No abstract

A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional reactivity, and determining their predictive value for the development of frequent psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents are combined with functional genetics in animal and human models. Results will be validated in 1000 adolescents from the Canadian Saguenay Youth Study. The sample will be followed up longitudinally at the age of 16 years to investigate the predictive value of genetics and intermediate phenotypes for the development of frequent psychiatric disorders. This review describes the strategies the IMAGEN consortium used to meet the challenges posed by largescale multicentre imaging-genomics investigations. We provide detailed methods and Standard Operating Procedures that we hope will be helpful for the design of future studies. These include standardization of the clinical, psychometric and neuroimaging-acquisition protocols, development of a central database for efficient analyses of large multimodal data sets and new analytic approaches to large-scale genetic neuroimaging analyses.

We test the hypothesis that motivational and cognitive processes are linked by a specific neural system to reach maximal efficiency. We studied six normal subjects performing a working memory paradigm (n-back tasks) associated with different levels of monetary reward during an fMRI session. The study showed specific brain activation in relation with changes in both the cognitive loading and the reward associated with task performance. First, the working memory tasks activated a network including the dorsolateral prefrontal cortex [Brodmann area (BA) 9͞46] and, in addition, in the lateral frontopolar areas (BA 10), but only in the more demanding condition (3-back task). This result suggests that lateral prefrontal areas are organized in a caudo-rostral continuum in relation with the increase in executive requirement. Second, reward induces an increased activation in the areas already activated by working memory processing and in a supplementary region, the medial frontal pole (BA 10), regardless of the level of cognitive processing. It is postulated that the latter region plays a specific role in monitoring the reward value of ongoing cognitive processes. Third, we detected areas where the signal decreases (ventral-BA 11͞47 and subgenual prefrontal cortices) in relation with both the increase of cognitive demand and the reward. The deactivation may represent an emotional gating aimed at inhibiting adverse emotional signals to maximize the level of performance. Taken together, these results suggest a balance between increasing activity in cortical cognitive areas and decreasing activity in the limbic and paralimbic structures during ongoing higher cognitive processing.