Imaging the Addicted Brain

242 Pages·2016·6.82 MB·English

by  Natalie M. Zahr and Eric T. Peterson (Eds.)

INTERNATIONAL
REVIEW OF
NEUROBIOLOGY
VOLUME129
SERIES EDITORS
R. ADRON HARRIS
WaggonerCenterforAlcohol andDrugAddictionResearch
The University of Texas at Austin
Austin, Texas, USA
PETER JENNER
Division of Pharmacology and Therapeutics
GKT School of Biomedical Sciences
King's College, London, UK
EDITORIAL BOARD
ERICAAMODT HUDAAKIL
PHILIPPEASCHER MATTHEWJ.DURING
DONARDS.DWYER DAVIDFINK
MARTINGIURFA BARRYHALLIWELL
PAULGREENGARD JONKAAS
NOBUHATTORI LEAHKRUBITZER
DARCYKELLEY KEVINMCNAUGHT
BEAULOTTO JOSE(cid:1)A.OBESO
MICAELAMORELLI CATHYJ.PRICE
JUDITHPRATT SOLOMONH.SNYDER
EVANSNYDER STEPHENG.WAXMAN
JOHNWADDINGTON
AcademicPressisanimprintofElsevier
50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates
525BStreet,Suite1800,SanDiego,CA92101-4495,UnitedStates
TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom
125LondonWall,London,EC2Y5AS,UnitedKingdom
Firstedition2016
Copyright©2016ElsevierInc.Allrightsreserved.
Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,
electronicormechanical,includingphotocopying,recording,oranyinformationstorageand
retrievalsystem,withoutpermissioninwritingfromthepublisher.Detailsonhowtoseek
permission,furtherinformationaboutthePublisher’spermissionspoliciesandour
arrangementswithorganizationssuchastheCopyrightClearanceCenterandtheCopyright
LicensingAgency,canbefoundatourwebsite:www.elsevier.com/permissions.
Thisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightby
thePublisher(otherthanasmaybenotedherein).
Notices
Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchand
experiencebroadenourunderstanding,changesinresearchmethods,professionalpractices,
ormedicaltreatmentmaybecomenecessary.
Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgein
evaluatingandusinganyinformation,methods,compounds,orexperimentsdescribed
herein.Inusingsuchinformationormethodstheyshouldbemindfuloftheirownsafetyand
thesafetyofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility.
Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,
assumeanyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterof
productsliability,negligenceorotherwise,orfromanyuseoroperationofanymethods,
products,instructions,orideascontainedinthematerialherein.
ISBN:978-0-12-803914-4
ISSN:0074-7742
ForinformationonallAcademicPresspublications
visitourwebsiteathttps://www.elsevier.com/
Publisher:ZoeKruze
AcquisitionEditor:KirstenShankland
EditorialProjectManager:HannahColford
ProductionProjectManager:SuryaNarayananJayachandran
CoverDesigner:MathewLimbert
TypesetbySPiGlobal,India
CONTRIBUTORS
I.M.Balodis
YaleUniversity,NewHaven,CT,UnitedStates
T.Brumback
UniversityofCalifornia,SanDiego,LaJolla;VASanDiegoHealthcareSystem,SanDiego,
CA,UnitedStates
N.Castro
UniversityofCalifornia,SanDiego,LaJolla,CA,UnitedStates
S.Chanraud
EPHE,PSLResearchUniversity,Bordeaux,France
D.B.deAraujo
BrainInstitute/HospitalUniversitarioOnofreLopes,UFRN,Natal,Brazil
L.T.Dowdle
MedicalUniversityofSouthCarolina,Charleston,SC,UnitedStates
M.Dupuy
EA4136-HandicapetSyste`meNerveux,BordeauxUniversity;INCIA—Bordeaux
University,UMR5287CNRS,Bordeaux,France
J.Gallinat
