Musical Brain, Interneurons in Mental Health, Consciousness and Brain Death

Musical Brain

  • How is music information processed in the brain? – through perception, action, and emotion in the brain
  • When we listen to music our brain is constantly making predictions of what’s coming next in the piece, which actively affects how we feel about the music

Predictive coding of music (PCM)

  • The PCM model states our brain predicts music based on past experience
  • A syncopated rhythm (a shifted beat) creates an unexpected note, causing an error in our prediction → this error may make us tap our foot to adjust to the beat
  • Actively listening to music shapes our emotions and helps us learn
  • Over time, our brain updates its predictions through musical experience
  • Music is useful for studying how the brain predicts and processes information

Constituents of music

  • Melody, harmony (the combination of sounds: chords), rhythm (the structured arrangement of successive sound)
  • Subserved by overlapping but distinct neural networks
  • They interact to create a unique musical experience

Perception of Music: Melody

  • Melody: patterns of pitched sounds unfolding over time
    • Helps define a piece of music and makes it unique
    • Each note has its own pitch, each has a different frequency (Hz)
  • Timbre (tone quality): also known as tone color or tone quality, the perceived quality of a sound, including its spectral composition and its additional noise characteristics

Sankaran et al.’s study

  • Objective: recorded auditory cortex activity while subjects listened to music
  • Key pitch-related features analyzed:
    • Absolute pitch – the exact note played
    • Pitch change – whether the pitch goes up or down
    • Expectation – how predictable a note is, based on an algorithm
  • Findings: identified three distinct neuron groups:
    • Pitch neurons – responded differently to high vs. low notes
    • Pitch change neurons – reacted distinctively to rising vs. falling notes
    • Expectation neurons – distinguished between expected vs. unexpected notes
    • These neuron groups are distributed along the anterior-posterior axis of the auditory cortex.
    • Some notes are more or less expected based on past experiences

Perception of music: Harmony

  • Depending on the harmony played, we perceive the music differently

  • Harmony: the combination of multiple, simultaneously pitches sounds to form a chord, and subsequent chord progressions, a fundamental building block of Western music.

  • The rules of harmony are the hierarchically organized expectations for chord progressions (e.g., C-scale: C-F-G-C)

  • Chords may in themselves give rise to an emotional response

    • C-major: C, E, G perceived happier than C-minor: C, Eb, G by Western listeners

  • Consonance: notes that sound smooth and pleasing together; harmony & stability

    • Perceived as “pleasant” sounding
    • Produces “resolution” (relief) in music when following dissonance

  • Dissonance: notes that sound clashing or tense; sense of instability or suspense, often leading to a resolution

    • Perceived as “unpleasant” sounding
    • Produces “tension” in music

  • Babies prefer consonant sounds

  • In western music, dissonance.consonance comes from specific combinations of gaps (intervals) between two notes (pitches)

  • Auditory cortices showed stronger functional connectivity with the ACC during dissonant portion of the task

  • A choral pierce (chords only – no individual notes to compose a melody) with variations on the chord sequence

  • Consonant chords were used in the “consonant” condition

  • Dissonance was achieved by lowering the pitch of some of the instruments in the consonant condition by 1 semitone

  • The neutral tone bilaterally activated primary auditory cortices compared to silent baseline periods

  • Dissonant variants showed higher activation of the left medial prefrontal cortex (mPFC) and left rostral anterior cingulate cortex (ACC)

    • Linked to their roles in threat processing and evaluation
    • Rostral-ventral regions are involved in emotional tasks
    • Functional connectivity between the auditory cortex and ACC
    • ACC activity can also be related to conflict detection/resolution
    • Observed ACC activity related to listeners attempting to find a tonal center in dissonant variation

Perception of Music: Rhythm

  • Rhythm: the structured arrangement of successive sound events over time, a primary parameter of musical structure. Rhythm perception is based on the perception of duration and grouping of these events.
    • Rhythm can be produced by the onset of the notes in a melody or without a melody
    • The perception of rhythm usually involves the simultaneous perception of evenly spaced pulses and a meter
    • Listening to pulse trans involves prediction of following events
    • Studies show brain responses to omission of a beat or after the end of rhythmic sequences
    • Rhythm perception involves the motor system: the premotor cortex, supplementary motor area, basal ganglia, and cerebellum
      • This activity helps establish and maintain musical pulses and meters
    • Even newborns show rhythmic abilities, and training can shape their perception of duple (2/4) or triple ( 3/4\,3/4) meter
    • Additionally, moving in sync with a beat may encourage prosocial behavior – infants tend to be more helpful after bouncing in rhythm with an experimenter
  • Movement (being bounced every second or third beat by their mother) influences infant rhythm perception
    • They will prefer the rhythm they were bounced to over a new rhythm
    • The infant will be more helpful to an experimenter that bounced with them as opposed to an experimenter that bounced at a different rhythm

