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

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

What is Craving ?What is Craving ?State evoked by People, Places and Things

associated with drug use

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

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

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

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

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

What Does Craving Do ?What Does Craving Do ?

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

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

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.

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

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

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

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 ?

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

CORTICAL ACTIVATION DURINGGAMBLING TASK

R

R

p<0.001, Extent = 10 pixels, uncorrected (11 Abusers + 11 Controls)

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)

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)

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

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)

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)

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)

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)

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

What Does Craving Do ?What Does Craving Do ?Dysregulation of Cognition

• Evokes Memory • Captures Attention• Biases Decision-Making