UniversityClinicHamburg-Eppendorf,ClinicandPolyclinicforPsychiatryand
Psychotherapy,Hamburg,Germany
C.A.Hanlon
MedicalUniversityofSouthCarolina,Charleston,SC,UnitedStates
J.Y.Hong
SRIInternational,MenloPark,CA,UnitedStates
J.Jacobus
UniversityofCalifornia,SanDiego,LaJolla;VASanDiegoHealthcareSystem,SanDiego,
CA,UnitedStates
J.L.Jones
MedicalUniversityofSouthCarolina,Charleston,SC,UnitedStates
E.Kalon
PaloAltoUniversity,PaloAlto;SRIInternational,MenloPark,CA,UnitedStates
S.Ku€hn
UniversityClinicHamburg-Eppendorf,ClinicandPolyclinicforPsychiatryand
Psychotherapy,Hamburg;CenterforLifespanPsychology,MaxPlanckInstituteforHuman
Development,Berlin,Germany
M.N.Potenza
YaleUniversity,NewHaven,CT,UnitedStates
vii
viii Contributors
T.Schulte
PaloAltoUniversity,PaloAlto;SRIInternational,MenloPark,CA,UnitedStates
S.Tapert
UniversityofCalifornia,SanDiego,LaJolla,CA,UnitedStates
L.F.To´foli
SchoolofMedicalSciences,UniversityofCampinas,Campinas,Brazil
C.Tobin
PaloAltoUniversity,PaloAlto;NationalCenterforPTSD,VAPaloAltoHealthCare
SystemMenloParkDivision,MenloPark,CA,UnitedStates
PREFACE
InconsideringtopicsforthisissueoftheInternationalReviewonNeurobiology,
weincludedworkevaluatingdrugsofabuse,namelyalcohol,stimulants(such
ascocaine),andmarijuana,andcompulsivebehaviors,notablysex,food,and
gambling.Addictiontonearlyallsubstancesisdiagnosedbasedoncommon
criteria(Table1),whichcanreadilybeappliedtobehavioraladdictions.
In addition to classifying Substance Use Disorders, the Diagnostic and
Statistical Manual of Mental Disorders (DSM-5) now includes gambling as
an independent condition in a new category on behavioral addictions.
The American Psychiatric Association chose not to include sex addiction as
adistinctdiagnosticcategory,notingthat,aswith“foodaddiction,”theserel-
ativelynewconceptsrequirefurtherinvestigationbeforeinclusionasdistinct
diagnosticcategories.Behavioral,or“chemical-free,”addictionsnevertheless
offerausefulviewoftheaddictedbrainindependentofthepresenceofadrug.
Thisvolumepresentsdiverseanduniqueperspectivesonaddictionfrom
the viewpoint of neuroimaging.
Maud Dupuy and Sandra Chanraud review neuroimaging of Alcohol
Use Disorders with an emphasis on disrupted brain connectivity and com-
pensatory mechanisms, often mediated by the cerebellum, as reported in
studies using Diffusion Tensor Imaging (DTI) and resting-state functional
magnetic resonance imaging (rsfMRI).
Ty Brumback, Norma Castro, Joanna Jacobus,and Susan Tapert review
neuroimagingofmarijuanausewithafocusonadolescence.Theynotethat
thiscriticalneurodevelopmentalperiodisespeciallyvulnerabletoexposureto
drugsofabuse,whichcansignificantlyalterthetrajectoryofbrainmaturation.
SimoneKu€hnandJu€rgenGallinatreviewtheneurobiologicalbasisofsex
addiction,maintainingthatuseofanunbiasedtermsuchas“hypersexuality”
will help advance our understanding of the brains of individuals with per-
sistent, socially deviant, maladaptive sexual behavior.
Ember Kalon, Jui-Yang Hong, Chelsea Tobin, and Tilman Schulte
establish a theoretical framework from which to evaluate food addiction,
review fMRI studies of obesity and food-cue reactivity, and highlight the
relevance of the hypothalamus to brain homeostasis.
