Knowledge about the configuration of an environment is used preferentially when navigating through an urban environment (Penn, 2003). However, it the locus of this effect is poorly understood. One possibility is that the local environment, such as the shape of an intersection, is sufficient to determine route choice in the context of the global configuration of an environment (Meilinger, Franz, & Bülthoff, in press; Meilinger, Knauff & Bülthoff, 2008). Two experiments were performed to investigate this hypothesis using two novel virtual environments, one with a simplistic configuration, and one with a more complicated configuration. In Experiment 1, peripheral vision was either available or constrained throughout a wayfinding task. A significant influence of global configuration information with minimal use of local configuration account was found. In Experiment 2, central vision was either limited to the local intersection or unconstrained. Again, a strong effect of configuration was found, with limited evidence for the use of local visual information. The results support a synergistic mechanism of wayfinding where the environmental configuration is used to inform existing knowledge about the environment.

Knowledge about the configuration of an environment is used preferentially when navigating through an urban environment (Penn, 2003). However, it the locus of this effect is poorly understood. One possibility is that the local environment, such as the shape of an intersection, is sufficient to determine route choice in the context of the global configuration of an environment (Meilinger, Franz, & Bülthoff, in press; Meilinger, Knauff & Bülthoff, 2008). Two experiments were performed to investigate this hypothesis using two novel virtual environments, one with a simplistic configuration, and one with a more complicated configuration. In Experiment 1, peripheral vision was either available or constrained throughout a wayfinding task. A significant influence of global configuration information with minimal use of local configuration account was found. In Experiment 2, central vision was either limited to the local intersection or unconstrained. Again, a strong effect of configuration was found, with limited evidence for the use of local visual information. The results support a synergistic mechanism of wayfinding where the environmental configuration is used to inform existing knowledge about the environment.

With the rapid advancements in technology, researchers are seeking new ways to incorporate modern high-tech solutions such as virtual reality into treatment paradigms for stress. The current experiment explores the beneficial effects of immersing an individual into virtual reality after a stressful encounter. I examined the potential restorative effects of three unique immersive virtual reality environments by inducing stress and negative affect in sixty-nine participants and then randomly assigning them to freely explore one of three environments (a virtual nature setting, a virtual urban cityscape, or a neutral environment composed of solid geometric shapes) for ten minutes. Participants who explored the nature environment were found to have significantly improved affect (as measured by a standardized questionnaire), and significantly lower stress levels (as measured by self-report and skin-conductance levels) compared to those who explored the urban and geometric environments. The results suggest that virtual nature has restorative properties similar to real nature, and that simply immersing participants into a virtual nature setting can reduce stress. These results also suggest that the content of the virtual reality experience (i.e., whether it contains nature) is important in promoting restoration, and that in the absence of nature, stress levels remain unchanged.

The ability to correct balance disturbances is essential for maintaining upright stability. Recent literature highlights a potentially important role for the cerebral cortex in controlling compensatory balance reactions. The objective of this research was to provide a more detailed understanding of the specific neurophysiologic events occurring at the cortex following balance disturbances. More specifically, the focus was to determine whether the N1, a cortical potential evoked during balance control, and the error-related negativity (ERN), a cortical potential measured in response to errors during cognitive tasks, have similar cortical representation, revealing a similar link to an error detection mechanism. It was hypothesized that the N1 and ERN would have the same generator located in the anterior cingulate cortex (ACC). Fourteen healthy young adults participated in a balance task (evoked N1) and a flanker task (evoked ERN). Temporally unpredictable perturbations to standing balance were achieved using a lean and release cable system. Electromyography and centre of pressure were measured during the balance task. Reaction times and error rates were measured during the flanker task. Electroencephalography was recorded during both tasks. Source localization was performed in CURRY 6 using a single fixed coherent dipole model to determine the neural generator of the N1 and ERN. The results revealed that the locations of the N1 and ERN dipoles were different. The mean (n=9) distance between N1 and ERN dipoles was 25.46 ± 8.88 mm. The mean Talairach coordinates for the ERN dipole were (6.47 ± 3.08, -4.41 ± 13.15, 41.17 ± 11.63) mm, corresponding to the cingulate gyrus (Brodmann area 24). This represents the ACC, supporting results from previous literature. The mean Talairach coordinates for the N1 dipole were (5.74 ± 3.77, -11.81 ± 10.84, 53.73 ± 7.30) mm, corresponding to the medial frontal gyrus (Brodmann area 6). This is the first work to localize the source of the N1. It is speculated that the generator of the N1 is the supplementary motor area and that it represents the generation of a contingency motor plan to shape the later phases of the compensatory balance response based on sensory feedback from the perturbation.

