Tone deafness: a disorder of the mind’s ear Tim Griffiths Auditory Group, Newcastle University Cognitive Neurology Clinic, Newcastle General Hospital http://www.staff.ncl.ac.uk/t.d.griffiths/tdg.html Supported by the Wellcome Trust (UK)

My work: Ordered and disordered acoustic worlds The Ear The person 2. NEUROLOGY Disordered sound pattern analysis Speech Music Environmental Sound The mind’s ear 1. NEUROSCIENCE Ordering of sound pattern

How do we explain this? Click picture for sound

Famous subjects with tone deafness Che Guevara Milton Friedman

Tone deafness: some basic questions His brain? His DNA? His neurons? His deficit?

Tone deafness: clues from neuroscience Disorder in the pitch domain: music assessments show input problem with melody perception What is pitch? How does the brain analyse pitch and pitch patterns?

Disorder in the pitch domain: music assessments show input problem with melody perception

What is pitch?

How does the brain analyse pitch and pitch patterns?

Pitch: normal mechanisms Most neuroscience text books are wrong, and so was von Helmholtz It’s not frequency Pitch is a percept not a stimulus property

Most neuroscience text books are wrong, and so was von Helmholtz

It’s not frequency

Pitch is a percept not a stimulus property

Pitch: normal mechanisms von Helmholtz On the sensation of tone (1862)

von Helmholtz

On the sensation of tone (1862)

Construction of the pitch percept 400Hz sine 400Hz fundamental Harmonic 1 - 6 400Hz fundamental Harmonic 4 - 6 frequency (kHz) time (s) frequency (kHz) frequency (kHz) time (s) time (s) 5 5 5 0.1 0.1 0.1 Common pitch explained better by time structure than frequency structure of stimulus

Pitch representation in the cortex Functional imaging studies where brain activity measured when time structure of sound and associated pitch strength are varied

Functional imaging studies where brain activity measured when time structure of sound and associated pitch strength are varied

Individual data: Structural MRI Scan

noise - silence fixed pitch – noise Individual fMRI data: Pitch Activation Griffiths et al Nature Neurosci 1998, 2001 Patterson et al Neuron 2002

Neural activity corresponding to the pitch of individual notes occurs in secondary auditory cortex Accumulating evidence that activity in this area correlates with the perception of the pitch of sound and is not just a representation of the stimulus Analogy to colour area in visual brain where perceived colour not stimulus wavelength represented A ‘pitch centre’ in the auditory cortex?

Neural activity corresponding to the pitch of individual notes occurs in secondary auditory cortex

Accumulating evidence that activity in this area correlates with the perception of the pitch of sound and is not just a representation of the stimulus

Analogy to colour area in visual brain where perceived colour not stimulus wavelength represented

Pitch sequences in the cortex

noise - silence fixed pitch – matched noise ‘ lively’ pitch – fixed pitch NB NO TASK Individual fMRI data: Pitch sequence Griffiths et al Nature Neurosci 1998, 2001 Patterson et al Neuron 2002

PET group data: Pitch sequence NB TASK Griffiths et al Neuroreport 1999

Pitch sequences in the cortex Distributed networks beyond auditory cortex For very high level processing (tonality) frontal processing only: no specific involvement of auditory cortex

Distributed networks beyond auditory cortex

For very high level processing (tonality) frontal processing only: no specific involvement of auditory cortex

Pitch: studies of stroke patients Summary data Stewart et al Brain 2006

Tone deafness: clues from neuroscience Normal functional imaging and studies of stroke patients broadly congruent Analysis of the pitch of individual notes involves a pitch centre in secondary auditory cortex Highly distributed networks for pitch sequence analysis beyond auditory cortex If the deficit in melody perception in tone deafness is due to abnormal pitch pattern analysis, it is likely to be a problem with cortex beyond primary cortex

Normal functional imaging and studies of stroke patients broadly congruent

Analysis of the pitch of individual notes involves a pitch centre in secondary auditory cortex

