Role Of The Dorsal Striatum In Learning and Decision Making

The striatum, the input region of the basal ganglia, has been shown to mediate many cognitive functions. The striatum itself can be functionally segregated into dorsal (DS) and ventral striatum (VS). For more than 60 years, DS has been reported to mediate stimulus-response learning, though evidence has been accruing pointing to a role in decision making. These literatures have been growing independently and an aim of this thesis was to bridge these two bodies of knowledge. We directly investigated the role of DS in stimulus-response learning versus decision making using functional magnetic resonance imaging (fMRI) in patients with Parkinson’s disease (Chapter 2) and obsessive compulsive disorder (Chapter 3). In Chapter 4, the role of DS in stimulus-response habit learning was tested in healthy individuals using fMRI. In three separate experiments (Chapters 2-4), all of the results strongly support the notion that DS mediates decision making and not learning. DS is implicated in many disorders ranging from Parkinson’s disease, obsessive compulsive disorder and addiction, and clarifying the role of DS in cognitive function is paramount for understanding substrates of disease and developing treatments

Functional role of the striatum in stimulus-response learning: Evidence from functional MRI and patients with Parkinson\u27s disease

Cognitive impairment is recognized in Parkinson’s disease (PD). Understanding striatum-mediated cognitive functions will help elucidate some of these abnormalities. Learning is often impaired by dopaminergic medication. However, dorsal striatum (DS) has been implicated in learning; an unexpected result given that dopaminergic therapy, the gold standard treatment for PD, remediates DS functioning. In two separate experiments, stimulus-response association learning and decision-making were examined in healthy individuals using functional magnetic resonance imaging (fMRI), and in PD patients using behavioural methods. In Experiment 1, healthy individuals completed a stimulus-response learning task, and brain regions associated with learning versus decision-making were investigated using fMRI. In Experiment 2, patients with PD completed a similar task on and off their dopaminergic medication. Results from both experiments suggest that DS mediates decision-making and not learning. This greater understanding of striatum-mediated cognition will ultimately prompt clinicians to devise medication strategies that consider both motor and cognitive symptoms of PD

Spatially resolved ultrafast precessional magnetization reversal

Spatially resolved measurements of quasi-ballistic precessional magnetic switching in a microstructure are presented. Crossing current wires allow detailed study of the precessional switching induced by coincident longitudinal and transverse magnetic field pulses. Though the response is initially spatially uniform, dephasing occurs leading to nonuniformity and transient demagnetization. This nonuniformity comes in spite of a novel method for suppression of end domains in remanence. The results have implications for the reliability of ballistic precessional switching in magnetic devices.Comment: 17 pages (including 4 figures), submitted to Phys. Rev. Let

Endothelial cell injury by high glucose and heparanase is prevented by insulin, heparin and basic fibroblast growth factor

BACKGROUND: Uncontrolled hyperglycemia is the main risk factor in the development of diabetic vascular complications. The endothelial cells are the first cells targeted by hyperglycemia. The mechanism of endothelial injury by high glucose is still poorly understood. Heparanase production, induced by hyperglycemia, and subsequent degradation of heparan sulfate may contribute to endothelial injury. Little is known about endothelial injury by heparanase and possible means of preventing this injury. OBJECTIVES: To determine if high glucose as well as heparanase cause endothelial cell injury and if insulin, heparin and bFGF protect cells from this injury. METHODS: Cultured porcine aortic endothelial cells were treated with high glucose (30 mM) and/or insulin (1 U/ml) and/or heparin (0.5 μg/ml) and /or basic fibroblast growth factor (bFGF) (1 ng/ml) for seven days. Cells were also treated with heparinase I (0.3 U/ml, the in vitro surrogate heparanase), plus insulin, heparin and bFGF for two days in serum free medium. Endothelial cell injury was evaluated by determining the number of live cells per culture and lactate dehydrogenase (LDH) release into medium expressed as percentage of control. RESULTS: A significant decrease in live cell number and increase in LDH release was found in endothelial cells treated with high glucose or heparinase I. Insulin and/or heparin and/or bFGF prevented these changes and thus protected cells from injury by high glucose or heparinase I. The protective ability of heparin and bFGF alone or in combination was more evident in cells damaged with heparinase I than high glucose. CONCLUSION: Endothelial cells injured by high glucose or heparinase I are protected by a combination of insulin, heparin and bFGF, although protection by heparin and/or bFGF was variable

