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Camchong, Endres, Fein 1 Decision Making, Risky Behavior, and Alcoholism Chapter 13 - Section 5 To appear in: HANDBOOK OF CLINICAL NEUROLOGY, 3 rd Series Authors: Jazmin Camchong, PhD Michael J. Endres, PhD George Fein, PhD 3 rd Series Co-Editors: Edith V. Sullivan, Ph.D. Adolf Pfefferbaum, M.D. Series Editors: Michael Aminoff, M.D, D.Sc., FRCP Francois Boller, M.D., Ph.D. Dick Swaab Publisher: Elsevier (in press 2013)
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  • Camchong, Endres, Fein 1

    Decision Making, Risky Behavior, and Alcoholism

    Chapter 13 - Section 5

    To appear in: HANDBOOK OF CLINICAL NEUROLOGY, 3rd Series

    Authors: Jazmin Camchong, PhD Michael J. Endres, PhD George Fein, PhD 3rd Series Co-Editors: Edith V. Sullivan, Ph.D. Adolf Pfefferbaum, M.D.

    Series Editors: Michael Aminoff, M.D, D.Sc., FRCP Francois Boller, M.D., Ph.D. Dick Swaab Publisher: Elsevier (in press 2013)

  • Camchong, Endres, Fein 2

    Decision making, risky behavior and alcoholism

    A hallmark symptom of alcoholism is the continual engagement in dangerous or risky

    drinking behavior despite recurring social or personal difficulties such as alienation from friends

    and family, trouble with the law and at work, or problems with physical and emotional well-

    being. It has been suggested that the alcoholic’s propensity for such risky behavior is

    manifested by impulsive decision-making processes, wherein potential short-term appetitive

    outcomes of drinking (e.g. intoxication) are deemed more important than potential long-term

    aversive consequences of drinking (e.g., drunk driving arrests). Dual process models of

    alcoholism hold that separate but interrelated neurocognitive pathways to impulsive decision

    making exist. One reflected by weak “top-down” executive control over impulsive and

    compulsive urges to consume alcohol. The other reflected by a strong “bottom-up” appetitive

    drive in impulsive and compulsive urges to consume alcohol. The current chapter surveys

    evidence that functional and organizational patterns in brain executive control and appetitive

    drive networks characterize impulsive decision making and risky behavior in alcoholics, and

    that these patterns differ at different stages of alcoholism dependence and recovery.

    POOR EXECUTIVE CONTROL leads to poor decision making

    Impairments in executive cognitive ability have been consistently noted in alcoholics at

    various stages of alcohol dependence and recovery. Actively drinking alcoholics typically

    perform more poorly than non-substance abusing controls in a variety of neurocognitive

    domains related to attention, memory, and contingency learning (Finn and Hall, 2004, Finn et

    al., 2009, Bechara and Martin, 2004, Bogg and Finn, 2010). Finn et al. (2009) showed that

    severity of alcoholism and other related externalizing problems predicted poor short-term and

    working memory capacity, with the greatest impairments exhibited by those with other co-

    occurring externalizing behavior problems. Alcoholics’ poor cognitive capacity also has been

    linked with a broad constellation of personality traits related to impulsiveness, poor-harm

    avoidance, and antisocial behavior tendencies (Bogg and Finn, 2010). In the same vein,

    laboratory evidence has suggested that poor executive cognitive capacity is partially

    responsible for impulsive decision making in alcoholics and related externalizing syndromes

  • Camchong, Endres, Fein 3

    (Finn, 2002, Endres et al., 2011, Bogg et al., 2012). Recent evidence also shows that, when

    combined with highly impulsive trait dispositions, poor executive cognitive capacity predicts

    more heavy and dangerous drinking behavior in active alcoholics (Gunn and Finn, 2013). In

    summary, the evidence suggests that impaired or weak executive cognitive control processes

    are at least partially responsible for the impulsive decision-making tendencies and risky

    behaviors of actively drinking alcoholics.