IrisBalodisandMarcPotenzareviewbrainresponsestocueandreward
processing fMRI tasks to derive mechanisms of cognitive compromise in
gambling disorder.
ix
x Preface
Table1 DSM-VCriteriaforDiagnosingSubstanceUseDisorders
1.Substanceisoftentakeninlargeramountsoveralongerperiodoftimethanwas
intended
2. Persistentdesire or unsuccessful effort to cut down or controluse
3. Excessive time spent inactivitiesnecessaryto obtain,use, or recover from
substance
4. Cravingor astrong desire to usethe substance
5. Recurrent use resultinginfailure tofulfill major obligationsat work,school,
home
6. Continueduse despite having persistentor recurrentsocial or interpersonal
problems
7.Importantsocial,occupational,orrecreationalactivitiesaregivenuporreduced
because of substance use
8. Tolerance, as defined byeither of the following:
a.A need formarkedly increased amounts of the substance to achieve
intoxication or desired effect
b.A markedly diminishedeffectwith continued useof the same amountof
substance
9. Withdrawal, as manifestedby either of the following:
a.Characteristic withdrawal syndrome for the substance
b.Use of the substance or closely related substance is taken to relieve or avoid
withdrawal symptoms
Colleen Hanlon, Logan Dowdle, and Jennifer Jones, in addition to
reviewing imaging studies of the brain on cocaine, consider current studies
evaluatingtheuseoftranscranialmagneticstimulation(TMS)totreataddiction.
Lu´ıs Fernando To´foli and Draulio Barros de Araujo review electroen-
cephalogram studies of psychedelics conducted in the early 1960s, report
on the current “psychedelic renaissance,” and underscore the potential of
psychedelicstobeusedinacontrolledtherapeuticsettingtotreataddiction.
What emerges from these contributions is that neuroimaging, which
permitsinvivo,whole-brainanalysisofthehumancondition,hasrevealed
that brains of individuals with an addiction diagnosis, irrespective of sub-
stanceorbehavior,showalterationsinoverlappingbrainsystems,including
reward, stress, and executive control networks.
Therelationbetweendrugsofabuseandthebrain’srewardcircuitry,first
explored in the 1950s, has remained a central focus of addiction research.
Preface xi
Thetermrewardsystemreferstoagroupofstructuresthatrespondtoreward-
ingorreinforcingstimuli.Whenexposedtoarelevantstimulus(eg,drugsof
abuse), thebrainresponds by increasingtherelease of theneurotransmitter
dopamine,whichisassociatedwiththeexperienceofa“high”orfeelingsof
euphoria.Themesolimbicdopaminesystemincludesdopamine-producing
structures (eg, ventral tegmental area) and dopamine-responsive structures
(eg, ventral striatum/nucleus accumbens). A consistent finding in the
addictedbrainisthatcontinueduseorexposurereducesdopaminereceptor
expression in areas such as the nucleus accumbens, thereby reducing the
rewardresponsetothesubstanceorbehavior,amechanismthatmayunder-
lie the expression of tolerance. As use progresses to abuse, the rewarding
properties of the drug become less salient and drug taking becomes guided
instead by conditionedresponses(ie, habit) likelymediated by moredorsal
aspects of the striatum.
Aconsiderablebodyofworknowsupportstheconceptoftheaddicted
brainashavingastresssurfeit,oftenduringwithdrawal,andgenerallyasso-
ciated with dysregulation of the brain’s limbic system. In the transition to
addiction, motivation shifts from desire to experience the positive effects
of the drug or behavior to avoidance of the negative effects, such as those
that accompany withdrawal. The brain in withdrawal, associated with irri-
tability,physicalandemotionalpain,dysphoria,andalossofmotivationfor
natural rewards, responds to stress-related chemicals such glucocorticoids,
corticotropin-releasing factor (CRF), norepinephrine, and dynorphin.
CRF- and dynorphin-producing neurons are present in a number of brain
regions: neuroimaging research has principally focused on the amygdala,
which appears to be hyperactive in the addicted brain.
