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The presentation of a remote - but not proximal - distractor concurrent with target onset increases prosaccade reaction times (RT) (i.e., the remote distractor effect: RDE). The competitive integration model asserts that the RDE represents the time required to resolve the conflict for a common saccade threshold between target- and distractor-related saccade generating commands in the superior colliculus. To our knowledge however, no previous research has examined whether remote and proximal distractors differentially influence antisaccade RTs. This represents a notable question because antisaccades require decoupling of the spatial relations between stimulus and response (SR) and therefore provide a basis for determining whether the sensory- and/or motor-related features of a distractor influence response planning. Participants completed pro- and antisaccades in a target-only condition and conditions wherein the target was concurrently presented with a proximal or remote distractor. As expected, prosaccade RTs elicited a reliable RDE. In contrast, antisaccade RTs were increased independent of the distractor's spatial location and the magnitude of the effect was comparable across each distractor location. Thus, distractor-related antisaccade RT costs are not accounted for by a competitive integration between conflicting saccade generating commands. Instead, we propose that a visual distractor increases uncertainty related to the evocation of the response-selection rule necessary for decoupling SR relations.

Introduction The purpose of this study is to determine if delta waves, measured by magnetoencephalography (MEG), increase in adolescents due to a sports concussion. Methods Twenty‐four adolescents (age 14–17) completed pre‐ and postseason MRI and MEG scanning. MEG whole‐brain delta power was calculated for each subject and normalized by the subject's total power. In eight high school football players diagnosed with a concussion during the season (mean age = 15.8), preseason delta power was subtracted from their postseason scan. In eight high school football players without a concussion (mean age = 15.7), preseason delta power was subtracted from postseason delta power and in eight age‐matched noncontact controls (mean age = 15.9), baseline delta power was subtracted from a 4‐month follow‐up scan. ANOVA was used to compare the mean differences between preseason and postseason scans for the three groups of players, with pairwise comparisons based on Student's t‐test method. Results Players with concussions had significantly increased delta wave power at their postseason scans than nonconcussed players (p = .018) and controls (p = .027). Conclusion We demonstrate that a single concussion during the season in adolescent subjects can increase MEG measured delta frequency power at their postseason scan. This adds to the growing body of literature indicating increased delta power following a concussion. Graphical

INTRODUCTION Commercially available plasma p‐tau217 biomarker tests are not well studied in ethnically diverse samples. METHODS We evaluated associations between ALZPath plasma p‐tau217 and amyloid‐beta positron emission tomography (Aβ‐PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non‐Hispanic/Latino older adults. One‐ and two‐cutoff ranges were derived and evaluated to assess agreement with Aβ‐PET. RESULTS A total of 239 participants underwent blood draw and Aβ‐PET (age 70.8 ± 7.8, 55.2% female, education 15.6 ± 3.4 years, 48.9% Hispanic/Latino, 94.9% white). Plasma p‐tau217 showed excellent discrimination of Aβ‐PET positive and negative participants (visual read: AUC = 0.91 [0.87–0.95], p < 0.001; Centiloids quantification: AUC = 0.90 [0.86–0.94]). There was a greater percent agreement between low p‐tau217 and negative Aβ‐PET (95.8%) than high p‐tau217 and positive Aβ‐PET (86.3%). Analyses within ethnicity‐specific subgroups suggested similar p‐tau217 performance. DISCUSSION Plasma p‐tau217 (ALZPath) relates to brain Aβ in Hispanic/Latino and non‐Hispanic/Latino older adults. Independent validation and replication are necessary to establish reference ranges and inform appropriate contexts of use across ethno‐racially diverse populations. HIGHLIGHTS Plasma p‐tau217 (ALZPath) and Aβ‐PET were measured in Hispanic/Latino and non‐Hispanic/Latino older adults. Plasma p‐tau217 accurately discriminated Aβ‐PET positive and negative participants. Applying a two‐cutoff “intermediate” plasma p‐tau217 approach could reduce need for more invasive and costly testing. Plasma p‐tau217 associations with Aβ‐PET were strong within both Hispanic/Latino and non‐Hispanic/Latino groups.