    Alcoholics who stop drinking, and remain sober, experience recovery in some, but not

    all, domains of neuropsychological functioning. Studies have shown that while

    neuropsychological impairments in executive cognitive ability are present in recently detoxified

    and short-term abstinent alcoholics, such impairments may resolve with extended abstinence;

    nonetheless, the major recovery is observed in the first year of abstinence (Fein et al., 2006,

    Mann et al., 1999, Sullivan et al., 2000, Nixon and Glenn, 1995, Stavro et al., 2012). A recent

    meta-analysis by Stavro et al. (2012) found widespread deficits in executive cognitive ability

    characterized recently detoxified and short-term abstinent alcoholics; but, such impairments

    were dramatically attenuated in long-term abstinent alcoholics. However, Stavro et al. (2012)

    also noted a dearth of research on the persistence of inhibitory control/impulsive decision-

    making deficits in those with multi-year abstinence. A longitudinal study by Sullivan et al. (2000)

    found similar evidence of recovery, demonstrating alcoholics with sustained abstinence

    improved in short-term memory, visuospatial processing, attention, and gait and balance

    abilities. Likewise, Fein et al. (2006) showed that long-term abstinent (LTA) alcoholics with an

    average of 6.7 years abstinence did not differ from non-substance abusing controls in

    numerous executive cognitive domains, including cognitive abstraction/flexibility, attention,

    short-term/working memory, psychomotor function/reaction time, and verbal skills. For

    example, Fein et al. (2006) showed spatial processing deficits were present in LTAs. Thus,

    evidence suggests that executive cognitive impairments in attention, memory, and motor

    control to a large extent normalize with extended abstinence. However, as reviewed below,

    evidence also suggests that cognitive impairments related to the processing of appetitive

    and/or emotional information remain present in multi-year abstinent alcoholics.

  • Camchong, Endres, Fein 4

    STRONG APPETITIVE DRIVE leads to poor decision making

    Psychometric evidence has suggested that impulsive decision-making in alcoholism and related

    externalizing syndromes comprises three independent domains: myopia to the future,

    unwillingness to delay gratification, and difficulties with passive avoidance (Dom et al., 2007).

    Myopic decision-making reflects insensitivity to the long-term aversive consequences of

    appetitive goal-directed behavior and has been assessed with simulated gambling tasks such as

    the Iowa Gambling Task ) (Bechara et al., 1994). Preference for immediate gratification reflects

    a tendency to choose smaller immediate appetitive outcomes over larger delayed appetitive

    outcomes and has been assessed with intertemporal choice paradigms such as the delay

    discounting task (DDT)(Rachlin et al., 1991). Poor passive avoidance refers to difficulty stopping

    or withholding proponent or appetitive behavior so as to avoid sub-optimal or aversive

    outcomes and has been assessed with measures of inhibitory control, such as the stop-signal

    (SST)(Logan et al., 1997), go/no-go (GNG) (Newman et al., 1985), or balloon analog risk task

    (BART) (Lejuez et al., 2002).

    Acute alcohol use has disinhibiting effects on behavior control, impairing rational

    decision making and fueling such risky behavior as gambling, getting a tattoo, or having

    unprotected sex (Lin et al., 2005, Purdie et al., 2011, Tzambazis and Stough, 2000). Separate

    studies have shown active alcoholics typically make more impulsive or disinhibited decisions

    than non-substance abusing controls, with those presenting other co-occurring externalizing

    symptoms exhibiting the poorest performances on the Iowa Gambling Task, DDT, and GNG

    (Cantrell et al., 2008, Finn et al., 2002, Mazas et al., 2000, Endres et al., 2011, Bobova et al.,

    2009). Evidence also suggests that impaired processing of aversive feedback leads to impulsive

    decision-making in alcoholism and related externalizing syndromes, and this information

    processing impairment is associated with factors that predate the onset of clinical problems,

    such as a family history of alcoholism (Finn et al., 1994, Fein and Chang, 2008).

