No abstract

Background-Psychopathic behavior is generally attributed to a fundamental, amygdala-mediated deficit in fearlessness that undermines social conformity. An alternative view is that psychopathy involves an attention-related deficit that undermines the processing of peripheral information including fear stimuli.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attentiondeficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

Previous work using gambling tasks indicate that the feedback negativity (FN) reflects primary or salient stimulus attributes (often gain vs. loss), whereas the feedback-P300 appears sensitive to secondary stimulus information. A recent time-frequency approach has characterized separable theta (3–7 Hz) and delta (0–3 Hz) feedback processes, independently sensitive to primary feedback attributes, specifically loss and gain outcomes respectively (Bernat et al., 2011). The current study extends this time-frequency work to evaluate both primary and secondary (relative outcome and outcome magnitude) feedback attributes. Consistent with previous reports, theta indexed an initial, lower-level response sensitive to the primary (most salient) feedback attributes (specifically losses), while delta was sensitive to both primary attributes (specifically gains) and assessed secondary stimulus features.

Our previous research demonstrated that psychopathy-related fear deficits involve abnormalities in attention that undermine sensitivity to peripheral information. In the present study, we specified this attention-mediated abnormality in a new sample of 87 prisoners assessed with Hare's Psychopathy Checklist-Revised (Hare, 2003). We measured fear-potentiated startle (FPS) under four conditions that crossed attentional focus (threat vs. alternative) with early versus late presentation of threat cues. The psychopathic deficit in FPS was apparent only in the early-alternative-focus condition, in which threat cues were presented after the alternative goal-directed focus was established. Furthermore, psychopathy interacted with working memory capacity in the late-alternative-focus condition, which suggests that individuals high in psychopathy and working memory capacity were able to maintain a set-related alternative focus that reduced FPS. The results not only provide new evidence that attention moderates the fearlessness of psychopathic individuals, but also implicate an early attention bottleneck as a proximal mechanism for deficient response modulation in psychopathy.