Highly distributed networks for pitch sequence analysis beyond auditory cortex

If the deficit in melody perception in tone deafness is due to abnormal pitch pattern analysis, it is likely to be a problem with cortex beyond primary cortex

Tone deafness: what is the pitch deficit? Pitch change and pitch direction analysis Foxton et al Brain 2004 Pitch Change 1 Pitch Change 2 Pitch DIRECTION

Tone deafness: what is the pitch deficit? Abnormal perception of pitch direction ‘ Bottom up’ basis for melody deficit: musicology Deficient memory ‘trace’ for pitch –subjects unable to ‘keep track’ of pitch?

Abnormal perception of pitch direction

‘ Bottom up’ basis for melody deficit: musicology

Deficient memory ‘trace’ for pitch –subjects unable to ‘keep track’ of pitch?

Tone deafness: Brain structure 1 White matter density: Montreal and Newcastle structural MRI data Hyde, Zatorre, Griffiths, Lerch and Peretz Brain 2006

Tone deafness: Brain structure 2 Cortical thickness: Montreal and Newcastle structural MRI data Hyde, Lerch, Zatorre, Griffiths, Evans, Peretz (Human Brain Mapping Meeting 2006)

Decreased white matter in right inferior frontal lobe Increased cortical thickness in right inferior frontal lobe and right auditory cortex Single-gene basis for both findings possible (connectivity deficit due to axonal migration disorder or cortex neuronal migration disorder) Tone deafness: brain structure

Decreased white matter in right inferior frontal lobe

Increased cortical thickness in right inferior frontal lobe and right auditory cortex

Single-gene basis for both findings possible (connectivity deficit due to axonal migration disorder or cortex neuronal migration disorder)

Tone deafness: genes? Family undergoing genetic analysis in Newcastle Stewart , McDonald, Kumar, Chinnery, Griffiths (Music and Genetics Meeting Bologna 2007 ) Proband Family

Single gene explanations unlikely to be universal explanation for tone deafness Analogy with early onset Alzheimer’s disease (rare single-gene families and more common genes of major effect)? Tone deafness : genes?

Single gene explanations unlikely to be universal explanation for tone deafness

Analogy with early onset Alzheimer’s disease (rare single-gene families and more common genes of major effect)?

Apart from occasional disturbances of the peace, sufferers are generally useful members of society Model system where we have the potential to explain a complex behaviour in terms of abnormal cortical development and connectivity Other examples of disorders where abnormal connectivity implicated: schizophrenia, autism Tone deafness: who cares?

Apart from occasional disturbances of the peace, sufferers are generally useful members of society

Model system where we have the potential to explain a complex behaviour in terms of abnormal cortical development and connectivity

Other examples of disorders where abnormal connectivity implicated: schizophrenia, autism

Acknowledgements: Current (previous) group members and collaborators Newcastle Auditory Group: Simon Baumann: Freya Cooper; (Jessica Foxton); Manon Grube; (Amanda Jennings); Katharina von Kriegstein; Sukhbinder Kumar; Tobias Overath; (Lauren Stewart) Wellcome Centre for Imaging Neuroscience: Ray Dolan; Richard Frackowiak; Karl Friston Cambridge University (CNBH): Roy Patterson Montreal (BRAMS): Krista Hyde; Isabelle Peretz, Robert Zatorre

Newcastle Auditory Group:

Simon Baumann: Freya Cooper; (Jessica Foxton); Manon Grube; (Amanda Jennings); Katharina von Kriegstein; Sukhbinder Kumar; Tobias Overath; (Lauren Stewart)

Wellcome Centre for Imaging Neuroscience:

Ray Dolan; Richard Frackowiak; Karl Friston

Cambridge University (CNBH): Roy Patterson

Montreal (BRAMS): Krista Hyde; Isabelle Peretz, Robert Zatorre