    Impulsive decision-making tendencies also have been observed in abstinent alcoholics,

    and unlike impairments in executive cognitive ability, evidence has suggested that impulsive

    decision-making tendencies persist for weeks, months, and even years of abstinence. Research

  • Camchong, Endres, Fein 5

    has shown abstinent alcoholics to be less willing to delay gratification in the DDT relative to

    non-substance abusing controls, and this effect was still present after controlling for impulsive

    personality traits (Mitchell et al., 2005). Evidence also has suggested recently detoxified

    alcoholics make more myopic decisions in the Iowa Gambling Task than controls with little to

    no improvement in this capacity at 1 month follow (Dom et al., 2007). Similar myopic decision-

    making tendencies have also been found in short-term and long-term abstinent alcoholics (Fein

    et al., 2010b), with short-term and long-term abstainers showing comparable impulsive

    decision-making during the Iowa Gambling Task relative to non-substance abusing controls

    (Ando et al., 2012). Long-term abstinent alcoholics also are known to have persistent difficulties

    with emotion perception and affective decision-making (Fein et al., 2010b, Foisy et al., 2007,

    Philippot et al., 1999, Kornreich et al., 2001, Endres and Fein, 2012). Endres and Fein (2012)

    recently showed that LTA’s persistent difficulties with passive avoidance in an affective GNG

    task were largely due to a history of externalizing problems and independent of more general

    difficulties in lexical decision-making. However, research has suggested a disassociation

    between antisocial symptoms and traits in LTA, suggesting that antisocial behaviors return to

    normal levels in the face of elevated antisocial and reward-seeking trait dispositions (Fein and

    Fein, 2012). In light of the fact that alcoholics can remain sober in spite of elevated levels of

    impulsive traits and decision-making tendencies, researchers have suggested that other

    compensatory mechanisms come into play, such as heighted executive control and

    conscientiousness aid in abstinence maintenance (Ando et al., 2012, Camchong et al., 2013a).

    When together, research has shown impulsive decision-making tendencies are present in

    alcoholics throughout the recovery process, but such impulsive personality and decision-making

    tendencies do not appear to militate against the ability to maintain abstinence.

    It is still not completely clear whether poor decision making and risky behavior

    contribute to the vulnerability of becoming an alcoholic or whether they are a consequence of

    chronic alcohol use. There is evidence supporting the idea that poor decision making exists

    before alcohol dependence. A longitudinal study on young adults in college found that poor

    decision making (as assessed with the Iowa Gambling Task) at second year of college is

    associated with heavy drinking two years later (Goudriaan et al., 2009). Poor decision making

  • Camchong, Endres, Fein 6

    (assessed with the Iowa Gambling and Stroop tasks) has also been identified in individuals at

    risk for alcoholism (with family history of alcoholism) when compared to healthy controls

    (Lovallo et al., 2006). Heavy drinking adolescents have shown poor decision making and higher

    impulsivity than light drinking adolescents (Field et al., 2007).

    There is also evidence suggesting that chronic alcohol consumption during adolescence,

    a period in which decision making brain regions are still developing, has a long-term effect on

    adult decision making. A longitudinal study using a rodent model of chronic alcohol use found

    that rats that were exposed to chronic alcohol use during adolescence had poor decision

    making (did not properly weigh benefits and costs) and preferred more risky options (chose

    large but uncertain rewards over small but certain rewards) when performing a probability-

    discounting instrumental response task in adulthood versus rats that were exposed to a

    placebo (Nasrallah et al., 2009). Further research needs to be conducted to better determine

    whether poor decision making is present before or is a consequence of alcoholism.

