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

AbstractInstrumental 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.</jats:p

Freely Suspended, van der Waals Bound Organic Nanometer‐Thin Functional Films: Mechanical and Electronic Characterization

Determining the electronic properties of nanoscopic, low-dimensional materials free of external influences is key to discovery and understanding of new physical phenomena. An example is the suspension of graphene, which has allowed access to their intrinsic charge transport properties. Furthermore, suspending thin films enables their application as membranes, sensors, or resonators, as has been explored extensively. While the suspension of covalently-bound, electronically-active thin films is well established, semiconducting thin films composed of functional molecules only held together by van-der-Waals interactions could only be studied supported by a substrate. In the present work, it is shown that by utilizing a surface-crystallization method, electron conductive films with thicknesses of down to 6nm and planar chiral optical activity can be freely suspended across several hundreds of nm. The suspended membranes exhibit a Young's modulus of 2 to 13 GPa and are electronically decoupled from the environment, as established by temperature dependent field-effect transistor measurements

Biochemical, physiologic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial

Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiologic and clinical effects of L-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received L-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (PANSS, SANS, CDSS), cognition (MATRICS composite) and three complementary MRI measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared to placebo, L-methylfolate increased plasma methylfolate levels (d=1.00, p=.0009) and improved PANSS Total (d=.61, p=.03) as well as PANSS Negative and General Psychopathology subscales. While PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving L-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity, and increased cortical thickness. In conclusion, L-methylfolate supplementation was associated with salutary physiologic changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials

Amorfrutins are potent antidiabetic dietary natural products

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease

Amorfrutins are potent antidiabetic dietary natural products

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease