A decrease in interaction between brain regions is observed in individuals with autism spectrum disorder (ASD), which is believed to be related to restricted neural network access in ASD. Propranolol, a beta-adrenergic antagonist, has revealed benefit during performance of tasks involving flexibility of access to networks, a benefit also seen in ASD. Our goal was to determine the effect of propranolol on functional connectivity in ASD during a verbal decision making task as compared to nadolol, thereby accounting for the potential spurious fMRI effects due to peripheral hemodynamic effects of propranolol. Ten ASD subjects underwent fMRI scans after administration of placebo, propranolol or nadolol, while performing a phonological decision making task. Comparison of functional connectivity between pre-defined ROI-pairs revealed a significant increase with propranolol compared to nadolol, suggesting a potential imaging marker for the cognitive effects of propranolol in ASD.

Background Major depressive disorder is a leading cause of disability worldwide; however, little is known about pathological mechanisms involved in its development. Research in adolescent depression has focused on reward sensitivity and striatal mechanisms implementing it. The contribution of loss sensitivity to future depression, as well as the orbitofrontal cortex (OFC) mechanisms critical for processing losses and rewards, remain unexplored. Furthermore, it is unclear whether OFC functioning interacts with familial history in predicting future depression. Methods In this longitudinal study we recorded functional magnetic resonance imaging (fMRI) data while 229 adolescent females with or without parental history of depression completed a monetary gambling task. We examined if OFC blood-oxygen-level-dependent (BOLD) response and functional connectivity during loss and win feedback was associated with depression symptoms concurrently and prospectively (9 months later), and whether this relationship was moderated by parental history of depression. Results Reduced OFC response during loss was associated with higher depression symptoms concurrently and prospectively, even after controlling for concurrent depression, specifically in adolescents with parental history of depression. Similarly, increased OFC-posterior insula connectivity during loss was associated with future depression symptoms but this relationship was not moderated by parental history of depression. Conclusions This study provides the first evidence for loss-related alterations in OFC functioning and its interaction with familial history of depression as possible mechanisms in the development of depression. While the current fMRI literature has mainly focused on reward, the present findings underscore the need to include prefrontal loss processing in existing developmental models of depression.

Individuals with autism spectrum disorders (ASD) demonstrate impaired utilization of context, which allows for superior performance on the "false memory" task. We report the application of a simplified parallel distributed processing model of context utilization to the false memory task. For individuals without ASD, experiments support a model wherein presentation of one word, e.g., ''apple,'' strongly activates the neighboring nodes of closely related words such as ''fruit,'' ''tree,'' whereas in ASD these neighboring nodes are relatively less activated. We demonstrate this model to be consistent with the superior performance on recognition testing on the false memory test, but not on free recall. This may have an anatomic basis in diminished hippocampal neuronal arborization and the abnormal minicolumnar pathology in ASD.

Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal. Eight subjects in acute cocaine withdrawal were compared to controls for connectivity in language areas while performing a task involving categorization of words according to semantic and phonological relatedness. Acute withdrawal subjects had significantly less overall connectivity during semantic relatedness, and a trend towards less connectivity during phonological relatedness. Of potential future interest is whether this might serve as an imaging marker for treatment in patients.