    Other aspects of behavior related to poor decision making in alcoholics

    Even though poor decision making has been identified in alcoholics and individuals at

    risk of becoming alcoholics, this behavioral deficit is not specific to alcoholism. Poor decision

    making in alcoholism has been associated with other aspects of behavior such as antisocial

    tendencies, stress, number of detoxifications, and onset of alcohol dependence.

    An individual with antisocial personality disorder does not adhere to accepted societal

    norms and often engages in criminal and other impulsive behavior (APA, 1994). Antisocial

    Personality Disorder is more prevalent in alcoholics than in healthy controls (Compton et al.,

    2005, Goldstein et al., 2007). Previous research has proposed that poor decision making in

    alcohol dependent individuals is increased in those with a comorbid Antisocial Personality

    Disorder. A study by Miranda et al (2009) compared risky decision making (Iowa Gambling Task

    performance) between men with alcohol dependence (abstinent >30 days) with and without

    ASPD comorbidity compared with non-substance abusing control men. Both alcoholic groups

    made significantly more risky decisions (manifested as poorer Iowa Gambling Task

    performance) than the control group. However, while alcoholics without ASPD comorbidity

  • Camchong, Endres, Fein 7

    showed a slow and steady improvement in advantageous decision making during the task,

    alcoholics with ASPD comorbidity showed an initial improvement but were unable to sustain it.

    Moreover, authors reported evidence that impulsive behavioral traits (e.g., propensity for rash

    impulsive behavior) mediated disadvantageous decision making in alcoholics with ASPD

    comorbidity. These findings suggest that poor decision making in alcoholics is closely related to

    impulsive antisocial tendencies. Because there is evidence that alcoholics’ antisocial behavior

    resolves with extended periods of abstinence, while antisocial disposition does not (Fein and

    Fein, 2012), findings of poor decision making in long-term abstinent alcoholics might be related

    to a persistent disposition to appetitive drive tendencies.

    There is evidence that decision making improves when stress is induced in actively

    heavy drinkers. A study that compared decision making in heavy and light drinkers reported

    that heavy drinkers made significantly more disadvantageous decisions than light drinkers (with

    more attention to gains and less attention to losses). When anticipatory stress was induced (by

    asking them to give a speech), decision making was improved in both heavy and light drinkers

    (by increasing attention to losses) (Gullo and Stieger, 2011). Evidence from this study suggests

    that stress is needed to better focus attention on negative consequences and hence better

    decision making. It should be noted, however, that the effect of stress on decision making may

    be different in individuals that have been diagnosed with alcohol dependence or substance

    dependence (Zhang et al., 2011). In addition, the level of stress induced by requesting

    participants to give a speech may not be severe, chronic, or realistic enough to negatively affect

    drinkers’ decision making.

    Another aspect that has been found to affect decision making in individuals with alcohol

    dependence is the number of detoxifications an individual has been through. A study that

    compared a group with fewer than 2 detoxifications (low-detox group) versus a group with >2

    detoxifications (high-detox group) reported that the low-detox group had a significantly greater

    rate of improvement in choices throughout the Iowa Gambling Task than the high-detox group

    (Loeber et al., 2009). This evidence suggests that individuals with repeated withdrawal

    episodes lack the ability to make proper decisions and to adapt behavior to newly learned rules.

  • Camchong, Endres, Fein 8

    More research needs to be conducted to find out whether poor decision making leads to

    repeated relapse episodes or whether the negative effects of repeated withdrawals affect

    decision making.

    Higher levels of impulsive decision making have been associated with early-onset

    alcoholism (Dom et al., 2006). Early-onset alcoholics have shown higher levels of impulsive

    decision making during a delayed discounting task than late-onset alcoholics and controls (Dom

    et al., 2006). This claim, however, needs to be further examined considering other factors

    related to poor decision making in early-onset alcoholism such as fewer years of education,

    potentially higher genetic load, or longer lifetime alcohol use.

