In the present study we found that even if binge drinkers and matched controls displayed a similar performance level in a working memory task, binge drinkers showed (i) higher bilateral activity in the pre-SMA; (ii) a positive correlation between the number of alcohol doses consumed per occasion and higher activity in the DMPFC region to execute the working memory condition (N2 vs. N0); and (iii) a positive correlation between the number of drinking occasions per week and higher activity in cerebello-thalamo-insular regions to perform in the working memory condition (N2 vs. N0).
Participants were challenged to an n-back working memory paradigm, contrasting N2 and N0 conditions. This task requires online monitoring, updating, and manipulation of remembered information and is therefore assumed to place great demands on a number of key processes within working memory 
. In agreement with previous studies, a conjunction analysis showed that frontoparietal areas as well as insula and precuneus were activated in both groups. The importance of frontal and parietal regions in working memory is largely undisputed. On the one hand, frontal regions have been implicated in numerous cognitive functions that are relevant to the n-back task, including monitoring and manipulation within working memory 
, holding non-spatial information on-line 
, the specification of retrieval cues 
, or “elaboration encoding” of information into episodic memory 
. On the other hand, parietal cortex is considered to be involved in the implementation of stimulus response mapping 
and in the storage of working memory contents 
as a kind of “buffer for perceptual attributes” 
. Also, the activation of precuneus during the visual working memory task is consistent with a recollection process aided by visual imagery 
, while insula activation is considered to be a part of the inferior fronto-parietal network, which responds to behaviorally relevant rather than to expected stimuli 
. This suggests an abstract role in extracting and processing task-relevant and salient information 
Analysis of the working memory tasks in binge and control subjects revealed that binge drinkers displayed increased BOLD responses in the pre-SMA (bilaterally) during the N2 condition but not the N0 task, while the controls did not. In other words, our data showed that greater activation was observed bilaterally in the pre-SMA in binge drinkers, while they displayed similar performances to controls. The pre-SMA is functionally known to be associated with more complex and cognitive controls when compared with the SMA 
. It has been suggested that activity in this region is related to the maintenance of visuospatial attention during working memory, a process that is likely to be particularly important where delays are imposed between a stimulus and a response to that stimulus 
. Such delays are, by definition, characteristic of the n-back tasks whereby a response is determined not by the presence of a particular stimulus alone, but by the presence of a stimulus that is identical in some predefined respect to one that has been presented n trials previously 
. Moreover, we found that the higher the number of alcohol doses per occasion, the more the DMPFC was activated in binge drinkers in the working-memory condition. These data suggest that participants who are accustomed to higher alcohol doses have to activate the DMPFC more to continue performing the task (i.e., in a brain region that seems to be crucial in attended stimulus perception 
and is well-known to be altered in chronic alcoholics 
). Also, we found that the more drinking occasions per week, the more we observed conjoint activation of portions of the thalamus, cerebellum and insula in binge drinkers during the working-memory condition. These data suggest that binge drinkers who consume alcohol more times per week have to strongly activate the cerebello-thalamo-insular regions (i.e., a set of brain regions well-known to be activated by covert shifts of attention, as the n-back task required subjects to continuously shift their focus from an external to an internal frame of reference in order to compare the identity of stimuli in working memory buffers to those presented externally) 
. Among these regions, it is worthwhile to note that the insula is seen as a key anatomical target for intervention to treat addiction, as this region is thought to integrate interoceptive states into conscious feelings (e.g., craving) and into decision-making processes that are involved in uncertain risk and reward 
. Thus, the study of this region in relation to the transition from controlled excessive consumption to alcohol dependence is highly relevant. Therefore, further experiments tagging the functioning of insula in binge drinkers may be useful to investigate whether, as compared to light drinkers, goal-directed decisions are hijacked by the activity of an impulsive system that intensifies motivation and weakens control on behavior.
Besides the potential concern linked to the fact that we have to rely on self-reported data to characterize the pattern of alcohol consumption of our participants, we are aware that a main problem of the present study is that we only reported group differences by using an uncorrected threshold (P<.001) with a minimum voxel clustering value of 100 voxels. Indeed, if, for a few datasets, this threshold may strike an appropriate balance between sensitivity and specificity, for others it cannot be appropriate, inducing therefore very different probabilities of false positives 
. In the present study, we used two groups of healthy, university students, confronted with a simple cognitive task: therefore, we expected that no strong differences, but only subtle modulations, could emerge. However, as false positives are difficult to refute once established in the literature, this danger should be minimized. In this view, as suggested by Bennett and colleagues 
, we presented in False Discovery Rate (FDR) values, in order that the reader can have a precise idea about the prevalence of false positives. With this mind, the present set of data should clearly be considered as preliminary. Nevertheless, besides the need for an independent replication of these results, we are convinced that the present data deserved attention. Young drinkers are often confused about what constitutes “an acceptable moderate consumption” and what damage they may actually be doing to their general health and/or brain. This may be due in part to ambiguous messages about potential positive medicinal effects of moderate alcohol consumption (e.g., reduced risk of heart attack; 
), and also to the fact that, up to now, alterations and behavioral deficits due to alcohol consumption have only been described after long term binge drinking 
. Our results suggest that in a very simple working memory task and in the absence of behavioral effect, binge drinking leads to brain modifications. We observed that binge drinkers recruited more neural activity at matched control performance levels. This supports earlier data suggesting that during more complex cognitive tasks, when a behavioral deficit is observable, brain “compensation strategies” might be engaged, consisting of concomitant reduction and increase of activity in distinct brain areas 
. However, we are totally aware that (1) in the present study, we did not find any relationship in binge drinkers between BOLD activity and working memory performance, so that any causal link between increased activity and performance can be drawn; and (2) it is not possible from the present study to completely discount the possibility that the differential effects observed for binge drinkers are pre-morbid in nature, i.e., existed prior to any alcohol consumption. In this view, further longitudinal studies should be designed in order to verify whether the emergence of brain differences in bingers followed (or not) the onset of drinking habits.
Also, even though positive correlations in specific brain regions were observed in binge drinkers between ADO/DOW values and the working memory condition (N2), the present data do not allow us to know whether the reported effects are caused
by alcohol intoxication, or by the pattern of binge drinking per se
(consisting in periods of intoxication followed by periods of abstinence), or both. Further studies should investigate this issue. For instance, a comparison of neural activity in young drinkers who consume the same amount of alcohol per week (for example, 28 doses), but with one group consuming these drinks in a regular way (four drinks each day), and the other group displaying a binge drinking pattern of consumption (14 doses in two different days of the week). In regard to our findings, it seems important to modify current information and prevention programs in order to impart the message that binge drinking is not just trivial social fun, but if continued, might favor the onset of cerebral disturbances. Moreover, these alterations in brain function can even occur at a stage at which behavioral manifestations are not yet observable
and may lead to alcohol dependence later in life. Indeed, several promising studies have recently discovered that enhanced drug cue-reactivity or cognitive processing of substance cues can be deliberately controlled or reduced 
. Finally, future studies on larger populations are needed to confirm our results, and longitudinal studies should be designed to explore the persistence of these brain changes when binge-drinking habits cease.