Neural correlates of learning accommodation and consolidation in generalised anxiety disorder.

OBJECTIVE.: Anxiety can interfere with attention and working memory, which are components that affect learning. Statistical models have been designed to study learning, such as the Bayesian Learning Model, which takes into account prior possibilities and behaviours to determine how much of a new behaviour is determined by learning instead of chance. However, the neurobiological basis underlying how anxiety interferes with learning is not yet known. Accordingly, we aimed to use neuroimaging techniques and apply a Bayesian Learning Model to study learning in individuals with generalised anxiety disorder (GAD). METHODS.: Participants were 25 controls and 14 individuals with GAD and comorbid disorders. During fMRI, participants completed a shape-button association learning and reversal task. Using a flexible factorial analysis in SPM, activation in the dorsolateral prefrontal cortex, basal ganglia, and hippocampus was compared between groups during first reversal. Beta values from the peak of these regions were extracted for all learning conditions and submitted to repeated measures analyses in SPSS. RESULTS.: Individuals with GAD showed less activation in the basal ganglia and the hippocampus only in the first reversal compared with controls. This difference was not present in the initial learning and second reversal. CONCLUSION.: Given that the basal ganglia is associated with initial learning, and the hippocampus with transfer of knowledge from short- to long-term memory, our results suggest that GAD may engage these regions to a lesser extent during early accommodation or consolidation of learning, but have no longer term effects in brain activation patterns during subsequent learning.

Transient attention equally reduces visual crowding in radial and tangential axes.

Crowding refers to the failure to identify a peripheral object due to its proximity to other objects (flankers). This phenomenon can lead to reading and object recognition impairments and is associated with macular degeneration, amblyopia, and dyslexia. Crucially, the maximal target-flanker spacing required for the crowding interference (critical spacing) increases with eccentricity. This spacing is also larger when target and flankers appear along the horizontal meridian (radial arrangement) than when the flankers appear above and below the target (tangential arrangement). This phenomenon is known as radial-tangential anisotropy. Previous studies have demonstrated that transient attention can reduce crowding interference; however, it is still unclear whether and how attention interacts with radial-tangential anisotropy. To address this issue, we manipulated transient attention by using a cue at either the target (valid) or the fixation (neutral) location, in both radial and tangential target-flanker arrangements. Results showed that critical spacing was larger in the radial than in the tangential arrangement and that cueing the target location improved performance and reduced the critical spacing for both radial and tangential arrangements to the same extent. Together, our findings suggest that transient spatial attention plays an essential role in crowding but not in radial-tangential anisotropy.

Dimensional Affective Processing in BD.

Bipolar Disorder (BD) involves altered neural affective processing, but studies comparing BD patients to controls have yielded inconsistent results. This might relate to substantial variability in the nature and severity of mood symptoms among individuals with BD. Hence, we dimensionally examined the relationship between depressive and manic symptom severity and neural responses to positive and negative affective stimuli. 39 Participants with BD completed measures of depression and mania severity prior to completing a cognitive-affective processing task during fMRI. A multiple regression model was run in SPM to identify brain regions correlated with depressive and manic symptoms during positive-neutral and negative-neutral contrasts. A-priori anatomical ROIs were defined bilaterally in frontal, parietal and limbic regions. Results showed that depression severity was associated with increased activation in frontal, parietal, and limbic ROIs, regardless of valence. Mania severity was correlated with both increased and decreased activation, particularly within frontal subdivisions and during the processing of positively valenced images. In conclusion, dimensional modeling of symptom severity captures variance in neural responses to affect, which may have been previously undetected due to heterogeneity when examined at the group level. Future fMRI studies comparing BD patients and controls should account for symptom variability in BD.

Investigating Motor Preparation in Autism Spectrum Disorder With and Without Attention Deficit/Hyperactivity Disorder.

This study investigated motor preparation and action-consequence prediction using the lateralized readiness potential (LRP). Motor impairments are common in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. Alterations in predictive processes may impact motor planning. Whether motor planning deficits are characteristic of ASD broadly or magnified in the context of co-morbid ADHD is unclear. ASD children with (ASD + ADHD; n = 12) and without (ASD - ADHD; n = 9) comorbid ADHD and typical controls (n = 29) performed voluntary motor actions that either did or did not result in auditory consequences. ASD - ADHD children demonstrated LRP enhancement when their action produced an effect while ASD + ADHD children had attenuated responses regardless of action-effect pairings. Findings suggest influence of ADHD comorbidity on motor preparation and prediction in ASD.

Neural basis of associative learning in Trichotillomania and skin-picking disorder.

Disorders such as Trichotillomania (TTM) and skin-picking disorder (SPD) are associated with reduced flexibility and increased internally focused attention. While the basal ganglia have been hypothesized to play a key role, the mechanisms underlying learning and flexible accommodation of new information is unclear. Using a Bayesian Learning Model, we evaluated the neural basis of learning and accommodation in individuals with TTM and/or SPD. Participants were 127 individuals with TTM and/or SPD (TTM/SPD) recruited from three sites (age 18-57, 84% female) and 26 healthy controls (HC). During fMRI, participants completed a shape-button associative learning and reversal fMRI task. Above-threshold clusters were identified where the Initial Learning-Reversals BOLD activation contrast differed significantly (p < .05 FDR-corrected) between the two groups. A priori, effects were anticipated in predefined ROIs in bilateral basal ganglia, with exploratory analyses in the hippocampus, dorsolateral prefrontal cortex (dlPFC), and dorsal anterior cingulate cortex (dACC). Relative to HC, individuals with TTM/SPD demonstrated reduced activation during initial learning compared to reversal learning in the right basal ganglia. Similarly, individuals with TTM/SPD demonstrated reduced activation during initial learning compared to reversal learning in several clusters in the dlPFC and dACC compared to HC. Individuals with TTM/SPD may form or reform visual stimulus-motor response associations through different brain mechanisms than healthy controls. The former exhibit altered activation within the basal ganglia, dlPFC, and dACC during an associative learning task compared to controls, reflecting reduced frontal-subcortical activation during initial learning. Future work should determine whether these neural deficits may be restored with targeted treatment.

Neural correlates of citalopram and placebo response in acute bipolar depression: A randomized trial.

While serotonin reuptake inhibitors are sometimes used in clinical practice to treat acute bipolar depression, the neurophysiological substrates underlying their efficacy are little studied. In the context of a larger clinical efficacy trial, the present study explored neural mechanisms associated with citalopram versus placebo treatment for bipolar depression. FDG-PET imaging examined whole-brain metabolic changes before and after treatment. Clinical efficacy was similar for citalopram versus placebo. Neuroimaging results demonstrated greater glucose metabolism in the left orbitofrontal cortex (OFC) before treatment (combined citalopram and placebo subjects) relative to after treatment, but did not correlate with clinical recovery. Glucose metabolism in the left OFC was also a predictor of depression severity when baseline scans were regressed with baseline MADRS scores. Despite of our small sample size and possibly underpowered whole-brain analysis approach, these preliminary results suggest the OFC, a key region involved in reward circuity, may be a neural substrate for depressive symptom improvement in bipolar depression, regardless of whether due to active treatment or placebo.