    Neural correlates of decision making and risky behavior in alcoholism

    Behavioral aspects of alcoholism such as poor decision making and risky behavior have

    been associated with corresponding brain functional differences from non-substance abusing

    individuals. The executive control (principally mediated by cortical regions particularly in

    frontal cortex) and appetitive drive (principally mediated by striatal regions) brain networks

    have prominent roles in decision making and risky behavior in alcoholism. During its early

    stages, alcohol consumption is a goal-directed behavior, initiated and executed by regions

    within the executive control network (such as dorsolateral prefrontal cortex and anterior

    cingulate cortex) with its rewarding effects processed by appetitive drive regions (such as

    nucleus accumbens). After alcohol is repeatedly consumed, evidence for or consistent with

    poor decision making, consumption becomes more automatic (with more involvement of

    appetitive drive regions such as caudate and putamen) and less voluntary (with less

    involvement of executive control regions) (Everitt and Robbins, 2005). Alcohol consumption

    shifts to a more habitual mode, particularly as a response to avoid withdrawal symptoms. An

    individual with alcohol dependence seeks alcohol compulsively, a behavior that has been

    associated with increased activity of appetitive drive regions when presented with an alcohol

    cue, and a lack of engagement of prefrontal regions when required to stop a prepotent,

    maladaptive behavior such as alcohol consumption. The quality of interaction between and

    within these functional networks (frontal executive and striatal appetitive networks) is

  • Camchong, Endres, Fein 9

    becoming an increasingly relevant topic in alcoholism and addiction in general. Both the

    attenuation of the executive control and the enhancement of the appetitive drive networks are

    closely related to behavioral aspects of alcoholism such as poor decision making and

    subsequently risky behavior.

    To examine functional brain activity and synchrony associated with poor decision

    making in alcoholics, participants are required to perform tasks while functional magnetic

    resonance imaging (fMRI) data are collected. Numerous neuroimaging studies have used

    specific tasks to tap into functional brain differences associated with poor decision making and

    risky behavior during alcohol use, abuse and dependence.

    Brain function associated with decision making in binge-drinking

    A study by Xiao et al (2012) compared brain functional activity of 14 binge-drinking

    adolescents while they made decisions during the Iowa Gambling Task compared with 14

    adolescents who had never consumed alcohol. Binge drinkers had both behavioral and brain

    functional differences manifested as inflexible poor decision making (kept making

    disadvantageous decision) together with higher activity than non-drinkers in limbic brain

    regions known to play a role in the emotional aspects of decision making (amygdala and insula).

    Because they also found that adolescents that had higher limbic activity while performing the

    decision making task had more self-reported drinking problems, Xiao et al. (2012) proposed

    that a hyperactive bottom-up affective network may be a good candidate for a biological

    marker that can be used to identify individuals at risk of alcohol dependence. A previous

    behavioral study used the original Iowa Gambling Task and a variant of the Iowa Gambling Task

    to dissect whether poor decision- making found in binge-drinkers is attributable to insensitivity

    to long-term consequences (lack of executive control, planning) or to hypersensitivity to reward

    (enhanced appetitive drive) (Johnson et al., 2008). After comparing Iowa Gambling Task

    performance between adolescent binge-drinkers to adolescent never-drinkers, Johnson et al

    (2008) found that poor decision making in binge-drinkers is associated to hypersensitivity to

    reward. Results from these studies provide evidence that at early stages of alcohol abuse there

    is enhanced behavior ruled by appetitive drive together with a hyperactive bottom-up network.