Theaddictedbrainalsoshowsdeficitsinthefunctioningoftheexecutive
control system, governing cognitive functions including decision-making,
workingmemory,outcomeexpectation,andplanning.Thefrontallybased,
executivecontrolsystemtargetsmanycortical,subcortical,anddiffuseneu-
rotransmittersystems,includingdopaminergic,noradrenergic,serotoniner-
gic, and cholinergic neurons in the basal forebrain and brainstem.
Engagement of frontal executive systems early in the addiction process in
response to irregular activity in the brain’s reward and stress systems may
contribute to the transition from casual to compulsive behavior. Later in
addiction, compromise of the executive system, including prefrontal,
orbitofrontal, and anterior cingulate cortices, may result in loss of control,
failure of self-regulation, poor decision-making, and impulsivity.
ThisspecialissueoftheInternationalReviewofNeurobiologyconcludeswith
chapters focused on treating addiction. While still in its infancy, research
xii Preface
examiningthebrain’sresponsetoTMSandpsychedelictherapyholdspromise
for assisting individuals in overcoming addiction. An FDA-approved treat-
mentformajordepressivedisordersince2008,TMSiscurrentlybeingeval-
uated as a treatment for a number of substance use disorders. TMS targets
to reduce craving include the nucleus accumbens and prefrontal cortex.
Psychedelics may be beneficial in a comprehensive treatment setting as they
are serotonin receptor agonists: a number of addictive behaviors, including
hypersexuality, appear to respond to selective serotonin reuptake inhibitors,
which,likepsychedelics,effectivelyincreaseserotonergicactivityinthebrain.
Fromourperspectiveaseditorsofthisissue,otherbrainregionsrelevantto
theaddictedbrainrequireadditionalinvestigation.Inparticular,thecerebel-
lum,whichappearstocompensateforfunctionalimpairmentsinalcoholuse
disorders, has not been systemically investigated in neuroimaging studies of
nonalcohol substance use disorders or in behavioral addictions. Similarly,
althoughrelevanttoregulatinganumberofaddictive-likebehaviorsandger-
manetorodentstudiesofaddiction,thehypothalamus,likelyduetoitssmall
size and location, is relatively understudied with current neuroimaging
methods.Furtherinvestigationofthedevelopingadolescentbrainisalsonec-
essaryasitisanticipatedthatsuchstudieswillhelpdistinguishabrainatriskfor
froma brain already hijacked by addiction. Individual differences in vulner-
ability to drugs and the transition to addiction also require further scrutiny.
Finally,wewouldliketothankeachoftheauthorswhohavecontributed
timely and thoughtful reviews on “Imaging the Addicted Brain.” It was a
pleasure to serve as editors for this volume of the International Review of
Neurobiologyandwepredictthatresearchersandcliniciansalikewillfindthis
resourceacomprehensiveguidetoabiologicallybasedunderstandingofthe
addicted brain.
Conflictofinterest:Theauthorsdeclarenocompetingfinancialinter-
est in relation to the work described here.
NATALIE M. ZAHR
Neuroscience Program,
SRI International,
Menlo Park, CA, United States
Psychiatry & Behavioral Sciences,
Stanford University School of Medicine,
Stanford, CA, United States
ERIC T. PETERSON
Neuroscience Program,
SRI International,
Menlo Park, CA, United States
CHAPTER ONE
Imaging the Addicted Brain:
Alcohol
M. Dupuy*,†,1, S. Chanraud{
*EA4136-HandicapetSyste`meNerveux,BordeauxUniversity,Bordeaux,France
†INCIA—BordeauxUniversity,UMR5287CNRS,Bordeaux,France
{EPHE,PSLResearchUniversity,Bordeaux,France
1Correspondingauthor:e-mailaddress:[email protected]
Contents
1. AlcoholUseDisorder:Definition,Epidemiology,andConsequences 2
1.1 Definitions 2
1.2 Epidemiology 2
1.3 Consequences 3
1.4 ImagingtheBrain 3
2. StructuralBrainImaginginAUD 4
2.1 MacrostructuralBrainImaginginAUD 4
2.2 MicrostructuralBrainImaginginAUD 9
3. FunctionalBrainImaginginAUD 11
3.1 Activation 11
3.2 FunctionalConnectivity 15
4. Conclusion 24
References 24
Abstract
Alcoholusedisorder(AUD)representsamajorpublichealthissueduetoitsprevalence
and severe health consequences. It may affect several aspects of an individual's life
includingworkandrelationships,anditalsoincreasesriskforadditionalproblemssuch
asbraininjury.ThecausesandoutcomesofAUDarevaried;thus,attemptingtounder-
stand this complex phenomenon requires investigation from multiple perspectives.