INTRODUCTION Factors underlying discordant visual and quantitative amyloid beta–positron emission tomography (Aβ‐PET) results and their clinical implications are not well understood. METHODS Participants from the 1Florida Alzheimer's Disease Research Center (1FLADRC) underwent Aβ‐PET, blood draw, brain magnetic resonance imaging (MRI), and neuropsychological testing. We evaluated differences in demographics, apolipoprotein E (APOE) status, biomarkers, and cognition among older adults with concordant and discordant visual‐quantitative Aβ‐PET. Discordance was defined as positive visual read (V) of Aβ‐PET with below‐threshold Centiloid quantification (Q; CL <25; V+/Q–) or negative visual read with CL ≥25 (V–/Q+). RESULTS We studied 386 participants (mean age ± SD: 70.7 ± 7.8, 55.2% female, 44.6% Hispanic White). Compared to V+/Q–, V–/Q+ had a higher frequency of APOE ε4 carriers (40%). Black/African American participants were overrepresented in V–/Q+ (40.9%). Both discordant groups had higher plasma phosphorylated tau 217 (p‐tau217) and glial fibrillary acidic protein (GFAP) than V–/Q– but lower than V+/Q+. Discordant groups had greater gray matter volume and better cognitive performance than V+/Q+. DISCUSSION Discordant Aβ‐PET findings likely hold clinical significance and may reflect early stages of neuropathological progression. Highlights Groups with concordant/discordant visual‐quantitative amyloid beta–positron emission tomography (Aβ‐PET) results were compared. Visual–/quant+ were more likely than visual+/quant– to be apolipoprotein E (APOE) ε4 carriers and Black/African American. Discordant groups had higher plasma phosphorylated tau 217 (p‐tau217) and glial fibrillary acidic protein (GFAP) than concordant negative. Discordant groups had less atrophy and better cognition than concordant positive. Centiloid quantification should supplement visual reads in clinical settings.

Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes degeneration of Purkinje cells, and recent evidence points to degeneration of Betz cells in the motor cortex. The relation between functional activity of motor cortex and symptom severity during a hand-grip motor control in vivo has not yet been investigated. This study explored both functional changes in the sensorimotor cortex and cerebellar regions and structural alterations in the cerebellum for SCA6 patients as compared to age-matched healthy controls using a multimodal imaging approach (task-based fMRI, task-based functional connectivity, and free-water diffusion MRI). Further, we tested their relation with the severity of ataxia symptoms. SCA6 patients had reduced functional activity in the sensorimotor cortex, supplementary motor area (SMA), cerebellar vermis, and cerebellar lobules I-VI (corrected P  < 0.05). Reduced task-based functional connectivity between cortical motor regions (i.e., primary motor cortex and SMA) and cerebellar regions (i.e., vermis and lobules I–VI) was found in SCA6 (corrected P  < 0.05). SCA6 had elevated free-water values throughout the cerebellum as compared with controls (corrected P  < 0.05). Importantly, reduced functional activity in the sensorimotor cortex and SMA and increased free-water in the superior cerebellar peduncle and cerebellar lobule V were related to more severe symptoms in SCA6 (all pairs: R 2  ≥ 0.4 and corrected P  < 0.05). Current results demonstrate that impaired functional activity in sensorimotor cortex and SMA and elevated free-water of lobule V and superior cerebellar peduncle are both related to symptom severity, and may provide candidate biomarkers for SCA6.

INTRODUCTION Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid‐β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals. METHODS Diffusion free‐water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma‐/PET‐ (NC = 22, MCI = 60), plasma+/PET‐ (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross‐sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS Plasma+/PET‐ demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma‐/PET‐. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET‐. Composite brain FW correlated with plasma Aβ42/40 and p‐tau181. DISCUSSION FW imaging changes distinguish plasma Aβ42/40 positive and negative groups, independent of group differences in cognitive status, Aβ PET status, and other plasma biomarkers (i.e., t‐tau, p‐tau181, glial fibrillary acidic protein, neurofilament light). Highlights Plasma Aβ42/40 positivity is associated with brain microstructure decline. Plasma+/PET‐ demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET‐ demonstrated decreased FAt in 66 total GM and WM regions. Whole‐brain FW correlated with plasma Aβ42/40 and p‐tau181 measures. Plasma+/PET‐ demonstrated decreased cortical volume and thickness.

The saccade literature has consistently reported that the presentation of a distractor remote to a target increases reaction time (i.e., the remote distractor effect: RDE). As well, some studies have shown that a proximal distractor facilitates saccade reaction time. The lateral inhibition hypothesis attributes the aforementioned findings to the inhibition/facilitation of target selection mechanisms operating in the intermediate layers of the superior colliculus (SC). Although the impact of remote and proximal distractors has been extensively examined in the saccade literature, a paucity of work has examined whether such findings generalize to reaching responses, and to our knowledge, no work has directly contrasted reaching RTs for remote and proximal distractors. To that end, the present investigation had participants complete reaches in target only trials (i.e., TO) and when distractors were presented at “remote” (i.e., the opposite visual field) and “proximal” (i.e., the same visual field) locations along the same horizontal meridian as the target. As well, participants reached to the target’s veridical (i.e., propointing) and mirror-symmetrical (i.e., antipointing) location. The basis for contrasting pro- and antipointing was to determine whether the distractor’s visual- or motor-related activity influence reaching RTs. Results demonstrated that remote and proximal distractors, respectively, increased and decreased reaching RTs and the effect was consistent for pro- and antipointing. Accordingly, results evince that the RDE and the facilitatory effects of a proximal distractor are effector independent and provide behavioral support for the contention that the SC serves as a general target selection mechanism. As well, the comparable distractor-related effects for pro- and antipointing trials indicate that the visual properties of remote and proximal distractors respectively inhibit and facilitate target selection.

