| Pharmaceutical fMRI |
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Friday 24 April 2009 |
| Room 310 |
10:30-12:30 |
Moderators: |
David G. Norris and Alice M. Wyrwicz |
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10:30 |
792. |
Striatal Dopamine Correlates Brain Activation in
Precuneus and Thalamus: A PET-FMRI Study |
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Dardo Tomasi1,
Nora D. Volkow2,3, Ruiliang L. Wang1,
Frank Telang1, Gene-Jack Wang1,
Joanna S. Fowler1
1Medical Department, Brookhaven National
Laboratory, Upton, NY, USA; 2National
Institute on Drug Abuse, National Institute on
Health, Bethesda, MD, USA; 3National
Institute on Alcohol Abuse and Alcoholism, National
Institutes of Health, Bethesda, MD, USA |
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Dopamine (DA) is
implicated in the modulation of attention but its
specific role is not well understood. Here we
assessed the relationship between DA markers [DA D2
receptors (D2R) and transporters (DAT)] in the
striatum with PET and brain activation during a
parametric visual attention (VA) task (measured with
BOLD-fMRI) in healthy controls. Increased DAT and
D2R availability in striatum were associated with
higher activation of the precuneus (BA 7) and the
thalamus. Thus, this study suggests that the DA
mesostriatal pathways facilitate attention by
modulating the activation of regions in the alerting
and orienting pathways of attention. |
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10:42 |
793. |
Caffeine's Effects on
Resting-State Oxygen and Glucose Metabolism: A
Combined MR and PET Study |
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Yufen Chen1,
Andrew B. Newberg2, Jiongjiong wang1,
Hengyi Rao1, Hongyu An3, Joel
Greenberg4, Nancy Wintering2,
Victoria Tolles2, John A. Detre1
1Center of Functional Neuroimaging, University
of Pennsylvania, Philadelphia, PA, USA; 2Department
of Radiology, University of Pennsylvania,
Philadelphia, PA, USA; 3Department of
Radiology, University of North Carolina, Chapel
Hill, NC, USA; 4Department of Neurology,
University of Pennsylvania, Philadelphia, PA, USA |
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Caffeine is an adenosine
antagonist which affects both blood flow and neural
activity. It has been suggested that caffeine could
alter the coupling between cerebral blood flow and
metabolism. In this study, a combination of FDG-PET
and ASL was used to study how caffeine affects
resting-state blood flow, glucose and oxygen
metabolism. The results show caffeine alters the
balance of oxygen and glucose metabolism by
significantly decreasing glucose metabolic rate.
This change was especially prominent in the anterior
cingulate, which may explain how caffeine affects
alertness. |
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10:54 |
794. |
fMRI of Cocaine
Self-Administration in Non-Human Primates |
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Ji-Kyung Choi1,
Helen Deng1, Wim Vanduffel1,
Joseph B. Mandeville2
1Massachusetts General Hospital, USA; 2Radiology,
Massachusetts General Hospital, Charlestown, MA, USA |
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A model of drug
self-administration (SA) in non-human primates (NHP)
was developed for fMRI to enable longitudinal
studies of addiction that assess both the direct
effects of cocaine and the neural correlates of
drug-seeking behavior. NHP (n=2) were trained to
self-administer micro-injections (0.015 mg/kg
cocaine) by fixation to a color-coded cue. The
timing of the SA paradigm separated 1) responses to
drug cues, 2) periods of drug availability, and 3)
the direct effects of cocaine. Results showed
function inhibition in basal ganglia due to cocaine,
and activation of prefrontal cortex associated with
cocaine availability. |
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11:06 |
795. |
Effects of Low-Dose
Sevoflurane on Regional CBF and BOLD Responses to
Auditory Stimulation of Varying Rate and Volume |
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Maolin Qiu1,
Ramachandran Ramani2, Vivien Rekkas1,
Nallakkandi Rajeevan1, Fuyuze S. Tokoglu1,
Robert Todd Constable1,3
1Diagnostic Radiology, Yale University, New
Haven, CT, USA; 2Anesthesiology, Yale
University, New Haven, CT, USA; 3Biomedical
Engineering, Yale University, New Haven, CT, USA |
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Task-induced neuronal
activity in the presence of general anesthesia is
the result of two counteracting factors: the
anesthetic and the task. The former is supposed to
suppress neuronal activity in general, while the
latter is commonly used in fMRI and usually