  • Camchong, Endres, Fein 10

    Brain function associated with decision making in active drinkers with alcohol dependence

    The neural correlates of decision making have been examined in active drinkers with a

    diagnosis of alcohol dependence (Amlung et al., 2012). Amlung et al (2012) compared brain

    activity during delayed reward discounting between active drinkers with an alcohol dependence

    diagnosis (AUD+; n = 13) versus active drinkers without an alcohol dependence diagnosis (AUD-;

    n = 12). AUD+ showed more impulsive decision making and higher activity in executive control

    (dorsolateral prefrontal cortex) and attention (precuneus) regions than AUD- during delayed

    reward decisions. Although the study has a small sample size, was limited to men, but did

    compare drinkers with a control (non-drinking) group, this study provides important evidence

    of greater brain activity in executive control regions when alcoholics are required to delay

    gratifications, a finding that may reflect alcoholics’ increased demand of executive control

    when required to make decisions on behavior ruled by appetitive drive. These neural

    differences need to be explored further in larger samples that include a comparison to control

    groups.

    Brain function associated with decision making in short-term abstinent alcoholics

    Although it is important to understand the neural network differences in active drinkers,

    findings from these studies may be affected by the acute effects of alcohol and caution needs

    to be taken when comparing such results with those in abstinent treated samples. Active

    drinking samples may comprise a different population from treated samples - they may not

    have an alcohol use disorder (AUD) or have less severe AUDs than treatment samples (Fein and

    Landman, 2005, Di Sclafani et al., 2008, Fein et al., 2010a). The neural substrates of decision

    making have been extensively investigated in short-term abstinent alcoholics (STAA).

    Park et al (2010) compared brain activity during reward-guided decision making

    between 20 STAA with at least 7 days of abstinence (mean = 16.9 days of abstinence) and 16

    healthy controls. Subjects performed a task that required them to make a choice between two

    abstract stimuli to be allocated a probabilistically pre-determined reward. This task measured

    learning rates and outcome because subjects needed to update the reward values associated

    with the stimuli to guide their future responses. While STAA did not differ from controls in

  • Camchong, Endres, Fein 11

    striatal activity associated with predicting errors during task performance, they did show

    significantly lower fronto-striatal synchrony (i.e., ventral striatum and right dorsolateral

    prefrontal cortex) when presented with feedback of wins versus losses. Park et al (2010)

    suggest that while STAA do not have impaired brain activity associated with the representation

    of prediction error in the ventral striatum (nucleus accumbens), they do not seem to relay this

    information to brain regions that mediate higher executive control processes (dorsolateral

    prefrontal cortex - DLPFC) and are not able to integrate reward-related information for proper

    control of behavior following a reward (Park et al., 2010). While this study was limited to only

    men and to the examination of functional synchrony of the ventral striatum, it provides

    valuable evidence pointing to differences in functional synchrony between brain regions that

    mediate appetitive drive and regions that guide decision making in STAA versus healthy

    controls. The lack of interaction between these executive control and appetitive drive regions

    may underlie alcoholics’ difficulty in guiding future reward-related choices and goal-directed

    behavior. Furthermore, results from this study suggest that these neural network differences

    are evident after short periods of abstinence.

    A study by Li et al (2009) investigated differences in brain activity specifically related to

    impulsive control and risk-taking between 24 STAA and 24 healthy controls using the stop-

    signal task (SST). By dissecting the component processes of SST performance (response

    inhibition, error processing, post-error slowing, risk taking) they could examine neural

    differences specific to discrete aspects of impulse control and risky behavior. Authors reported

    that while groups did not differ in overall SST performance, STAA compared to healthy controls

    showed significantly (1) lower left DLPFC activity when inhibiting a response, (2) lower right

    DLPFC activity during post-error slowing (behavioral adjustment after an error), (3) lower

    amygdala, striatal, and posterior cingulate cortex activity during post-trial speeding

    (representing a risk-taking decision), and (4) higher activity in visual cortex and anterior

    cingulate cortex (ACC) when failing to stop a response. Results from this study showed that

    even though overall performance did not differ between groups, STAA showed differences in

    brain activity during individual trials that reflect specific instances of poor decision making such

    as post-trial speeding and failure to stop a response.

