2013

http://informahealthcare.com/adaISSN: 0095-2990 (print), 1097-9891 (electronic)

Am J Drug Alcohol Abuse, 2013; 39(6): 341–342! 2013 Informa Healthcare USA, Inc. DOI: 10.3109/00952990.2013.856661

INTRODUCTION

An introduction to ‘‘The addiction connectome: brain connectivity indrug and alcohol addiction’’

One of the most exciting advances in our understanding of

brain functioning over the past two decades is the mapping

of the human brain ‘‘connectome,’’ or the brain’s integrated

neural circuitry, through which we have learned about

the brain’s connectivity. Brain connectivity can be evaluated

in terms of integrity of white matter fiber tracts (structural) or

temporal correlation of neural signals across brain regions

(functional). In addiction research, atypical brain connectivity

has been observed in various substance abusing groups (e.g.,

alcohol, cocaine, marijuana) across the lifespan (i.e., adoles-

cents, adults) as well as in those considered sub-clinical or at-

risk. This special issue highlights advancements in our

knowledge of the ‘‘addiction connectome’’ (i.e., the neural

structural and functional wiring in the addicted brain) and its

role in the development and maintenance of addiction. These

invited papers demonstrate the multiple dimensions by which

addiction research has informed current knowledge through

various approaches in brain connectivity (e.g., independent

component analysis [ICA]; psychophysiological interaction

[PPI]; diffusion tensor imaging [DTI]).

This introduction offers a brief overview of the wide range

of studies presented in this special issue. Specifically, this

body of work sheds light on the vulnerability to addiction

(e.g., potential neural risk markers that predate the onset of

the clinical presentations of addiction), the biologic under-

pinnings of addiction (e.g., provides an improved under-

standing of the fundamental neurobiological circuitry that

underlies the complex symptoms of addiction, such as

impulsivity, reward/motivation), and treatment approaches

to addiction (e.g., how might our knowledge of the addiction

connectome facilitate the improvement of treatment strate-

gies?). The specific contributions of the individual articles are

described.

1. Vulnerability to addiction

Potential markers in neural connectivity that reflect vulner-

ability to addiction are described by Luciana et al. (pages 345

to 355). In a two-year prospective study, the authors teased

apart structural connectivity patterns that distinguish adoles-

cents who transitioned into regular alcohol use from those

who did not. Neural distinctions revolved around the blunted

development of white matter in several areas coupled with

decreased white matter integrity, as measured by diffusion

tensor imaging (DTI) and fractional anisotropy (FA), despite

the lack of difference in premorbid characteristics. This

deviation from typical neurodevelopment suggests a possible

neurodevelopmental lag in those who are at-risk for alcohol

use disorders (AUD).

Spadoni et al. (pages 356 to 364) tested this ‘‘neuroma-

turational lag’’ hypothesis directly by comparing adolescents

with a family history of alcohol use disorders from those

without a family history and also in older adolescents. They

report that during a spatial working memory task, functional

connectivity differed in those with familial risk compared to

both young adolescents without a family history of AUD and

in older adolescents. These findings propose that less mature

connectivity can identify adolescents at risk for drinking

problems.

2. The biologic underpinnings of addiction

Thayer et al.’s (pages 365 to 371) study provides evidence that

decreased white matter integrity via lower DTI FA is also

evident following the onset of problematic drinking. The

authors compared juvenile justice–involved adolescents with

high scores on the Alcohol Use Disorders Identification Test

(AUDIT) with juvenile justice–involved adolescents with low

AUDIT scores and found lower FA values in projection fibers

of the basal ganglia. Exploratory analyses further showed an

inverse relationship between FA and impulsivity scores. This

demonstrates potential neurotoxic effects of heavy alcohol use

on white matter microstructure that is associated with risk-

taking in adolescents.

Orr et al. (pages 372 to 381) evaluated how intrinsic

connectivity networks differed between marijuana dependent

and non-dependent adolescents. The authors report increased

spontaneous signal fluctuations (amplitude of the low

frequency fluctuations [ALFF]) underlying resting-state

functional connectivity (rsFC) in right hemispheric regions

in dependent adolescents. They further noted stronger intra-

hemispheric functional connectivity in the marijuana depen-

dent adolescents versus controls.

Am

J D

rug

Alc

ohol

Abu

se D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

10/2

5/14

For

pers

onal

use

onl

y.

These differential connectivity patterns based on severity of

use are consistent with those observed in marijuana-using

adults. Filbey and Yezhuvath (pages 382 to 391) explored

inhibitory control networks in dependent versus non-depen-

dent adult users. While network activation did not differ

between the two severity groups, greater network connectivity

was found in dependent compared to non-dependent users.

The report by Mitchell et al. (pages 392 to 402) further

supports the possibility of either a compensatory mechanism

or a failure of inhibitory networks to regulate in addiction.

Specifically, the authors examined task-dependent connectiv-

ity using the Stroop Task, a classic task of response inhibition,

in cocaine users. Compared to non-users, cocaine users

showed greater connectivity in inhibitory and reward net-

works, suggesting greater motivational processes in cocaine

users.

Focusing on the role of the insular connectivity during

impulsivity, Wisner et al. (pages 403 to 413) report on weaker

inter-network connectivity between intrinsic connectivity

networks (ICNs) in frontal areas as well as an ICN in the

striatum in cocaine users relative to controls. This pattern was

inversely related to impulsivity in cocaine users, elaborating

on the interaction between frontal control and reward areas as

they relate to impulsivity.

3. Treatment approaches to addiction

In high-risk adolescents from the juvenile justice system,

Houck et al. (pages 414 to 423) investigated how intrinsic

resting state connectivity networks may be related to mari-

juana use. They found that during rest, an area within the

frontal control network positively correlated with marijuana

use. This investigation of high-risk adolescents that are

intermediary between community and treatment samples

provides a unique opportunity for directly linking risk with

implications for treatment.

Trait impulsivity (versus state) is also thought to be due to

dysregulation in frontal cortical function coupled with striatal

function. McHugh et al. (pages 424 to 432) investigated this

notion in cocaine-addicted individuals during resting state.

Reductions in cortico-striatal circuit connectivity was found

to be mediated by impulsivity scores and, importantly,

primarily driven by cocaine-addicted individuals who subse-

quently relapsed. This work discusses the role of connectivity

in determining risk for relapse and poses a potential target for

more effective treatment strategies.

Orban et al. (pages 433 to 440) examined how resting state

networks related to state anxiety may also be related to

symptoms of alcohol use. They found reductions in connect-

ivity in anxiety-related networks in alcohol-dependent

patients. This provides evidence for varying neural correlates

of state anxiety between alcohol dependent patients who do

not have anxiety disorders and patients with clinical anxiety

disorders. These findings have implications for those with

comorbid addictions and affective disorders.

In conclusion, our rapidly growing understanding of the

addiction connectome has given us new avenues to probe the

integrated brain systems that underlie addiction. Future work

can expand on this knowledge by determining individual

differences, such as genetic and environmental factors, that

influence the addiction connectome.

Thank you to all of the authors who contributed their

important work to this special issue.

Francesca M. Filbey, PhD

Center for BrainHealth

School of Behavioral and Brain Sciences

The University of Texas at Dallas

TX 75235, USA

E-mail: Francesca.Filbey@utdallas.edu

342 F. M. Filbey Am J Drug Alcohol Abuse, 2013; 39(6): 341–342

Am

J D

rug

Alc

ohol

Abu

se D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

10/2

5/14

For

pers

onal

use

onl

y.