stimulates focal neuronal activity. It has been
demonstrated in a limited number of animal models
that the total amount of energy consumed by neurons
or the level of neuronal activity in the
sensorimotor region must reach the same level
regardless of how deep the animal was anesthetized
in order to accomplish certain task. However this
result has not been observed in humans where the
auditory and visual regions were examined in the
presence of 0.25 MAC sevoflurane. Among many
differences between these experiments, several
issues remain to be clarified: e.g., will the
strength of the functional stimulus affect the
outcome? Will a strong functional stimulus dominates
the observed changes in neuronal activity by
emphasizing the primary projection against secondary
associations? How the level of anesthesia affects
the observation? Here we report the results from the
study designed and conducted to address these
issues. |
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11:18 |
796. |
How Antidepressants Work: SSRI
Treatment Induces Adaptive Changes in Brain 5-HT
PhMRI Responses |
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Darragh Downey1,2,
Karen E. Davies1, Shane McKie2,
Gabriella Juhasz2, Ian M. Anderson2,
Mark A. Smith3, John-Francis William
Deakin2, Steve R. Williams1
1Imaging Science and Biomedical Engineering,
University of Manchester, Manchester, UK; 2Neuroscience
and Psychiatry Unit, University of Manchester,
Manchester, UK; 3 Astra Zeneca R&D, Astra
Zeneca U.S., Wilmington, DE, USA |
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The delayed therapeutic
effect of SSRIs may be mediated by adaptive changes
to the 5-HT system following chronic treatment.
Desensitisation of the 5-HT system may be observed
by BOLD signal changes directly at the site of
reuptake inhibition or upstream on integrated
networks. Using citalopram challenge phMRI we
examined BOLD responses to the acute and chronic
effects of citalopram. Significant signal decreases
following chronic treatment were found in brain
areas implicated in depression and its treatment. We
observed adaptive changes to an acute
pharmacological challenge suggesting down regulation
of receptor expression or enhanced post synaptic
signalling following chronic SSRI treatment. |
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11:30 |
797. |
Face Processing and 5-HT:
Chronic Citalopram Treatment on BOLD Responses |
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Karen Elizabeth
Davies1, Darragh Downey1,2,
Shane McKie2, Gabriella Juhasz2,
Ian Anderson2, Mark A. Smith3,
John-Francis William Deakin2, Stephen
Ross Williams1
1Imaging Science & Biomedical Engineering,
University of Manchester, Manchester, UK; 2Neuroscience
and Psychiatry Unit, The University of Manchester,
Manchester, UK; 3Research & Development,
Astra Zeneca, Wilmington, USA |
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Serotonin is involved in
mood disorders and also emotional face processing.
Adaptive changes to 5-HT signalling pathways may
result from sustained drug administration and may
account for the delayed therapeutic effect of SSRIs.
We explored BOLD responses during the processing of
faces following chronic citalopram treatment. We
observed significant signal reductions in
hippocampus, anterior cingulate and prefrontal
cortex when observing faces following 11 days of
treatment. Citalopram augmented responses in the
insula, thalamus and posterior cingulate. These
findings suggest that chronic SSRI use modifies 5-HT
pathways involved in low level processes which may
be involved in treatment response. |
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11:42 |
798. |
Effect of Muscimol on BOLD and
Local Neuronal Activity in Awake Animals |
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Daniil P. Aksenov1,2,
Limin Li1,2, Gheorghe Iordanescu1,2,
Xiaomu Song1,2, Alice Wyrwicz1,2
1Center for Basic MR Research, NorthShore
University HealthSystem, Evanston, IL, USA; 2Feinberg
School of Medicine, Northwestern University,
Chicago, IL, USA |
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Many questions remain
about the relationship between the local cellular
metabolic and hemodynamic changes measured by fMRI
and the underlying neuronal electrical activity. In
this study we examined the effect of neuromediators
on BOLD and neuronal activity. Simultaneous fMRI and
electrophysiological measurements of whisker
stimulation were performed before and after
localized injection of the GABA agonist muscimol
into the somatosensory cortex. The drug injection
affected both neuronal activity and BOLD signal.