With the rapid advancements in technology, researchers are seeking new ways to incorporate modern high-tech solutions such as virtual reality into treatment paradigms for stress. The current experiment explores the beneficial effects of immersing an individual into virtual reality after a stressful encounter. I examined the potential restorative effects of three unique immersive virtual reality environments by inducing stress and negative affect in sixty-nine participants and then randomly assigning them to freely explore one of three environments (a virtual nature setting, a virtual urban cityscape, or a neutral environment composed of solid geometric shapes) for ten minutes. Participants who explored the nature environment were found to have significantly improved affect (as measured by a standardized questionnaire), and significantly lower stress levels (as measured by self-report and skin-conductance levels) compared to those who explored the urban and geometric environments. The results suggest that virtual nature has restorative properties similar to real nature, and that simply immersing participants into a virtual nature setting can reduce stress. These results also suggest that the content of the virtual reality experience (i.e., whether it contains nature) is important in promoting restoration, and that in the absence of nature, stress levels remain unchanged.

The ability to correct balance disturbances is essential for maintaining upright stability. Recent literature highlights a potentially important role for the cerebral cortex in controlling compensatory balance reactions. The objective of this research was to provide a more detailed understanding of the specific neurophysiologic events occurring at the cortex following balance disturbances. More specifically, the focus was to determine whether the N1, a cortical potential evoked during balance control, and the error-related negativity (ERN), a cortical potential measured in response to errors during cognitive tasks, have similar cortical representation, revealing a similar link to an error detection mechanism. It was hypothesized that the N1 and ERN would have the same generator located in the anterior cingulate cortex (ACC). Fourteen healthy young adults participated in a balance task (evoked N1) and a flanker task (evoked ERN). Temporally unpredictable perturbations to standing balance were achieved using a lean and release cable system. Electromyography and centre of pressure were measured during the balance task. Reaction times and error rates were measured during the flanker task. Electroencephalography was recorded during both tasks. Source localization was performed in CURRY 6 using a single fixed coherent dipole model to determine the neural generator of the N1 and ERN. The results revealed that the locations of the N1 and ERN dipoles were different. The mean (n=9) distance between N1 and ERN dipoles was 25.46 ± 8.88 mm. The mean Talairach coordinates for the ERN dipole were (6.47 ± 3.08, -4.41 ± 13.15, 41.17 ± 11.63) mm, corresponding to the cingulate gyrus (Brodmann area 24). This represents the ACC, supporting results from previous literature. The mean Talairach coordinates for the N1 dipole were (5.74 ± 3.77, -11.81 ± 10.84, 53.73 ± 7.30) mm, corresponding to the medial frontal gyrus (Brodmann area 6). This is the first work to localize the source of the N1. It is speculated that the generator of the N1 is the supplementary motor area and that it represents the generation of a contingency motor plan to shape the later phases of the compensatory balance response based on sensory feedback from the perturbation.

Amyloid beta (ABeta) and tau protein are both implicated in memory impairment in early Alzheimer’s disease, but whether and how they interact to cause synaptic dysfunction are unknown. Consequently, I firstly investigated whether tau protein is required for the robust phenomenon of ABeta-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. I demonstrate that the absence of tau prevents the ABeta-induced impairment of LTP; moreover, a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks both an ABeta-induced increase in tau phosphorylation and the ABeta-induced LTP impairment. Thus, tau protein, likely in its phosphorylated form, is required for ABeta to impair LTP. Secondly, I investigated the underlying mechanisms for this ABeta-induced impairment and find that ABeta changes the balance between the two major types of glutamate receptors involved in plasticity processes, with a specific effect on GluN2B subunit-containing NMDA receptors. Since the distribution of these receptors is asymmetric between the left and right mouse hippocampus, I accessed these different types of synapses optogenetically and found that only the GluN2B-rich synapses receiving left CA3 input show ABeta-induced changes in the balance of glutamate receptors, suggesting an asymmetry in synaptic vulnerability to ABeta. Moreover, there was a left-right difference in tetanus-induced LTP and therefore, thirdly, I investigated whether mice have a hemispheric dissociation in memory processing using acute optogenetic silencing of left or right CA3 during hippocampus-dependent memory tasks. Unilateral silencing of either the left or the right CA3 caused a deficit in short-term memory, but only left CA3 silencing impaired performance on a spatial long-term memory task. Together, these results suggest that memory may be routed via distinct left-right pathways within the mouse hippocampus, and that neural pathways subserving distinct functions may also be differentially vulnerable to pathological changes at the synaptic level.