  • Camchong, Endres, Fein 12

    Evidence from studies mentioned above suggest that poor decision making and risky

    behavior in STAA are associated with brain functional differences in regions within the

    executive control (lower activity) and appetitive drive (higher activity) networks known to be

    involved in cognitive and emotional control. Whether these brain functional differences

    predispose to alcohol problems or are a consequence of unhealthy alcohol use is not clear.

    Brain function associated with decision making in individuals at risk for alcoholism

    Neuroimaging studies on adolescents at risk for alcoholism have identified brain

    functional differences associated with poor decision making in such samples. A study by

    Acheson et al (2009) compared brain function between 15 adolescents with a family history of

    alcoholism (FHP) and 19 with a negative family history of alcoholism (FHN) when performing

    the Iowa Gambling Task. While groups did not differ in behavioral performance, the FHP group

    showed more activity in left dorsal anterior cingulate cortex (ACC) and left caudate nucleus

    than the FHN group. Because activity in dorsal ACC has been associated with risk prediction

    and activity in caudate nucleus with risky responses, Acheson et al (2009) suggest that FHP

    need to recruit additional brain regions for proper decision making involving risk-taking when

    compared to FHN. A study by Cservenka et al (2012) provided a different perspective on

    predisposing biological markers of alcoholism. They investigated whether there were

    differences in functional activity associated with risk-taking when FHP versus FHN adolescents

    performed the “Wheel of Fortune” decision making task (WOF). While there were no

    behavioral differences in risk-taking, FHP showed significantly lower activity in right dorsolateral

    prefrontal cortex (DLPFC) and right cerebellar tonsil than FHN in the risky versus safe decision

    making contrast. Authors suggest that attenuated DLPFC response to risk-taking in FHP may be

    associated with poorer cognitive control and hence poorer behavioral regulation in FHP, making

    them vulnerable to failure in the decision to avoid risk-taking and ultimately contributing to out

    of control alcohol consumption.

    A study by Norman et al (2011) investigated the neural correlates of another aspect that

    contributes to risky behavior in adolescents, the lack of response inhibition. They examined

    brain function in adolescents while they performed a go/no-go task that measured response

  • Camchong, Endres, Fein 13

    inhibition and response selection. Based on follow-up interviews assessing alcohol use

    information (after a mean of 4.2 years), the sample was classified as either heavy alcohol users

    (n=21) or healthy controls (n=17). While there were no behavioral differences in impulse

    control during the go/no-go task at baseline, adolescents that later became heavy alcohol users

    showed significantly lower activity during no-go trials than healthy controls in prefrontal

    regions (inferior frontal gyrus, dorsolateral and medial frontal gyri), striatum (putamen) and

    inferior parietal lobules. The authors suggest that when required to exert control over a

    prepotent response, individuals that are at risk of becoming alcoholics show less responsive

    frontal regions even before the onset of drinking problems. Although these findings are

    important, they still do not provide decisive evidence for a predetermined predisposition

    because these may indicate that future problem drinkers have either (1) a pre-existing

    disadvantage (maybe genetic) due to poor engagement of frontal regions needed to properly

    exert executive control on impulsive and risky behaviors or (2) a delayed cortical maturity, in

    which activation in the executive control network is still not fully specialized yet, but never

    reaches its full potential because its development is later stunted by alcohol use. More studies

    need to be conducted to fully address these issues.

    Brain function associated with decision making in long-term abstinent alcoholics

    To investigate whether brain functional differences identified in actively drinking or

    recently abstinent alcoholics are permanent or can be overcome with long periods of

    abstinence, it is essential to examine long-term abstinent alcoholics. The examination of

    executive and appetitive drive networks during rest in long-term abstinent alcoholics (LTAA) has

    yielded results consistent with an ongoing compensatory mechanism in LTAA. A study by

