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) Data collection started 10 seconds after S started task Task and control periods separated by 30 seconds of non- scanning periods - hemodynamic changes - scanner noise to baseline levels

tone: 150 msec between tones: 250 msec TD Paradigm press a button if they heard only two high tones, in preceding series 50 sec 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

Contrary to previous studies, amphetamine induced region specific changes in activation during the FT task Current study found greater sensory- induced activation than previous studies Administration methods: - lower dosage (5mg) (Howard et al.,1996) - intravenous cocaine (Gollub et al., 1998) Confounds

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