STRUCTURAL NEUROIMAGING AND THE ANTISOCIAL BRAIN Main Findings and Methodological Challenges STÉPHANE A. DE BRITO, University College London; SHEILAGH HODGINS, King’s College London; EAMON J. P. MCCRORY, University College London; ANDREA MECHELLI, King’s College London; MARKO WILKE, University of Tübinge;, ALICE P. JONES; ESSI VIDING, University College London Abstract A series of neuroimaging studies have reported structural differences in several subcortical and frontal systems in individuals with stable antisocial behavior (sASB). Specifically, differences have been observed in the prefrontal and temporal cortices (e.g., amygdala and hippocampus). However, the sASB population is typically characterized by co-occurring hyperactivity– inattention symptoms and low cognitive ability. These nuisance variables are likely to complicate the interpretation of findings regarding structural differences associated with sASB. The way in which each study deals with these variables influences the conclusions that can be drawn about the brain structure and function of children and adults with sASB. This article briefly reviews the extant literature in this field before considering two approaches that may be used to deal with comorbidities conceptualized as nuisance variables--namely, the analysis of covariance (ANCOVA) and the matched-group design. Then, the authors illustrate, with their own data, checks that may be performed to ensure the validity of results using ANCOVA. Keywords: neuroimaging; antisocial brain; antisocial behavior Following recent advances in structural magnetic resonance imaging (sMRI), the investigation of structural brain differences associated with stable antisocial behavior (sASB) in adults and children has been the focus of several studies (Bufkin & Luttrell, 2005; Raine, Lencz, Bihrle, LaCasse, & Colletti, 2000; Vloet, Konrad, Huebner, Herpertz, & Herpertz- Dahlmann, 2008). We first review the salient findings from this literature before considering the methodological challenges inherent in attributing these structural brain differences to the presence of sASB. Given the frequency of comorbid symptomatology and the cognitive differences typically associated with sASB, researchers must contend with the inherent disadvantages of a quasi-experimental design. We briefly review two approaches that may be used to deal with comorbidities conceptualized as nuisance variables—namely, the analysis of covariance (ANCOVA) and the matched-group design—then we illustrate, with our own data, checks that may be performed to ensure the validity of results using ANCOVA. Note that this study does not cover in detail the underlying methodological and statistical considerations pertaining to ANCOVA and matched-group design (for a thorough discussion of these topics, see Meehl, 1970; Miller & Chapman, 2001; Shadish, Cook, & Campbell, 2002). Instead, the current aim is to draw attention to important methodological and conceptual considerations when using the ANCOVA and matched-group approaches to deal with nuisance variables in brain-imaging studies of individuals presenting sASB. Finally, implications are considered for researchers and clinicians who are conducting and interpreting results from neuroimaging studies of persons with sASB. Criminal Justice and Behavior (2009), 36, 1173-1186 DOI: 10.1177/0093854809342883 The online version of this article can be found at: http://cjb.sagepub.com/content/36/11/1173