cognitive neuroscience of cravingdrug abusers show abnormal brain activity in . ventral prefrontal...
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Cognitive Neuroscience of CravingCognitive Neuroscience of Craving
Steven Grant, Ph.D. Steven Grant, Ph.D. Clinical Neurobiology BranchClinical Neurobiology Branch
Division of Treatment Research & Division of Treatment Research & DevelopmentDevelopment
National Institute on Drug AbuseNational Institute on Drug Abuse
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Cognitive Neuroscience of CravingCognitive Neuroscience of CravingCo-Investigators
Katherine Katherine BonsonBonson, Ph.D. , Ph.D. Carlo Carlo ContoreggiContoreggi, M.D., M.D.EdytheEdythe London, Ph.D. London, Ph.D.
Monique Ernst, M.D., Ph.D.Monique Ernst, M.D., Ph.D.
Staff of NIDA-IRP Brain Imaging CenterJennifer Bragg, Jennifer Bragg, Varughese KurianVarughese Kurian, M.S., CNMT, Mark Waller, CNMT, M.S., CNMT, Mark Waller, CNMT
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What is Craving ?What is Craving ?State evoked by People, Places and Things
associated with drug use
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Time Course of CravingTime Course of Craving
Average CravingWithin Session
0
2
4
6
8
10
NeutralCues CocaineCuesC
ravi
ng
Time Course of CravingDuring Session
0
2468
10
Pre 10 20 30minutes
Cra
ving
Neutral CuesCocaine Cues
Bonson, et al Neuropsychopharmaocology, 2002
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HIGH CRAVER LOW CRAVER
AM
DL
PH
00
22
44
66
88
NeutralNeutralCuesCues
CocaineCocaineCuesCues
Cra
ving
Sco
rC
ravi
ng S
cor 10e 10e
NeutralNeutral CocaineCocaine
r = 0.66p < 0.02
00112233445566
--11 --0.50.5 00 0.50.5 11 1.51.5
�� rCMRglcrCMRglc
��C
ravi
ngC
ravi
ng
Medial TemporalMedial Temporal
00112233445566
--11 --0.50.5 00 0.50.5 11 1.51.5 22
�� rCMRglcrCMRglc
��C
ravi
ngC
ravi
ngDorsolateral PrefrontalDorsolateral Prefrontal
00112233445566
--11 --0.50.5 00 0.50.5 11 1.51.5 22
�� rCMRglcrCMRglc
��C
ravi
ngC
ravi
ng
r = 0.66p < 0.02
r = 0.66p < 0.02
NeutralNeutral CocaineCocaine
CerebellumCerebellum
22
Grant et al. PNAS, 1996
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Activations and Deactivations During Activations and Deactivations During Presentation of Cocaine CuesPresentation of Cocaine Cues
DeactivationDeactivationActivationActivation
Bonson, et al Neuropsychopharmaocology,
2002
p<0.005, uncorrected. Extent = 10 pixels. N = 11
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Overlap of Activations and Overlap of Activations and Correlations with CravingCorrelations with Craving
ActivationActivation
Correlation Correlation (r > 0.7)(r > 0.7)
Bonson, et al Neuropsychopharmaocology,
2002
p<0.005, uncorrected. Extent = 10 pixels. N = 11
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Positive Correlation with CravingPositive Correlation with Cravingin Left Amygdala/in Left Amygdala/PerirhinalPerirhinal CortexCortex
Bonson, et al Neuropsychopharmaocology,
2002p<0.005, uncorrected. Extent = 10 pixels. N = 11
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What Does Craving Do ?What Does Craving Do ?
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Craving Captures AttentionCues + Continuous Performance Task N= 12 Cocaine Abusers N= 10 Controls
Average Session RTCocaine Abusers
500550600650700750
Pre 10 20 30
minutesm
sec
Neutral CuesCocaine Cues
Average Session RTControls
500550600650700750
Pre 10 20 30
minutes
mse
c
Neutral CuesCocaine Cues
Group X Session X Time p < 0.03
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Cocaine FilmErotic Film
IFG
Ant Cing
Cingulate
Sign
al In
tens
ity (A
U)
Cocaine Craving:Population (Cocaine Users, Controls) x Film (cocaine, erotic)
Controls Cocaine Users Garavan et al A .J. Psych 2000
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Craving Influences DecisionCraving Influences Decision--MakingMaking•• Drug Abusers show abnormal brain activity in Drug Abusers show abnormal brain activity in
Ventral Prefrontal CortexVentral Prefrontal Cortex•• Craving alters brain activity in Ventral Craving alters brain activity in Ventral
Prefrontal CortexPrefrontal Cortex•• Lesions of Ventral Prefrontal Cortex lead to Lesions of Ventral Prefrontal Cortex lead to
impaired judgment of future consequences.impaired judgment of future consequences.•• Continued drug use despite adverse Continued drug use despite adverse
consequences (DSM IV) is hallmark of consequences (DSM IV) is hallmark of addiction. addiction.
