Medicine, Nursing and Health Sciences
Investigating the role of the brain in
homeostasis: implications for
physiology in older people
A/Prof Michael Farrell
Department of Medical Imaging & Radiation Sciences
8th September 2015
8th September 2015 2
Interoception
Sensations arising from inside the body
Associated with behaviours and autonomic responses that contribute to
homeostasis
3
Internal Signals
Osmolality of body fluids
Blood Volume
Interoceptive Sensation
THIRST
Behaviour
Search for and ingestion of water
Gratification
“Ah, that’s nice(ish)”
Satiation
Thirst gone
8th September 2015
Research Agenda
Mapping brain networks associated with interoceptive experience and
control of regulatory behaviours
Implicating brain regions in the representation of interoceptive
sensations
– discriminative processes, affective responses, modulation
Investigating interactions between interoception and regulatory
behaviours
Exploring the interplay between interoceptive networks, pathology and
disease expression
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5
Preoptic Nucleus & Thermoregulation
Nakamura Am J Physiol 2011
8th September 2015
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Human Preoptic Anatomy
Koutcherov Y et al. The Journal of Comparative Neurology 2007
8th September 2015
Sweating Activation Pinpoints the PO
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Farrell et al. Temperature 2014
PO Network of Functional Connectivity
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Farrell et al. Temperature 2014
Widely Distributed Networks
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PAIN
Maximum Thirst Post Drink
YOUNG
OLD
x = 8
x = 12
A
HG
FE
DC
B
x = 12
x = 14
2 6Z-score
TEMPERATURE
THIRST
URGE-TO-COUGH
Mazzone et al. Am J Respir Crit Care Med 2007
Cole et al. Brain 2006 Egan et al. PNAS 2005
Farrell et al. PNAS 2008
8th September 2015
Deconstructing Networks: Urge-to-Cough
10 8th September 2015
Stimulus/Response Function
11
Urge-to-Cough Coding
Farrell et al. Neuroimage 2012
8th September 2015
12
Urge-to-Cough Coding
Farrell et al. Neuroimage 2012
8th September 2015
13
Urge-to-Cough Coding
Healthy CHS
Farrell et al. Neuroimage 2012
8th September 2015
Mid Cingulate Cortex & Interoception
14
URGE-TO-COUGH
THERMAL COMFORT
THIRST
Farrell et al. Neuroimage 2012
Farrell et al. J Therm Biol 2011
Farrell et al. PNAS 2008
8th September 2015
Regulatory Behaviours & Autonomic Responses
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COUGH SUPPRESSION SUDOMOTOR ACTIVITY
THERMODEFENSIVE VASOCONSTRICTION “OVER” DRINKING
Farrell et al. Temperature 2014 Mazzone et al. J Neurosci 2011
Saker et al. PNAS 2014
McAllen et al. PNAS 2006
8th September 2015
Coughing Control & Interoception
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Cough Don’t Cough
Capsaicin
Inhaled
Saline
Inhaled A B
C D
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Mazzone et al. J Neurosci 2011
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B + D > A + C
Cough Activation
C + D > A + B
Capsaicin Activation
8th September 2015
Mazzone et al. J Neurosci 2011
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Mazzone et al. J Neurosci 2011
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Mazzone et al. J Neurosci 2011
COUGH
Suppression
Network
8th September 2015
Cough Hypersensitivity = Suppression
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Thirst, Water & Gratification
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Saker et al. PNAS 2014
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Saker et al. PNAS 2014
Water Pleasantness
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Saker et al. PNAS 2014
Water Unpleasantness
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Saker et al. PNAS 2014
Water Unpleasantness/Effort to Swallow
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OVER-DRINKING
8th September 2015
Saker et al. PNAS 2014
Thirst, Satiation and Ageing
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Young, Isotonic
Young, Hypertonic
Old, Isotonic
Old, Hypertonic
Phillips et al. Am J Physiol 1991
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0
1
2
3
4
5
6
0 10 20 30 40 50 60 70 80 90 100 110 120 130
Time (minutes)
Th
irs
t R
ati
ng
(0
-10
)
A
B
C
Hypertonic
Infusion
Access
to water
***
*, *,
1
1.4
1.8
2.2
Vas
op
ress
in (
pg
/mL
)
282
286
290
294
298
Osm
ola
lity
(m
Osm
/kg
)
Young Old
Hypertonic Infusion
Young Old
-2
0
2
4
6
8
10
12
14
16
-10 0 10 20 30 40 50 60 70 80 90 100 110 120 130
Time (minutes)
% S
ign
al
Ch
an
ge
aMCC Young
aMCC Old
B CA
x =12-18
-16
-14
-12
-10
-8
-6
-4
-2
0
2
0 0.2 0.4 0.6 0.8
Volume Water (% body weight)
% S
ign
al C
ha
ng
e
Young
Old
Access
to water
Young Old Overlap
Farrell et al. PNAS 2008
8th September 2015
Conclusions
Widely distributed brain networks code responses to interoceptive
signals in humans
Constituent regions within interoceptive networks fulfill functional roles
in discriminative, affective, cognitive and behavioural processes
The function of interoceptive networks can be influenced by disease
and ageing
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People & Support
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
Monash Uni
Gary Egan
RMH
Lou Irving
David Smallwood
Malcolm Hogg
RII, UTHSCSA
Peter Fox
Jack Lancaster
Angela Laird
GUMC
John VanMeter
Tom Zeffiro
Angior Family Foundation
Sir Edward Dunlop Medical Research Foundation
8th September 2015