Action generation by music

  • Groove and movement
    • Groove is the pleasurable urge to move with music
    • Created by a rhythm section (percussion and bass) that maintains a steady beat with repeating syncopated patterns

Brain processing of groove

  • Groove links perception and movement
  • The brain constantly evaluates prediction errors caused by syncopations
  • Syncopated (characterized by displaced beats or accents so that the strong beats are weak and vice versa) rhythms make us want to move

Why syncopation feels good

  • An inverted U-shaped model suggests that groove is highest at medium syncopation levels

  • Moderate syncopation is the most pleasurable and movement-inducing, while too little or too much diminishes the groove effect

  • Medium syncopation and prediction

    • The brain balances prediction errors and precision at intermediate syncopation levels
    • When rhythms are moderately syncopated, the brain resolves prediction errors by either adjusting expectations or moving the body to match the beat
    • Moving in time helps stabilize our sense of rhythm and reduces sensory mismatches

  • Too little or too much syncopation

    • Low syncopation: predictable beats create few errors, reducing the urge to move
    • High syncopation: the beat becomes too unpredictable, making it harder to process and move along with

  • Why syncopation feels good

    • The drive to move with groove is linked to motor and pleasure networks in the brain
    • Syncopation activates the nucleus accumbens (NAcc) and orbitofrontal cortex, key regions in the reward system that respond to rhythm predictability

  • In summary,

    • The brain optimizes syncopation-related prediction errors to create an enjoyable urge to move
    • The right amount of syncopation allows active engagement with music, making movement feel rewarding

Emotion and Pleasure

  • Music can modulate activity in brain structures that are known to be crucially involved in emotion
  • The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders

Neural correlates of music-evoked emotions

  • Amygdala
    • Regulates and modulates emotions
    • Plays a role in starting, maintaining, and ending emotional responses
    • Integrates cognitive and emotional information
  • Nucleus accumbens
    • Processes pleasure and motivation
    • Drives behaviors to seek and obtain rewards
    • Connected to the auditory cortex during rewarding music experiences
    • Functional connectivity between the nucleus accumbens and auditory cortex/orbitofrontal cortex predicts whether a person will choose to buy a song
  • Hippocampus
    • Linked to both positive (joy) and negative (fear, unpleasantness) emotions
    • Helps regulate stress through the hypothalamus-pituitary-adrenal (HPA) axis
    • Music-evoked joy strengthens the connection between the hippocampus and hypothalamus, potentially reducing stress by lowering cortisol levels

Social functions of music: the seven Cs

  • When individuals make music, the come into contact with each other
  • Music automatically engages social cognition
  • Engaging with music can lead to co-pathy
    • Co-pathy – interindividual empathic states, reducing conflicts and strengthening group bonds
  • Music involves communication
  • Music making also involves coordination of actions
  • A convincing musical performance by multiple players is only possible if it also involves cooperation
  • Music leads to increased social cohesion of a group

Music as therapy

  • Music and brain function
    • Music influences brain regions involved in emotions, memory, and movement
    • Disorders like depression, anxiety, PTSD, Parkinson’s, schizophrenia, and Alzheimer's involve dysfunction in areas such as the amygdala, hippocampus, and cingulate cortex
    • Since music affects these regions, further research could uncover its full therapeutic potential

Music and Autism Spectrum Disorder (ASD)

  • Individuals with ASD struggle with social-emotional interactions but can process emotions in music almost naturally
  • Brain scans show that music activates language-related areas that do not respond to speech in ASD patients
  • Music therapy could help ASD patients develop emotional vocabulary and improve communication and social skills

Music and Neurodegenerative Diseases:

  • Alzheimer’s patients often retain music memory, recalling familiar songs even when other memories fade
  • Learning lyrics through singing may help with word retention
  • Music can reduce anxiety in AD patients
  • Since memory and emotions are linked in the hippocampus, music may help slow cognitive decline and improve emotional well-being

Music for anxiety, pain, and stroke recovery

  • Music helps reduce stress and anxiety
  • It provides some pain relief in clinical settings, though not as effectively as medication
  • Stroke patients who listen to music regularly during early recovery show fewer negative emotions and improved verbal memory and attention
  • These benefits may come from the brain’s neurochemical response to positive emotions in music
  • Future potential: with more research, musical could become a key therapy for improving emotional well-being, cognitive function, and neurological recovery

Interneurons in Mental Health

  • Morphology: shape

  • The cortex is made up of many different layers and the different layers have different functions

  • Parvalbumin (PV) interneurons can be found all throughout the brain but we are focusing on the cortex

