A Cross-Sectional Study of Dietary and Genetic Predictors of Blood Folate Levels in Healthy Young Adults.

Since 1998, the U.S. has mandated folic acid (FA) fortification of certain grain products to reduce the risk of neural tube defects. Folate intake and red blood cell (RBC) folate concentrations increased substantially post-intervention, although recent studies raise concerns about the level of ongoing benefit. This study investigated blood folate level determinants in healthy young adults, including intake of naturally occurring food folate, synthetic FA, and the interaction of naturally occurring food folate with a common missense variant in the FOLH1 gene thought to affect absorption. Participants (n = 265) completed the Diet History Questionnaire II, RBC folate testing, and were genotyped for the 484T>C FOLH1 variant. Men reported significantly greater intake of all folate sources except for supplemental FA, but RBC folate levels did not significantly differ by sex. Synthetic FA was a stronger predictor of RBC folate than naturally occurring food folate. In the largest racial group, synthetic FA and the interaction of FOLH1 genotype with naturally occurring food folate significantly predicted RBC folate, with the overall model accounting for 13.8% of the variance in RBC folate levels. Blood folate levels rely on a complex interaction of natural and synthetic folate intake as well as FOLH1 genotype.

Neural determinants of human goal-directed vs. habitual action control and their relation to trait motivation.

Instrumental learning is mediated by goal-directed and habit systems in the brain. While rodent studies implicate distinct prefrontal/striatal regions in goal-directed and habit learning, neural systems underpinning these two processes in humans remain poorly understood. Here, using a validated discrimination learning task that distinguishes goal-directed learning from habit learning in 72 subjects in fMRI, we investigated the corticostriatal correlates of goal-directed learning and tested whether brain activation during learning is associated with trait motivation and behavioral performance in the post-learning test phase. Participants showed enhanced activation in medial prefrontal and posterior cingulate cortices during goal-directed action selection in the training phase, whereas habitual action selection activated bilateral insula, bilateral dorsal caudate and left precentral gyrus. In addition, early phase of learning was associated with increased activation in the frontoparietal control network and dorsal striatum, whereas default mode regions depicted increased activation in the late phase. Finally, avoidance motivation scores measured by Behavioral Inhibition/Activation System (BIS/BAS) correlated with accuracy during goal-directed learning and showed a nominally significant correlation with activation in dorsomedial prefrontal cortex during goal-directed acquisition of stimuli. These findings reveal the temporal dynamics of instrumental behavior and suggest that avoidance motivation predicts performance and brain activity during goal-directed learning.

Dopamine D1 signaling organizes network dynamics underlying working memory.

Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.

Disrupted Working Memory Circuitry in Schizophrenia: Disentangling fMRI Markers of Core Pathology vs Other Aspects of Impaired Performance.

Working memory (WM) impairment, a core feature of schizophrenia, is often associated with aberrant dorsolateral prefrontal cortex (dlPFC) activation. Reduced resting-state connectivity within the frontoparietal control network (FPCN) has also been reported in schizophrenia. However, interpretation of WM-related dlPFC dysfunction has been limited by performance differences between patients and controls, and by uncertainty over the relevance of resting-state connectivity to network engagement during task. We contrasted brain activation in 40 schizophrenia patients and 40 controls during verbal WM performance, and evaluated underlying functional connectivity during rest and task. During correct trials, patients demonstrated normal FPCN activation, despite an inverse relationship between positive symptoms and activation. FPCN activation differed between the groups only during error trials (controls>patients). In contrast, controls demonstrated stronger deactivation of the ventromedial prefrontal cortex (vmPFC) during correct and error trials. Functional connectivity analysis indicated impaired resting-state FPCN connectivity in patients, but normal connectivity during task. However, patients showed abnormal connectivity among regions such as vmPFC, lateral orbitofrontal cortex, and parahippocampal gyrus (PHG) during both rest and task. During task, patients also exhibited altered thalamic connectivity to PHG and FPCN. Activation and connectivity patterns that were more characteristic of controls generally correlated with better performance. In summary, patients demonstrated normal FPCN activation when they remained on-task, and exhibited normal FPCN connectivity during WM, whereas vmPFC deactivation differences persisted regardless of WM performance. Our findings suggest that altered FPCN activation in patients reflects performance difference, and that limbic and thalamic dysfunction is critically involved in WM deficits in schizophrenia.

Neural predictors of successful brief psychodynamic psychotherapy for persistent depression.

BACKGROUND: Psychodynamic psychotherapy has been used to treat depression for more than a century. However, not all patients respond equally well, and there are few reliable predictors of treatment outcome. METHODS: We used resting (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) scans immediately before and after a structured, open trial of brief psychodynamic psychotherapy (n = 16) in conjunction with therapy process ratings and clinical outcome measures to identify neural correlates of treatment response. RESULTS: Pretreatment glucose metabolism within the right posterior insula correlated with depression severity. Reductions in depression scores correlated with a pre- to posttreatment reduction in right insular metabolism, which in turn correlated with higher objective measures of patient insight obtained from videotaped therapy sessions. Pretreatment metabolism in the right precuneus was significantly higher in patients who completed treatment and correlated with psychological mindedness. CONCLUSIONS: Resting brain metabolism predicted both clinical course and relevant psychotherapeutic process during short-term psychodynamic psychotherapy for depression.