methamphetamine and the brain: a problem of inhibitory control edythe d. london, ph.d. david geffen...
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![Page 1: Methamphetamine and the Brain: A Problem of Inhibitory Control Edythe D. London, Ph.D. David Geffen School of Medicine, UCLA](https://reader035.vdocuments.mx/reader035/viewer/2022062714/56649d265503460f949fdbe0/html5/thumbnails/1.jpg)
Methamphetamine and the Brain: A Problem of Inhibitory Control
Edythe D. London, Ph.D.David Geffen School of Medicine, UCLA
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Cognitive Deficits decision-making
response inhibition
Inhibitory Control Problems (Impulsivity)
Mood Disorder anxiety
depression
Inhibitory Control Problems
Drug AbuseDrug Abuse
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HIV Prevalence in LA County heroin injectors at low risk
gay male METH users at extreme risk
LAC HIV Epidemiology (1999-2004);Methamphetamine Use Among Gay and Bisexual Men in LA.
http://www.uclaisap.org/documents/final-report_cjr_1-15-04.pdf.
7
10
61
0
0 20 40 60 80
Street heroin addicts
Heroin addicts Methadone clinics
Outpatient clinic, gay/bi
Outpatient clinic, heteroMETH-dependent subjects
% HIV Positive
METH-dependent subjects
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Brain Metabolism During Early Abstinence from Methamphetamine
t-values
2.5
1.5
3.5
0.5
Control > MA
Amygdala
Medial PFC
MA >Control
5
3
1
2
4
ED London et al., Arch. Gen. Psychiatry, 2004
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Mood Disorder in METH Abuse:Related to Glucose Metabolism
ED London et al., Arch. Gen. Psychiatry, 2004
2
4
6
(+)
t-values
5
3
1
2
4
(-)
Depression Anxiety Depression Anxiety
Amygdala
PFC
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Loss of Cortical Inhibition of the Amygdala
2.5
1.5
3.5
0.5Contro
l> MA
t-values
MA >Control
5
3
12
4
Environmental stimuli exaggerated responses
● depression ● anxiety ● craving ●hostility
OFC Amygdala
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Gray Matter Deficits in Cortex
PM Thompson et al., J. Neurosci., 2004
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Gray Matter Deficit inPrefrontal Cortex
PM Thompson et al., J. Neurosci. 2004
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Impairment on the Stop-Signal Taskis Related to Methamphetamine Use
J. Monterosso et al., Drug Alcohol Depend., 2005
controlnonsmoker
controlsmoker
METHusers
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Conscious Emotion Control during fMRI
K. Baicy et al., Abstr. Soc. Neurosci, 2006K. Baicy et al., Abstr. Soc. Neurosci, 2006
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METH-Dependent Subjects have LowerEmotion Ratings than Healthy Subjects
MAMAControlControl MAMAControlControl
* * p = 0.02 vs. “Look”p = 0.02 vs. “Look”
**p = 0.02p = 0.02vs. controlvs. control **p = 0.02p = 0.02
vs. controlvs. control
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Greater Response of Amygdala inMETH-Dependent Subjects
METH-dependent subjects > controlLOOK negative > neutral
left amygdala, p<0.001 uncorrected, t = 5.68
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Greater Activation of PFC in Healthy Subjects During Cognitive Reappraisal
Control > METH dependent subjectsDECREASE > LOOK
p = 0.026, corrected false discovery rate (FDR), t = 4.16
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Affect Matching Task
Which of the two bottom pictures matches the emotion shown on top?
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METH Dependence
T
P<.005, 10 voxel extent(n = 12/group)
D Payer et al., manuscript in review 2007
Dorsal ACC activityDorsal ACC activity
correlated withcorrelated with::• hostilityhostility
• interpersonal sensitivityinterpersonal sensitivity
Pain, Socioemotional threat Emotion integration, InhibitionT
Heightened Activation: Dorsal ACC
Blunted Activation:Right Ventrolateral PFC
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PFC/ ACC Activation (Cons)
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
-2 -1 0 1 2 3 4 5
RVLPFC
dA
CC CON
MA
Negative Correlation of Activityin Right VLPFC and dACC
Problems inhibiting threat response in METH dependence?.....
r = -.516, p < .001
Po
ste
rior
AC
CP
ost
erio
r A
CC
Right Ventrolateral PFCRight Ventrolateral PFC
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Therapy for Impairments
InhibitoryControl
BehavioralTherapy
PharmacologicalTherapy
Medications used for Other disorders:
ModafinilBupropion
Cognitive Behavioral Therapy Attention Process Training
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Acknowledgements
Walter LingRichard RawsonTom NewtonSara SimonTimothy Fong
Steve BermanJohn MonterossoPaul ThompsonRussell PoldrackRoger Woods
UCLA Faculty
Grant support: R01 DA 15179 (EDL), R01DA020726 (EDL), Contract 1YO1 DA 50038 (WL, EDL)
K01 DA00515-01A1 (JM), MOI RR 00865
Jennifer LearnYun DongAaron Lichtman
Research Fellows Students
Kate BaicyDoris Payer