these regions are relatively preserved
in AD, at least in the first stages of the disease. In contrast, listening to recently
known music generates much less extensive activation of these areas, providing clues
about why long-term musical memory, but not short-term musical memory, is relatively
preserved in AD.[74]
[75]
Opportunities for music-based therapy
Music-based interventions, particularly neurologic music therapy (NMT), have emerged
as promising tools in the field of neurorehabilitation. Neurologic music therapy utilizes
rhythm, melody, and harmony to engage neural networks involved in motor coordination,
cognitive processing, and speech production. Among its various applications, music
therapy has shown relevance in the management of AD, as it serves as a non-pharmacological
adjunct aimed at enhancing quality of life and alleviating neuropsychiatric symptoms.
A growing body of evidence suggests that musical engagement can improve mood, reduce
agitation, and promote social interaction in individuals with AD. Additionally, musical
activities have demonstrated potential benefits in domains such as language function
and autobiographical memory retrieval—areas commonly affected by the disease.[76]
The therapeutic value of music in AD is supported by neurobiological findings, indicating
that music activates brain regions—such as the medial prefrontal cortex and parts
of the limbic system—that are among the last to undergo degeneration, offering a neuroanatomical
basis for its integration into cognitive rehabilitation. Furthermore, music therapy
may induce neuroplastic changes, fostering functional reorganization and the maintenance
of residual cognitive abilities. A 2023 systematic review evaluating the effects of
music therapy in AD reported that seven out of the eight studies included found significant
cognitive improvements, with active musical interventions outperforming passive listening
in enhancing orientation, language, memory, and emotional wellbeing.[77] Notably, interventions that incorporated music aligned with patients' personal preferences
yielded superior outcomes.[77] Despite these promising results, further research with standardized protocols and
validated outcome measures is essential to consolidate the role of music therapy in
clinical practice and facilitate its broader adoption in dementia care.
In conclusion, music perception is a complex neurocognitive function that engages
widespread and interconnected brain networks, integrating sensory, emotional, and
cognitive processes.[78] While considerable progress has been made in understanding its neural substrates
and clinical manifestations, several challenges remain. Disorders such as amusia,
musicogenic epilepsy, and musical hallucinations are still underrecognized in clinical
practice, partly due to limited coverage in neurology and psychiatry training. Although
some validated tools for assessing conditions like congenital amusia exist, their
use in educational and clinical settings is minimal.
The present review aims to contribute to addressing this gap by providing a structured
synthesis of current knowledge on music perception and its disturbances, along with
their anatomical and functional correlates. We also highlight areas of uncertainty,
including conflicting findings on the neural basis of emotional responses to music
and the limited reproducibility of genetic associations, such as those involving absolute
pitch. Furthermore, we propose key directions for future research, including the development
of standardized diagnostic instruments and prospective studies—particularly focused
on musical memory in neurodegenerative diseases like AD, in which music-based interventions
show therapeutic potential.
By bridging neuroscience, clinical observation, and rehabilitation, music emerges
not only as an object of scientific inquiry but also as a potential tool for enhancing
diagnostic insight and improving patient care. A deeper integration of this knowledge
into medical education and practice may promote a more comprehensive and humanized
approach to neurological and psychiatric disorders.
Bibliographical Record
Renan Barros Domingues, Luísa Aires Domingues, Victor Rebelo Procaci, José Luiz Pedroso.
The neuroscience of music perception: a narrative review. Arq Neuropsiquiatr 2025;
83: s00451811233.
DOI: 10.1055/s-0045-1811233