    • Chandelier cells: not present in layer four of the cortex
    • Basket cells: target the cell body, present in layers 2-6

  • PV interneurons’ action potentials are way narrower (occur in less time/faster) than excitatory neurons’ action potentials

  • Inhibition makes it less likely the AP will happen (cross the threshold)

  • Inhibition shortens the window that excitatory neurons can sum together to have a staggered AP pattern

  • PV interneurons – gamma oscillations, implicated in schizophrenia, autism

  • PV interneurons have unique properties that allow them to perform key neural computations and influence mental health

  • Barrel cortexes only occur in animals with whiskers. They’re only present in layer four of the cortex

  • Each barrel corresponds primarily to one whisker

  • Intralaminar connections span across the different barrels

  • Interlaminar connections span across the entirety of one barrel

  • Typically info enter the brain through layer 4, and then ⅔, and then 5

  • Thalamus (lemniscal, VPM): layer 4

  • Thalamus (paralemniscal, POm): layer 5

  • Whiskers react more when a whisker touches another animal than when it touches an object

  • Barrel cortex is a complex, functionally-relevant brain region which is well-suited to investigations of PV interneuron circuitry

  • Hybrid Voltage Optical Sensory (HVOS) is a really powerful tool because it allows us to record from many cells simultaneously and optically (really exciting b/c normally you can only measure cells one at a time and not optically)

  • A fluorescent protein tethered inside a cell membrane tells how much activity is going on in the cell membrane via the fluorescent light it emits when activity happens

  • Signal-to-noise ratio (SNR) = amplitude/noise

  • Half-width tells us how narrow (fast) the AP is

  • Conduction velocity: we stimulate the excitatory neuron and it makes the PVIs react in order of which PVI is closer to the cell body of the excitatory neuron

  • Latency: amount of time it take for each section to fire

  • Latency and distance allows us to calculate velocity

  • Interlaminar conduction velocity was 71% faster than intralaminar conduction velocity

  • Interlaminar computations and intralaminar computation have different functions

  • Interlaminar

    • intracortical and thalamic integration
    • Narrow sensory tuning curves
    • Texture discrimination

  • Intralaminar

    • Multiwhisker integration
    • Direction preference

  • Longer rise time in layer ⅔ vs. layer 4

  • Layer ⅔ has higher decay time than layer 4

  • Amplitude, half-width, rise time, decay time are all different based on layer

  • FXRI CKO in the barrel cortex impacts many PV interneurons…

  • Electrophysiological properties of PVIs depend on layer

  • Changes in FXRI expression alter…

  • HVOS has illuminated previously undescribed aspects of PVI electrophysiology

Consciousness and Brain Death

  • Consciousness is generally defined as our subjective awareness of ourselves and our environment
  • Consciousness is functional:
    • It enables us to plan activities, set goals, and monitor our progress toward achieving them
    • It is fundamental to our sense of morality, allowing us to reflect on our actions and intentions
    • However, consciousness can also become aversive in certain situations. For example, when we realize that we are not meeting our own goals or expectations – or when we believe others view us negatively – this awareness can cause psychological distress. In response, some individuals may turn to substances like alcohol or drugs to escape these troubling conscious thoughts.
  • Most psychologists and neuroscientists believe that all mental functions – including consciousness – originate from the brain
    • Monism (Psychoneural Identity Hypothesis)
      • Mind = Brain
      • The mind is not separate from the brain; mental processes arise entirely from physical brain activity
    • Dualism
      • Mind = Brain + ‘X’
      • The mind includes more than just the brain – it involves a non-physical element (often called the “soul”)
  • Tolman & Honzik - insight in rats
    • Training – shortest route, intermediate route, or longest route
    • What happens if you block a certain path? If the shortest route is blocked, most animals took the intermediate route
    • If the block is at the end of the short route, the animal will come back to its starting place; if there’s insight, the animal will not take the intermediate route because it knows the paths are the same and so there will also be blockage; what they see is usually the animal will take the longest route, indicating some kind of insight
    • If consciousness is based on insight, then you could argue that a rodent has some basic level of consciousness
  • Self-awareness tests of consciousness in animals
    • Mirror self-recognition test (MSR) - can an animal recognize itself in a mirror
    • Failed to find evidence that monkeys have self-awareness in the mirror
  • Skinner - positive reinforcement conditioning