    Camchong et al (2013a) that compared resting state synchrony of executive and appetitive

    drive networks between 23 LTAA (with more than 18 months of abstinence from alcohol use)

    and 23 healthy controls found that LTAA have (1) lower synchrony of appetitive drive regions

    and (2) greater synchrony of executive control regions than healthy controls. Moreover, these

    resting state synchrony differences were positively correlated with performance in a task that

    measured cognitive flexibility in decision making (e.g., higher resting state synchrony of

  • Camchong, Endres, Fein 14

    executive control regions significantly correlated with better performance). Results from this

    study reflect adaptive mechanisms in brain ongoing functional organization that may support

    proper executive control of behavior in long-term abstinent alcoholics and successfully stop

    behavior that may lead to relapse. A follow-up study by Camchong et al (2013b) that studied

    this effect in STAA (6-15 weeks of abstinence) found ordered effects from STAA to LTAA within

    both the executive control and appetitive drive networks: higher resting state synchrony of the

    executive control network (Figure 1) and lower resting state synchrony of the reward

    processing network (Figure 2) than healthy controls. These results provided further evidence

    that this compensatory mechanism follows an adaptive progression from short- to long-term

    abstinence. Longitudinal studies of brain functional organization need to be conducted to

    explore the hypothesis suggesting that synchrony within the executive control network

    progressively increases and synchrony within the appetitive drive network progressively

    decreases with length of abstinence.

    Differences in brain function and organization in prefrontal executive control regions are

    not specific to decision making and risky behavior in alcoholics. Alcoholics have shown similar

    differences as described above in neural activity in executive control regions (dorsolateral

    prefrontal cortex and anterior cingulate cortex) during tasks that hone in on other aspects of

    executive function such as spatial working memory (Pfefferbaum et al., 2001) or verbal working

    memory (Desmond et al., 2003, Cservenka and Nagel, 2012). Moreover, brain activity and

    functional organization differences associated with executive control differences have been

    identified in other samples with addiction to other substances such as cocaine and nicotine

    (Camchong et al., 2011, Gu et al., 2010, Janes et al., 2010).

    Although neuroimaging studies have identified brain function and organization

    differences in executive and appetitive drive networks in alcoholics, these differences vary

    depending on whether the alcoholic is actively drinking or has been abstinent for short or

    extended periods of time. A number of studies reviewed in the sections above do not show

    performance differences between alcoholic and comparison groups, but instead find

    differences between groups in brain activation patterns associated with comparable

  • Camchong, Endres, Fein 15

    performance. Such findings are often interpreted as indicating lack of efficiency in alcoholics vs.

    controls of specific brain regions in performing some function. However, it is important to

    remember that such a statement is a hypothesis, not a finding. If an impairment in some

    function is present (less efficient processing by a brain region is an impairment), there should

    be experimental challenges that will result in impaired performance on some task. A recent

    paper by Chanraud et al (2013) found that while controls and recovering alcoholics had similar

    performance levels during a spatial working memory task, they recruited different brain

    networks. While controls recruited prefrontal-cerebellar regions known to mediate working

    memory, recovering alcoholics recruited two additional fronto-cerebellar networks, presumably

    to compensate and achieve normal working memory performance (Chanraud et al., 2013). It is

    also important to emphasize that the phenomena discussed above are not necessarily reflected

    in all aspects of behavior. For example, Fein et al. (2004) found impaired performance on the

    Iowa Gambling Task in long-term abstinent alcoholics – they were able to achieve multi-year

    abstinence despite the persistent decision making impairments on the Iowa Gambling Task. In

    contrast, Fein et. al. (2006) found normal Iowa Gambling Task performance in actively drinking

    treatment naïve alcoholics. These individuals drank harmfully (a poor decision) despite having

    normal Iowa Gambling Task performance. These examples point out that propensities and

    inherited vulnerabilities do not fully control behavior. The research reviewed above suggests

    some of the adaptive changes that may take place in the development of alcoholism and in the

    struggle to achieve long-term abstinence.

  • Camchong, Endres, Fein 16

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