Browsing by Subject "LRP"
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Item Open Access Improvement in visual search with practice: mapping learning-related changes in neurocognitive stages of processing.(J Neurosci, 2015-04-01) Clark, Kait; Appelbaum, L Gregory; van den Berg, Berry; Mitroff, Stephen R; Woldorff, Marty GPractice can improve performance on visual search tasks; the neural mechanisms underlying such improvements, however, are not clear. Response time typically shortens with practice, but which components of the stimulus-response processing chain facilitate this behavioral change? Improved search performance could result from enhancements in various cognitive processing stages, including (1) sensory processing, (2) attentional allocation, (3) target discrimination, (4) motor-response preparation, and/or (5) response execution. We measured event-related potentials (ERPs) as human participants completed a five-day visual-search protocol in which they reported the orientation of a color popout target within an array of ellipses. We assessed changes in behavioral performance and in ERP components associated with various stages of processing. After practice, response time decreased in all participants (while accuracy remained consistent), and electrophysiological measures revealed modulation of several ERP components. First, amplitudes of the early sensory-evoked N1 component at 150 ms increased bilaterally, indicating enhanced visual sensory processing of the array. Second, the negative-polarity posterior-contralateral component (N2pc, 170-250 ms) was earlier and larger, demonstrating enhanced attentional orienting. Third, the amplitude of the sustained posterior contralateral negativity component (SPCN, 300-400 ms) decreased, indicating facilitated target discrimination. Finally, faster motor-response preparation and execution were observed after practice, as indicated by latency changes in both the stimulus-locked and response-locked lateralized readiness potentials (LRPs). These electrophysiological results delineate the functional plasticity in key mechanisms underlying visual search with high temporal resolution and illustrate how practice influences various cognitive and neural processing stages leading to enhanced behavioral performance.Item Open Access Incorporation of CpG Oligodeoxynucleotides into α2-Macroglobulin: Development of a Novel Vaccine Adjuvant Delivery Mechanism(2007-05-02T14:53:43Z) Anderson, Ryan BergerBacterial DNA is immunostimulatory, and the motifs responsible for this activity are unmethylated CpG dinucleotides. Following cellular uptake, CpG-containing oligodeoxynucleotides (CpG ODN) are trafficked to the endosome where they bind Toll-like receptor 9 (TLR9) to initiate a signaling cascade that culminates in the release of numerous pro-inflammatory cytokines. Because of their immunostimulatory properties, CpG ODN are being clinically evaluated as treatments and vaccine adjuvants for infectious diseases, cancer, and allergic disorders. α2-Macroglobulin (α2M) is a human plasma protein that binds and modulates the activity of a variety of cytokines, growth factors, enzymes, and antigens. Upon proteolytic activation, α2M is converted to its receptor recognized form, α2M*, and rapidly binds to and is internalized by immune competent cells expressing the α2M* endocytic receptor, LRP, and is then trafficked to the endosome. Based on these interactions, α2M seems to play an important role at sites of infection and inflammation by controlling the level of proteinase activity, modulating cytokine signals, and enhancing antigen processing for the adaptive immune response. Here, we report the first evidence that α2M* binds and forms stable complexes with nucleic acids. We have characterized the mechanisms and stoichiometry of this interaction, examined the pH and temperature stability of these complexes, and identified structural variables in the nucleic acids, namely length, base composition, and chemical modifications, that affect the nature of this interaction. We hypothesized that CpG ODN incorporation into α2M* may alter their immunostimulatory properties. Murine macrophages (MΦs) treated with α2M*-ODN complexes respond more rapidly and produce a greater cytokine response than those treated with free CpG ODN alone. Treating human PBMCs with α2M*-ODN complexes likewise demonstrated their enhanced ability to elicit immune responses. This was due to more rapid uptake and CpG ODN protection from degradation by extracellular nucleases. Co-incorporation of both protein ligands and CpG ODN into α2M* yields ternary complexes; these may permit the simultaneous delivery of both protein antigens and adjuvants to immune competent cells, potentially greatly enhancing the adaptive immune response and protective immunity. Based on the findings that incorporation into α2M* confers enhanced immunostimulatory activity of CpG ODN, this technology may be exploited to improve CpG ODN-based therapeutics by increasing efficacy, minimizing side effects, reducing dosing requirements, and reducing cost.Item Open Access The neural dynamics of stimulus and response conflict processing as a function of response complexity and task demands.(Neuropsychologia, 2016-04) Donohue, Sarah E; Appelbaum, Lawrence G; McKay, Cameron C; Woldorff, Marty GBoth stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally-distributed negativity at ~200 ms that was only present in the Flanker spatial-conflict task. At longer latencies, the classic fronto-central incongruency-related negativity 'N(inc)' was observed for all conditions, but was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor-response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict-related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related N(inc), indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options.