<p>A C. elegans model of nicotine use and aversion resistance following chronic low-dose nicotine pretreatment. Model was then applied to various receptor knockouts  (acr-5, acr-15, acr-16, dop-1, and dop-2) to determine the role of these receptors in aversion resistance. </p>

<p dir="ltr">Frontloading is an alcohol drinking pattern where intake is skewed toward the onset of access. The goal of the current study was to identify brain regions involved in frontloading using whole brain imaging. 63 C57Bl/6J (32 female and 31 male) mice underwent 8 days of binge drinking using drinking-in-the-dark (DID). Three hours into the dark cycle, mice received 20% (v/v) alcohol or water for two hours on days 1-7. Intake was measured in 1-minute bins using volumetric sippers, which facilitated analyses of drinking patterns. Mice were perfused 80 minutes into the day 8 DID session and brains were extracted and processed for iDISCO clearing and c-fos immunohistochemistry. For brain network analyses, day 8 drinking patterns were used to characterize mice as frontloaders or non-frontloaders using a change-point analysis described in our recent ACER publication (Ardinger et al., 2022). Groups were female frontloaders (n = 20), female non-frontloaders (n = 2), male frontloaders (n = 13) and male non-frontloaders (n = 8). There were no differences in total alcohol intake as a function of frontloading status. Water drinkers had an n of 10 for each sex. As only two female mice were characterized as non-frontloaders, it was not possible to construct a functional correlation network for this group. Following light sheet imaging, ClearMap2.1 was used to register brains to the Allen Brain Atlas and detect fos+ cells. Functional correlation matrices were calculated for each group from log₁₀ c-fos values. Euclidean distances were calculated from these R values and hierarchical clustering was used to determine modules (highly connected groups of brain regions) at a tree-cut height of 50%. In males, alcohol access decreased modularity (3 modules in both frontloaders and non-frontloaders) as compared to water drinkers (7 modules). In females, an opposite effect was observed. Alcohol access (9 modules) increased modularity as compared to water drinkers (5 modules). These results suggest sex differences in how alcohol consumption reorganizes the functional architecture of networks. Next, key brain regions in each network were identified. Connector hubs, which primarily facilitate communication between modules, and provincial hubs, which facilitate communication within modules, were of specific interest for their important and differing roles. In males, 4 connector hubs and 17 provincial hubs were uniquely identified in frontloaders (i.e., were brain regions that did not have this status in male non-frontloaders or water drinkers). These represented a group of hindbrain regions (e.g., locus coeruleus and the pontine gray) connected to striatal/cortical regions (e.g., cortical amygdalar area) by the paraventricular nucleus of the thalamus. In females, 16 connector and 17 provincial hubs were uniquely identified which were distributed across 8 of the 9 modules in the female alcohol drinker network. Only one brain region (the nucleus raphe pontis) was a connector hub in both sexes, suggesting that frontloading in males and females may be driven by different brain regions. In conclusion, alcohol consumption led to fewer, but more densely connected, groups of brain regions in males but not females, and recruited different hub brain regions between the sexes. These results suggest target brain regions for future studies to try to manipulate frontloading behavior and more broadly contribute to the literature on alcohol’s effect on neural networks.</p>

<p dir="ltr">Previous research shows that the prevalence rates for alcohol use disorder, opioid use disorder, and chronic pain are high worldwide. Additional work has demonstrated that the most used pain medications are potentially addictive and not suitable for chronic use. Recent research suggests that inhibiting adenylyl cyclase type 1 (AC1) may be an alternative, non-addictive, method for reducing pain. The purpose of this study was to explore the effects of a novel AC1 inhibitor (CMPD84) on pain threshold and alcohol reward-related behavior in high-alcohol preferring male and female mice (HAP). No research to date has investigated the effects of AC1 inhibition on pain threshold and alcohol-induced conditioned place preference (CPP) in HAP mice, making this the first study to do so. Two manual von Frey experiments were run to explore the effects of CMPD84 (compared to alcohol and morphine) on pain threshold. Three CPP experiments were run to assess the effects of CMPD84 on the expression and acquisition of alcohol-induced CPP. Brain samples were taken from the NAc shell and vlPAG to assess levels of PKCε after the pain threshold experiments and the acquisition CPP experiment. PKCε has previously been shown to be linked to alcohol reward-behavior and pain relief. Results show that CMPD84 was more efficacious in increasing pain threshold in HAP mice compared to morphine and alcohol. CMPD84 also reduced the acquisition and expression of alcohol-induced CPP. AC1 inhibition reduced levels of PKCε in the brain, which matched behavioral results that reduced the expression and acquisition of alcohol-induced CPP, as well as increased pain threshold. These results suggest that PKCε may be linked to AC1 inhibition, pain threshold, and alcohol reward-related behaviors. </p>