Dorsal striatum mediates deliberate decision making, not late-stage, stimulus–response learning

We investigated a controversy regarding the role of the dorsal striatum (DS) in deliberate decision-making versus late-stage, stimulus–response learning to the point of automatization. Participants learned to associate abstract images with right or left button presses explicitly before strengthening these associations through stimulus–response trials with (i.e., Session 1) and without (i.e., Session 2) feedback. In Session 1, trials were divided into response-selection and feedback events to separately assess decision versus learning processes. Session 3 evaluated stimulus–response automaticity using a location Stroop task. DS activity correlated with response-selection and not feedback events in Phase 1 (i.e., Blocks 1–3), Session 1. Longer response times (RTs), lower accuracy, and greater intertrial variability characterized Phase 1, suggesting deliberation. DS activity extinguished in Phase 2 (i.e., Blocks 4–12), Session 1, once RTs, response variability, and accuracy stabilized, though stimulus–response automatization continued. This was signaled by persisting improvements in RT and accuracy into Session 2. Distraction between Sessions 1 and 2 briefly reintroduced response uncertainty, and correspondingly, significant DS activity reappeared in Block 1 of Session 2 only. Once stimulus–response associations were again refamiliarized and deliberation unnecessary, DS activation disappeared for Blocks 2–8, Session 2. Interference from previously learned right or left button responses with incongruent location judgments in a location Stroop task provided evidence that automaticity of stimulus–specific button-press responses had developed by the end of Session 2. These results suggest that DS mediates decision making and not late-stage learning, reconciling two, independently evolving and well-supported literatures that implicate DS in different cognitive functions. Hum Brain Mapp 38:6133–6156, 2017. © 2017 Wiley Periodicals, Inc

Update to ACTE II TechPort Web Page

Adding an ACTE II (Adaptive Compliant Trailing Edge II) closeout summary to the ACTE II TechPort page

Towards single-molecule nanomechanical mass spectrometry

Mass spectrometry provides rapid and quantitative identification of protein species with relatively low sample consumption. The trend towards biological analysis at increasingly smaller scales, ultimately down to the volume of an individual cell, continues, and mass spectrometry with a sensitivity of a few to single molecules will be necessary. Nanoelectromechanical systems provide unparalleled mass sensitivity, which is now sufficient for the detection of individual molecular species in real time. Here, we report the first demonstration of mass spectrometry based on single biological molecule detection with a nanoelectromechanical system. In our nanoelectromechanical–mass spectrometry system, nanoparticles and protein species are introduced by electrospray injection from the fluid phase in ambient conditions into vacuum, and are subsequently delivered to the nanoelectromechanical system detector by hexapole ion optics. Precipitous frequency shifts, proportional to the mass, are recorded in real time as analytes adsorb, one by one, onto a phase-locked, ultrahigh-frequency nanoelectromechanical resonator. These first nanoelectromechanical system–mass spectrometry spectra, obtained with modest mass sensitivity from only several hundred mass adsorption events, presage the future capabilities of this approach. We also outline the substantial improvements that are feasible in the near term, some of which are unique to nanoelectromechanical system based-mass spectrometry

Time-resolved ferromagnetic resonance in epitaxial Fe1-xCox films

Magnetodynamics in epitaxial Fe1-xCox films on GaAs (100) are studied using time-resolved ferromagnetic resonance, in which the free precession of the magnetization after an impulsive excitation is measured using the polar Kerr effect. The sample is rotated with respect to the static and pulsed field directions, providing a complete mapping of the free energy surface and characteristic relaxation times. The magnetic response can be simulated with a simple coherent rotation model except in the immediate vicinity of switching fields. Bulk and surface anisotropies are identified, and unusual dynamics associated with the coexistence of cubic and uniaxial anisotropies are observed.Comment: PDF - 4 figure