However, surprisingly, the large reduction in
single-unit activity produced by muscimol was
accompanied by a relatively small change in BOLD
response in the whisker barrel cortex. |
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11:54 |
799. |
Double-Blind,
Placebo-Controlled, Dose-Response FMRI Trial of
Buprenorphine: Differential Valence of BOLD Response
Modulation to Innocuous and Noxious Stimuli in
Sensory and Striatal Regions |
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Jaymin Upadhyay1,2,
Julie Anderson1,2, Adam J. Schwarz2,3,
Richard Baumgartner2,4, Alexandre Coimbra2,5,
Jaime Knudsen1,2, Ed George2,6,
James Bishop1,2, Sanjay Keswani2,3,
Brigitte Robertson2,7, Rudy Schreiber2,7,
David Bleakman2,3, Richard Hargreaves2,8,
Lino Becerra1,2, David Borsook1,2
1P.A.I.N. Group, Brain Imaging Center,
Department of Psychiatry, McLean Hospital, Harvard
Medical School, Belmont, MA, USA; 2Imaging
Consortium for Drug Development, Belmont, MA, USA;
3Lilly Research Laboratories, Eli Lilly
and Company, Indianapolis, IN, USA; 4Biometrics
Research Department, Merck Research Laboratories,
Rahway, NJ, USA; 5Imaging Department,
Merck Research Laboratories, West Point, PA, USA;
6Department of Anesthesiology and
Critical Care, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, USA; 7Sepracor
Inc., Marlborough, MA, USA; 8Basic
Neuroscience Department, Merck Research
Laboratories, West Point, PA, USA |
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Blood-oxygenation level
dependent (BOLD) functional Magnetic Resonance
Imaging (fMRI) has previously been implemented to
observe how specific therapeutics modulate the acute
brain (CNS) response to noxious and innocuous
stimuli. Buprenorphine (Buprenex) is a mixed opioid
partial agonist and antagonist that has been shown
to have analgesic and antihyperalgesic effects in
humans. In this study, the modulatory effects of two
doses of buprenorphine on the CNS response to
innocuous and noxious stimulation were investigated
with BOLD fMRI. |
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12:06 |
800. |
Regional FMRI Activation in
Response to Visceral Stimulation in Rats with
Amygdala Implants of Corticosterone |
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Jelena Lazovic1,
Anthony C. Johnson2, Brent Myers2,
Rheal Towner3, Beverly Greenwood-Van
Meerveld2
1Biology, California Institute of Technology,
Pasadena, CA, USA; 2University of
Oklahoma Health Sciences Center, Oklahoma City, OK,
USA; 3Oklahoma Medical Research
Foundation, Oklahoma City, OK, USA |
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Individuals affected
with visceral pain often have a history of stressful
experiences and anxiety. The aim of this study was
to detect brain activation in response to visceral
stimulation in the context of increased anxiety,
modeled by amygdala targeted corticosterone
delivery. FMRI was performed during colorectal
distensions (40 and 60 mmHg) in corticosterone or
cholesterol (controls) implanted rats. The
corticosterone implanted rats had substantially more
regions of brain activity for both 40 and 60 mmHg
pressure, and greater activation of nuclei involved
in pain processing and higher cognitive function (amygdala,
hippocampus, entorhinal cortex and cerebellum). |
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12:18 |
801. |
Investigate the Mechanisms of
Anesthetic-Induced Unconsciousness in a Mouse Model
by High-Resolution Manganese Enhanced MRI (MEMRI)
Technique: A Preliminary Study |
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Ping Wang1,
Jason Moore1, Thomas Floyd1,2,
Max Kelz1
1Anesthesiology & Critical Care, University of
Pennsylvania, Philadelphia, PA, USA; 2Neurology,
University of Pennsylvania, Philadelphia, PA, USA |
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Manganese is a useful
contrast agent for MRI of animals, resulting in
enhancement on T1-weighted MRI images. Two emerging
hypothalamic targets with proven ability to affect
arousal state are the median preoptic nucleus, MnPO,
and ventrolateral preoptic nucleus, VLPO.
Depolarization of these two regions is respectively
thought to underlie onset and maintenance of natural
sleep. Our hypothesis is that volatile anesthetics
cause unconsciousness (behavioral hypnosis) by
affecting VLPO and MnPO function. In this
preliminary study, we verified the hypothesis by
high-resolution MEMRI (manganese enhanced MRI)
technique. |
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