Transcript 4 Darren

An fMRI Study of the Effect of
Amphetamine on Brain Activity
Stephen Uftring, Stephen Wachtel, David Chu, Cyrus
McCandless, David Levin & Harriet de Witt (2001)
Background
• fMRI can be used to study the
specific neural actions of drugs
of abuse (Klein-schmidt et al., 1999)
• fMRI documents change in
neural activity due to a drug;
alone or in concert with a task
• Amphetamines may increase
activity in specific brain regions
(Maas et al., 1998; Daniel et al., 1991)
• Low doses (5-10 mg) improve
auditory performance without
affecting motor performance
•
(Koelega, 1993; Bye et al., 1973)
Higher Doses?
Aim
• Effects of 20 mg of d-amphetamine
on brain activity and behavior, while
engaging in an auditory and a motor
task
Subjects
• Ten healthy adult right-handed
males (Edinburgh Handedness
Inventory Test)
• Exclusion criteria
1.
Any current Axis 1 disorder
2. History of a substance use disorder
3.
History of drug dependence or abuse
Procedure
• Abstain from all drug use for 24
hours prior to session
• Ss tested for drug use
• For blinding, Ss told that they may
receive either an amphetamine or a
placebo
• Two-session, cross-over design
Physiological and Subjective
Effect Measures
• Blood pressure, heart rate
• Collected before ingestion of
amphetamine or placebo and hourly
for four hours after ingestion
• Drug Effects Questionnaire
fMRI Protocol
• 1.5 T MR
• 3D T1 anatomic map
• Superimposed activation maps
onto anatomical map
Tasks
• 2 hrs. after ingestion, Ss
underwent fMRI imaging, while
performing auditory and motor
tasks
• Auditory task: Tone Decision
(TD) task
• Motor task: Finger Tapping (FT)
task
Boxcar Paradigm
5 x 50 sec task periods alternating with 5 x 50 sec
control periods
t(sec) 0 50 80 130 180 260 340 420 500
580 660 740
•Data collection started 10 seconds after S started task
•Task and control periods separated by 30 seconds of nonscanning periods
- hemodynamic changes
- scanner noise to baseline levels
TD Paradigm
50 sec
press a button if they heard
only two high tones, in
preceding series
tone: 150 msec
between tones: 250 msec
Monitored both time of response and number of
correct answers
Tonotopic mapping
FT Paradigm
• Sequentially touch their fingers
to thumb
• Self-paced at the fastest
consistent pace
• Only right hand tested
Right Finger Tapping
Image Analysis
• Group Average activation map while
they performed a given task in the
presence or absence of
amphetamines
• Used to identify ROIs
• Individual activation maps
• Volume of activation
• Average % signal change in a ROI
Results
• Amphetamines increased hr,
sBP, dBP
• Amphetamine-like effects:
euphoria, feeling of a drug high,
liking the drug, wanting more
drug
Measure of performance on
TD task during fMRI scan
No effect on performance
TD Task
FT Task
Why the increase in
activated voxels?
• Amphetamine may have
increased number of neurons
recruited to do the task
• Same neurons normally
activated by the task may have
been activated to a greater
extent with amphetamine
• Direct vascular effects
Conclusions
• 20mg d-amphetamine produced
significant region-specific
changes without changes in
performance in right-handed
males
Confounds
• Contrary to previous studies,
amphetamine induced region
specific changes in activation during
the FT task
• Current study found greater sensoryinduced activation than previous
studies
• Administration methods:
- lower dosage (5mg) (Howard et al.,1996)
- intravenous cocaine (Gollub et al., 1998)
Limitations
• Affective and cognitive effects
of amphetamine mediated by DA
• Here, amphetamine increased
activation in areas that don’t
receive major DA projections
Future Outlook
• Investigate how the effects of
amphetamine on DA function
interact with the effects of
amphetamine on behaviors not
normally associated with DA
• How the effects of DA on mood and
affect interact with its effects on
cognition and motor performance