Neuronal substrates of consciousness

  • Claustrum (‘hidden away’)
    • Volume is ~0.25% of the cerebral cortex
    • Think, irregular sheet of grey matter that lies just below insula and above putamen
    • Thickness: a fraction of mm to several mm
    • Cells receive inputs and send outputs to various cortices
  • What happens if there’s brain damage to the claustrum?
    • No evidence supporting claustrum’s role in consciousness
    • No subject with bilateral region - potentially a more profound effect, but no evidence with only one hemisphere destroyed
    • If we stimulate it, can we disrupt consciousness function?
      • None of the simulations, even bilateral stimulation, affected or disrupted consciousness
  • Neural correlates (signatures) of consciousness?
    • Consciousness is the result of integrated activity (functionally meaning activity from several brain areas) of the many neural connections in the brain that allows a unifying experience across different sensory and functional modalities
    • Different states (or levels) of consciousness depend on what your brain is currently doing
  • Evidence supporting that different levels of brain activity correlate with consciousness
  • RISE OF THE PLANET OF THE APES!!!! (2011 remake)
    • What are the ethical and scientific implications of creating human-animal brain hybrids?
    • Could enhancing animal brain function through genetic or neurological interventions lead to self awareness?
    • As AI systems become more advanced, is it possible for them to develop consciousness?

Brain Death and Restoration

  • Brain death = human death?
    • Two main components of consciousness: wakefulness and awareness
    • The two components are linearly correlated along the spectrum of consciousness

What Near-Death Experiences (NDEs) Reveal About the Brain

  • A close brush can leave a lasting mental legacy – and may tell us about how the mind functions under extreme conditions (Christof Koch on June 1, 2020)

  • NDEs are triggered during singular life-threatening events such as heart attacks or blunt force injuries from explosions or falls. About one in 10 patients who suffer cardiac arrest in a hospital setting reports an NDE.

  • These experiences often share striking similarities: a sudden absence of pain, visions of a bright light at the end of a tunnel, sensations of floating above one’s body, or even traveling into space. While many NDEs are described as peaceful or uplifting, others are distressing. However, negative NDEs are significantly underreported due to shame, social stigma, and pressure to conform to the popular image of the “blissful” NDE.

  • Why the mind might interpret the body’s desperate attempt to function without blood flow and oxygen as positive and blissful – rather than terrifying – remains a mystery.

  • NDEs may represent a rare and unusual state of human consciousness, made all the more remarkable by the fact that a brief episode, often lasting less than an hour, can lead to a lifelong transformation.

  • High-frequency neurophysiological activity in the near-death state exceeded levels found during the conscious waking state. These data demonstrate that the

  • Advanced neuronal features in t-hCO reveal activity-dependent disease phenotypes in human cortical neurons mammalian brain can, albeit paradoxically, generate neural correlates of heightened conscious processing at near-death.

  • To investigate whether these preclinical findings translate to humans, we analyzed electroencephalogram and electrocardiogram signals in four comatose dying patients before and after the withdrawal of ventilatory support. Two of the four patients exhibited a rapid and marked surge of gamma power, surge of cross-frequency coupling of gamma waves with slower oscillations and increased interhemispheric functional and directed connectivity in gamma bands.

  • Importantly, both patients displayed surges of functional and directed connectivity at multiple frequency bands within the posterior cortical “hot zone,” a region postulated to be critical for conscious processing

  • crPAC: cross-regional phase-amplitude coupling

  • Evidence suggests the dying human brain can be activated

  • If consciousness is the result of integrated activity of the many neural connections in the brain that allows a unifying experience across different sensory and functional modalities, can lab-grown brains become conscious?

  • Restoration of brain circulation and cellular functions hours post-mortem –

    • 32 pig brains were connected to the BrainEx system (4 hours after the pigs had been killed, and after removing the brains from the skulls)
    • Pigs raised for food consumption are exempt from welfare laws governing how research animals are treated

  • People tried to grow human brain cells in animals – human brain organoids

  • Brain organoid – a self-organizing artificially grown mass of human embryonic stem cells that simulate architecture and functionality of the human brain

  • t-hCO neurons undergo advanced maturation (increased size, increase dendritic arborization)

  • Tourette syndrom (TS) – a neurological disorder characterized by sudden, repetitive, rapid, and unwanted movements or vocal sounds called tics

    • Increased dendritic spine density

  • Transplanted hCO receive whisker sensory-related inputs

  • They grow → they respond to somatosensory stimulation

  • Involved in integrating somatosensory information, and behavioral output

  • Transplanted hCO make functional connections onto rat neurons and modulate behavior

    • t-hCO cells can activate rate neurons to drive reward-seeking behaviors

  • If a human-monkey hybrid is possible, it would be some evidence that Darwin is correct

  • Injecting human stem cells into monkey embryos

    • Successful hybrid culture
    • At a certain point, human cell and monkey cell would be integrated – ethical concerns

  • Human accelerated regions are highly conserved DNA sequences with human-specific nucleotide substitutions

    • When these are put into mouse embryos, their cortical areas are larger