The results from our VBM ROI analysis revealed that long-term abstinent alcoholics who show impairment on the SGT also show bilateral reduction of gray matter in the area of the amygdala when compared to controls. There was no evidence of differential gray matter reduction between abstinent alcoholics and controls within the VMPFC. These findings suggest that the decision-making deficits in these long-term abstinent alcoholics may reflect an abnormality in brain structure. This structurally based abnormality may be the result of long-term alcohol abuse or dependence. We have shown in a previous paper that active alcoholics have a reduction of gray matter in other areas of the brain (Fein et al., 2002
). This paper goes one step further and demonstrates that there are specific areas of reduced gray matter that exist even in multi-year abstinent alcoholics when sensitive analytic methods (SPM2 with skull-stripping) are used and the analyses are restricted to the examination of specific structures. It is also possible that these brain structure abnormalities reflect a pre-existing condition that could predispose one to severe alcoholism. Individuals with a high genetic-loading for alcoholism may “start out” with a smaller amygdala, thus putting them at a disadvantage in the area of decision-making.
We did not find any association between gray matter in the ROIs and duration of abstinence. In our manuscript reporting gambling task impairments in the samples presented here (Fein et al., 2004b
), and in a manuscript on cognitive function in these same subjects (Fein et al., in press
), we did not find any associations between performance and duration of abstinence. In the cognition paper, we found that AbsAlc were essentially cognitively normal (except for impairments in spatial functioning which had to be interpreted gingerly because it was the only domain with impairment of 9 domains assessed – yet it was among the domains that are most frequently reported to be impaired in alcoholism and drug addiction (Crews et al., 2005
; Munro et al., 2000
; Oscar-Berman et al., 1997
; Sullivan et al., 2002
; Sullivan and Pfefferbaum, 2005
). Nonetheless, we found no association between SGT performance and spatial processing ability. We interpreted the essentially intact cognitive performance of this sample (Fein et al., in press
) and the lack of correlation between cognitive performance and abstinence duration as indicating that most of the cognitive recovery had already taken place by six months to one year of abstinence. As for the gambling task performance and for the reduced amygdalar gray matter finding reported here, we interpret the lack of association with duration of abstinence as being consistent with both of these phenomena reflecting predisposing factors that were present before active alcoholism occurred.
We observed gray matter reductions in the amygdala, but not in the VMPFC. Previous research indicates that disadvantageous decision-making on the SGT can be associated with gray matter reductions in either the VMPFC or the amygdala (Bechara et al., 1999
). Bechara and colleagues observed decision-making deficits in patients with focal VMPFC lesions and patients with bilateral amygdalar lesions. While VMPFC and amygdalar lesions both were associated with similar overall impairments in SGT performance, the patterns of somatic activity associated performance differed between the two groups. Patients with amygdalar lesions did not generate skin conductance responses after rewards or losses, while VMPFC patients did generate such responses (Bechara et al., 1999
). Bechara and colleagues (2003
propose that deficits in amygdalar function are associated with deficits in attaching emotional valence to motivationally significant events (i.e., a lack of anxiety – negative affect after experiencing loss), while VMPFC deficits are associated with problems effectively integrating somatic state information from the amygdala and other brain structures prior to executing a choice. This formulation is consistent with research that implicates the amygdala in the experience of emotion, or more specifically with the attachment of emotional valence to specific events (Aggleton and Mishkin, 1986
; Boulis and Davis, 1989
; LeDoux et al., 1990
). Individuals with increased amygdalar activity are disposed to develop anxiety disorders (Schwartz et al., 2003
), while those with amygdalar lesions fail to develop classically conditioned fear responses (Davis, 1989
Abnormalities in the amygdala have also been related to anxiety disorders, such as social anxiety and PTSD, as well as a general behavioral inhibition in childhood (Pitman et al., 2001
; Schwartz et al., 2003
). However, anxiety disorders appear to be associated with increased amygdalar activation, while our data suggests that some cases of alcoholism are associated with decreased amygdala volumes. It is a reasonable hypothesis that this decreased volume is also associated with reduced amygdalar activation. Individuals with increased amygdalar activity are disposed to develop anxiety disorders (Schwartz et al., 2003
), while those with lesions in the amygdala fail to develop classically conditioned fear responses (Davis, 1989
) and may be more vulnerable to externalizing disorders (Patrick, 1994
). The gray matter reductions in the amygdala observed in our sample of alcoholics is consistent with theory and research suggesting that the decision-making problems observed in alcoholics and other substance abusers are associated with differences in basic motivational processes affecting approach – avoidance behavior (Finn, 2002
). Substance abusers prefer immediate over long-term rewards (Kirby et al., 1999
; Kollins, 2003
; Mitchell, 1999
), have problems inhibiting behavior to avoid punishment when engaged in reward-seeking behavior (Finn et al., 2002
), and show evidence of increased attention to rewards on the SGT task (Bechara et al., 2002
; Finn, 2002
; Stout et al., 2004
). Further research should investigate the association between amygdala volume and function, SGT decision-making deficits, and decision-making problems in these populations in other areas of life, such as sexual behavior, finances, work-related behaviors, eating behaviors, interpersonal conflict, emotion-provoking situations, and other contexts that are motivationally relevant to the individual.
Poor decision-making also can be associated with hippocampal damage, however the specific mechanisms and patterns of poor decision-making associated with amygdalar and hippocampal lesions are different. While Bechara et al (2003)
reported that amygdalar lesion patients made more disadvantageous decisions relative to controls, they note that those amygdalar patients that had intact hippocampal structures made more disadvantageous decisions than amygdalar patients who also had hippocampal damage. The decisions of patients with hippocampal damage, who had an amnestic syndrome, were more random, suggesting that memory for previous trials was not being accessed to guide the decision on the current trial. On the other hand memory appeared to guide the decisions of amygdalar patients with spared hippocampal areas, who were clearly biased to continue to draw from the disadvantageous decks, presumably because they were not responding with negative emotion to the large losses associated with disadvantageous deck choices.
We also feel that it is worthwhile to investigate possible differences in brain structure among individuals with and without a high family history for alcoholism, as well as those who go on to acquire the addiction and those who do not. Furthermore, we are currently involved in a project that hopes to investigate alcohol abuse/dependence in its earliest stages. Information from these studies could aid in deciphering whether or not structural brain abnormalities are a contributing factor to or a result of alcohol abuse.
From an image analysis perspective, this work demonstrates the increased sensitivity that results from using skull stripped inputs and from restricting the analysis to a ROI. Without both of these methodological advances, no statistically significant finding would have been forthcoming from this work