Dystonia musculorum deformans (early-onset generalized dystonia or DYT1 dystonia) is a neurological movement disorder that causes a loss of muscle control, unintentional movements, and disabling postures. The genetic hallmark includes a 3-bp deletion in the DYT1/TOR1A gene encoding the protein torsinA. The pathophysiology of dystonia is not well understood, which presents an obstacle to the development of effective symptomatic and disease-modifying therapies. Convergent evidence from human and animal studies has led to the conceptual view that dystonia represents a network disorder involving dysfunction of connected motor regions of the cortex, basal ganglia, and cerebellum. What is missing from this perspective is a deep understanding of how torsinA deficiency within specific cell types of these regions cause changes in dystonia-related phenotype and systems-level brain pathophysiology. Developing an in vivo perspective of brain pathophysiology related to cell-specific loss of torsinA is fundamental to our understanding of the neural substrates underlying dystonia and developing effective therapeutic strategies. In the present work, high-field (11.1 Tesla) multi-modal neuroimaging was performed in three mouse models of dystonia characterized by distinct cellular insults to the torsinA protein. Adaptations in brain function and microstructure were examined using functional and diffusion MRI, respectively. The results from these experiments yielded several important findings. First, mice carrying the corresponding gene mutation to human DYT1 dystonia or exhibiting the conditional knockout of torsinA within forebrain cholinergic and GABAergic cells exhibited widespread changes in the spatio-temporal correlation between low-frequency fluctuations in resting-state brain signal (i.e., functional connectivity). Second, the conditional knockout of torsinA from striatum-specific dopamine type-2 receptor expressing cells impaired blood-oxygen-level dependent signal activation and connectivity of sensorimotor regions, which correlated with motor performance deficits. Lastly, evidence from these studies establish the utility of advanced multi-compartment diffusion models as a potentially sensitive method to monitor microstructural adaptations in vivo.

Prosaccades are rapid eye movements with direct stimulus and response relations and are designed to bring the fovea onto a target or area of interest. In contrast, antisaccades require the inhibition of a prosaccade and the evocation of a saccade to a target’s mirror-symmetrical location. Previous work has shown that a remote (i.e., midline, contralateral) – but not proximal (i.e., ipsilateral) – task-irrelevant distractor relative to a visual target delays prosaccade reaction times (RT) (i.e., remote distractor effect: RDE). To my knowledge, however, no work has examined whether antisaccade RTs are similarly influenced by a RDE. Accordingly, I sought to determine whether planning costs for antisaccades are similarly dependent on the location-specific presentation of a distractor. In Chapter Two, I demonstrate increased antisaccade RTs independent of the spatial location of a distractor. Based on this result, I concluded that distractor-related antisaccade costs reflect the top-down evocation of explicit response-selection rules.

Atmospheric chemistry and transport of mercury play a key role in the global mercury cycle. However, there are still considerable knowledge gaps concerning the fate of mercury in the atmosphere. This is the second part of a model intercomparison study investigating the impact of atmospheric chemistry and emissions on mercury in the atmosphere. While the first study focused on ground-based observations of mercury concentration and deposition, here we investigate the vertical and interhemispheric distribution and speciation of mercury from the planetary boundary layer to the lower stratosphere. So far, there have been few model studies investigating the vertical distribution of mercury, mostly focusing on single aircraft campaigns. Here, we present a first comprehensive analysis based on various aircraft observations in Europe, North America, and on intercontinental flights. The investigated models proved to be able to reproduce the distribution of total and elemental mercury concentrations in the troposphere including interhemispheric trends. One key aspect of the study is the investigation of mercury oxidation in the troposphere. We found that different chemistry schemes were better at reproducing observed oxidized mercury patterns depending on altitude. High concentrations of oxidized mercury in the upper troposphere could be reproduced with oxidation by bromine while elevated concentrations in the lower troposphere were better reproduced by OH and ozone chemistry. However, the results were not always conclusive as the physical and chemical parameterizations in the chemistry transport models also proved to have a substantial impact on model results.