Magneticresonanceimaging(MRI)isapowerfulmeanstoinvestigatebrainanatomical
andfunctionalalterationsrelatedtoAUD.RecentadvancesinMRImethodsallowbetter
investigationofthealterationstostructuralandfunctionalbrainnetworksinAUD.Here,
wefocusonfindingsfromstudiesusingmultipleMRItechniques,whichconvergeto
supporttheconsiderablevulnerabilityoffrontalsystems.Indeed,MRIstudiesprovide
evidencefora“disconnectionsyndrome”whichcouldbeinvolvedinthepoorbehav-
ioralcontrolobservedinAUD.
InternationalReviewofNeurobiology,Volume129 #2016ElsevierInc. 1
ISSN0074-7742 Allrightsreserved.
http://dx.doi.org/10.1016/bs.irn.2016.04.003
2 M.DupuyandS.Chanraud
1. ALCOHOL USE DISORDER: DEFINITION,
EPIDEMIOLOGY, AND CONSEQUENCES
1.1 Definitions
Alcohol is a psychoactive substance with dependence-producing properties.
In most cultures, it is the most frequently used intoxicating substance. The
definition of alcohol use disorder (AUD) has varied over the years. In the
fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (4th
ed., text revision; DSM-IV-TR; American Psychiatric Association, 2000),
the diagnoses included categories of “alcohol abuse” and “alcohol
dependence,” each with specific criteria. The fifth edition, DSM-5 (5th
ed., DSM-5; American Psychiatric Association, 2013), combines the two
DSM-IV categories of “alcohol abuse” and “alcohol dependence” into one
disorder called AUD, measured on a continuum from mild to severe,
accordingtonumberofcriteriamet.IntheDSM-5,recurrentlegalproblems
asa criterion foralcoholabuse was removed,asitwasa difficult criterion to
apply internationally, considering differences in legal practices; a new
criterion—cravingorastrongdesiretousealcohol—wasadded.Itwasnoted
thatthediagnostictermof“dependence”isconfusing.Indeed,“dependence”
and “addiction” are two terms that are often used interchangeably, even
though they refer to different phenomena. According to the American
Psychiatric Association (2013) “dependence can be a normal body response
to a substance.” The term “addiction” is not considered in the Diagnostic
and Statistical Manuals of Mental Disorders as it has an uncertain definition
and is potentially associated with a negative connotation.
Regardless of the exact definition used, substance-related disorders are
complexphenomenathathavevariousinterpretationsintheliterature.They
haveanarrayofcausesandconsequencesthatmaycooccurwithotherchronic
diseasesandaffectvariousfacetsofanindividual’slife,family,andcommunity,
aswellassocietyasawhole.Theunderstandingofthesephenomenaconsti-
tutesabroadfieldofstudythatspansseveraldisciplinesandapproaches.The
scientific findings reported in this chapter mainly deal with alcohol depen-
dence, as defined by DSM-IV-TR, and with AUD, as it is described in the
DSM-5, and additionally relate results concerning abstinence and relapse.
1.2 Epidemiology
Estimating the prevalence of AUD is difficult considering differences in
researchmethodologyandchangesinthediagnosticcriteriaovertheyears.
In 2010 however, the worldwide prevalence of AUD among individuals