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GAMBLINGGAMBLING TASKTASK
DD
Payoff /Card
Loss /10 Cards
Profit/10 Cards
$100
$1250
-$250
$100
$1250
-$250
$ 50
$250
$250
$ 50
$250
$250
AA BB CC
NET SCORE = (C+D) NET SCORE = (C+D) -- (A+B)(A+B)
“Bad” Decks“Bad” Decks “Good” Decks“Good” Decks
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DRUG ABUSERS SHOW MARKED DRUG ABUSERS SHOW MARKED IMPAIRMENT ON GAMBLING TASKIMPAIRMENT ON GAMBLING TASK
0
10
20
30
40
Drug NaiveDrug NaiveN=24N=24
Drug AbusersDrug AbusersN = 30N = 30
p < 0.05p < 0.05 Control SubjectControl SubjectPeformancePeformance ( N = 88) ( N = 88)
from Iowafrom Iowa(A.(A. BecharaBechara, ,
Personal Personal Communication)Communication)Net Net
ScoreScore
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SUBSTANCE ABUSERS SHOW SUBSTANCE ABUSERS SHOW NO IMPAIRMENT ON WCSTNO IMPAIRMENT ON WCST
0
2
4
6
8
10
Categories CompetedCategories Competed(n.s.)(n.s.)
0
5
10
15
20
25
Perseverative ErrorsPerseverative Errors(n.s.)(n.s.)
Drug AbusersDrug AbusersN = 30
Drug NaiveDrug NaiveN=24
Drug AbusersDrug AbusersN = 30
Drug NaiveDrug NaiveN=24N = 30N=24N = 30 N=24
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IMAGING HYPOTHESESIMAGING HYPOTHESES
•• Is Is VmPFC VmPFC activated during performance of activated during performance of Gambling Task ?Gambling Task ?
•• Is Is VmPFC VmPFC activation correlated with activation correlated with performance of Gambling Taskperformance of Gambling Task
•• What other areas are activated during What other areas are activated during performance of Gambling Task ?performance of Gambling Task ?
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GAMBLING TASK PERFOMANCEGAMBLING TASK PERFOMANCE300 Cards300 Cards
-60
-40
-20
0
20
40
60
Drug Drug AbusersAbusers
WeightedWeightedNet Net
ScoreScore(50:28:22)(50:28:22)
ControlsControls
Controls > Drug Abusers p < 0.001Controls > Drug Abusers p < 0.001
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CORTICAL ACTIVATION DURINGGAMBLING TASK
R
R
p<0.001, Extent = 10 pixels, uncorrected (11 Abusers + 11 Controls)
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PET Activation vsPET Activation vsVentroMedial PreFrontalVentroMedial PreFrontal LesionsLesions
R R
BecharaBechara, et al., 1999, et al., 1999
p<0.005, Extent = 20 pixels, uncorrected (11 Abusers + 11 Contrp<0.005, Extent = 20 pixels, uncorrected (11 Abusers + 11 Controls)ols)
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SUB-CORTICAL ACTIVATION DURINGGAMBLING TASK
Extended Amygdala ?R R
R
p<0.001, Extent = 10 pixels, uncorrected (11 Abusers + 11 Contrp<0.001, Extent = 10 pixels, uncorrected (11 Abusers + 11 Controls)ols)
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Cortical Activations During Gambling Cortical Activations During Gambling Task: Controls vs. Drug AbusersTask: Controls vs. Drug Abusers
Controls (11)Controls (11)
Abusers (11)Abusers (11)
OverlapOverlap
p<0.005, uncorrected p<0.005, uncorrected Extent = 10 pixelsExtent = 10 pixels
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GROUP INTERACTION DURINGGAMBLING TASK Controls > Abusers
R
R
L
p<0.005, Extent = 10 pixels, uncorrected (11 Controls p<0.005, Extent = 10 pixels, uncorrected (11 Controls -- 11 Abusers)11 Abusers)
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GROUP INTERACTION DURING GAMBLING TASK
Abusers > Controls
p<0.005, Extent = 10 pixels, uncorrected (11 Abusers p<0.005, Extent = 10 pixels, uncorrected (11 Abusers -- 11 Controls)11 Controls)
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POSITIVE CORRELATIONS WITHGAMBLING TASK Controls r > 0.73
R
R
R
p<0.005, Extent = 20 pixels, uncorrected (11 Controls)p<0.005, Extent = 20 pixels, uncorrected (11 Controls)
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NEGATIVE CORRELATIONS WITHGAMBLING TASK Abusers r < - 0.73
R
R
L
p<0.005, Extent = 20 pixels, uncorrected (11 Controls)p<0.005, Extent = 20 pixels, uncorrected (11 Controls)
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Drug Abusers Use Different Brain Networks During Gambling Task
Controls Controls ActivationsActivations
•• L. L. InsulaInsula
Correlations (+)Correlations (+)•• R.R. InsulaInsula•• R. Superior Frontal CortexR. Superior Frontal Cortex•• R. Hippocampus/R. Hippocampus/
ParahippocampusParahippocampus•• R. Superior Parietal CortexR. Superior Parietal Cortex•• R. Inferior Temporal Cortex
AbusersAbusersActivationsActivations•• R. Superior ParietalR. Superior Parietal•• Anterior CingulateAnterior Cingulate•• R. Inf. Temporal PoleR. Inf. Temporal Pole•• Visual CortexVisual Cortex
•• Correlations (Correlations (--))•• L. Basal Forebrain/L. Basal Forebrain/
NucleusNucleus AccumbensAccumbens•• L.L. ParahippocampusParahippocampus•• L.L. Cunneus
R. Inferior Temporal CortexCunneus
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What Does Craving Do ?What Does Craving Do ?Dysregulation of Cognition
• Evokes Memory • Captures Attention• Biases Decision-Making