Medicine, Nursing and Health Sciences

Cough hypersensitivity is associated

with activation in the midbrain

A/Prof. Michael Farrell

Department of Medical Imaging & Radiation Sciences

16th August 2014

16th August 2014 2

Cough and the Urge-to-Cough

Most common reason to seek medical attention (McGarvey & Morice Respir

Physiol Neurobiol 2006)

Persistent, unproductive coughing is a common problem (Ford et al. Thorax

2010)

Lots of money is spent on anti-tussives that have questionable benefits (Dicpinigaitis Br J Pharmacol 2011)

An urge-to-cough can precede coughing and is distressing when not

satiated by coughing

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Cough Hypersensitivity Syndrome (CHS)

• Laryngeal Parasthesia (abnormal throat sensation)

• Hypertussia (increased cough sensitivity in response to known triggers)

• Allotussia (cough triggered by non-tussive stimuli)

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Cough Hypersensitivity Syndrome (CHS)

• Laryngeal Parasthesia (abnormal throat sensation)

• Hypertussia (increased cough sensitivity in response to known triggers)

• Allotussia (cough triggered by non-tussive stimuli)

Zambreanu et al. 2005 Pain 114(3):397-407

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Cough Hypersensitivity Syndrome (CHS)

• Laryngeal Parasthesia (abnormal throat sensation)

• Hypertussia (increased cough sensitivity in response to known triggers)

• Allotussia (cough triggered by non-tussive stimuli)

Zambreanu et al. 2005 Pain 114(3):397-407

Are tussive-related regional brain responses

amplified in people with CHS?

Are there brain regions that show decreased

tussive-related activation in CHS patients

compared to controls?

Is there tussive-related regional brain

activation that is unique to people with CHS?

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Urge-to-Cough-Functional Neuroanatomy

McGovern et al. Neuroscience 2012

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Urge-to-Cough-Functional Neuroanatomy

Mazzone et al. AJRCCM 2007

AI Agranular Insula

DI Dysgranular Insula

GI Granular Insula

LO Lateral Orbital Cortex

S1 Primary Somatosensory Cortex

S2 Secondary Somatosensory Cortex

McGovern et al. Neuroscience 2012

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Cough Hypersensitivity Patients

*

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Decreased thresholds for the urge-

to-cough and to elicit coughing

Increased ratings of urge-to-cough

at equivalent doses of capsaicin

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Stimulus Intensity Coding Healthy

CHS

High Dose > Low Dose

Farrell et al. Neuroimage 2012

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Urge-to-Cough Coding

Farrell et al. Neuroimage 2012

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Urge-to-Cough Coding

Farrell et al. Neuroimage 2012

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Urge-to-Cough Coding

Farrell et al. Neuroimage 2012

Healthy CHS

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Suppression Network

Mazzone et al. J Neurosci 2011

Healthy Controls

Healthy Controls > HCS

Farrell et al. Neuroimage 2012

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CHS – Unique Midbrain Activation

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CHS – Unique Midbrain Activation

Nucleus Cuneiformis

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CHS – Unique Midbrain Activation

*

*

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CHS – Unique Midbrain Activation

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Conclusions

• The urge-to-cough is represented in a distributed brain network

incorporating functional subunits that code stimulus attributes, represent

sensory experience and control motor responses

• Brain regions coding airway stimulus intensity and urge-to-cough show

enhanced responses in patients with CHS

• Cough suppression-related activation in the ventromedial prefrontal

cortex and anterior cingulate cortex is impaired in patients with CHS

• Midbrain activation in CHS patients during capsaicin activation may

contribute to the modulation of afferent inputs from the airways

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Acknowledgements People

FINMH

Interoception Imaging

Leonie Cole

Pascal Saker

Ayaka Ando

Jennifer Leech

Camille Shanahan

Neurobiology

Derek Denton

Michael McKinley

Robin McAllen

David Trevaks

UQ

Stuart Mazzone

Alice McGovern

RMH

Lou Irving

David Smallwood

Malcolm Hogg

Monash U

Gary Egan

RII, UTHSCSA

Peter Fox

Jack Lancaster

Angela Laird

GUMC

John VanMeter

Tom Zeffiro

Support

Angior Family Foundation

Sir Edward Dunlop Medical Research Foundation