Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition.

Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aß42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aß when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity.

Pollinator foraging tactics have divergent consequences for the mating system of a tropical plant.

Resolving the consequences of pollinator foraging behaviour for plant mating systems is a fundamental challenge in evolutionary ecology. Pollinators may adopt particular foraging tactics: complete trapline foraging (repeated movements along a fixed route), sample-and-shift trapline foraging (a variable route that incorporates information from previous experiences) and territorial foraging (stochastic movements within a restricted area). Studies that integrate these pollinator foraging tactics with plant mating systems are generally lacking. We investigate the consequences of particular pollinator foraging tactics for Heliconia tortuosa. We combine parentage and sibship inference analysis with simulation modelling to: estimate mating system parameters; infer the foraging tactic adopted by the pollinators; and quantify the impact of pollinator foraging tactics on mating system parameters. We found high outcrossing rates, ubiquitous multiple paternity and a pronounced departure from near-neighbour mating. We also found that plants repeatedly receive pollen from a series of particular donors. We infer that the pollinators primarily adopt complete trapline foraging and occasionally engage in sample-and-shift trapline foraging. This enhances multiple paternity without a substantial increase in near-neighbour mating. The particular pollinator foraging tactics have divergent consequences for multiple paternity and near-neighbour mating. Thus, pollinator foraging behaviour is an important driver of the ecology and evolution of plant mating systems.

In vivo tractography of human locus coeruleus-relation to 7T resting state fMRI, psychological measures and single subject validity.

The locus coeruleus (LC) in the brainstem as the main regulator of brain noradrenaline gains increasing attention because of its involvement in neurologic and psychiatric diseases and its relevance in general to brain function. In this study, we created a structural connectome of the LC nerve fibers based on in vivo MRI tractography to gain an understanding into LC connectivity and its impact on LC-related psychological measures. We combined our structural results with ultra-high field resting-state functional MRI to learn about the relationship between in vivo LC structural and functional connections. Importantly, we reveal that LC brain fibers are strongly associated with psychological measures of anxiety and alertness indicating that LC-noradrenergic connectivity may have an important role on brain function. Lastly, since we analyzed all our data in subject-specific space, we point out the potential of structural LC connectivity to reveal individual characteristics of LC-noradrenergic function on the single-subject level.

Bee diversity decreases rapidly with time since harvest in intensively managed conifer forests.

Despite widespread concerns about the anthropogenic drivers of global pollinator declines, little information is available about the impacts of land management practices on wild bees outside of agricultural systems, including in forests managed intensively for wood production. We assessed changes in wild bee communities with time since harvest in 60 intensively managed Douglas-fir (Pseudotsuga menziesii) stands across a gradient in stand ages spanning a typical harvest rotation. We measured bee abundance, species richness, and alpha and beta diversity, as well as habitat characteristics (i.e., floral resources, nesting substrates, understory vegetation, and early seral forest in the surrounding landscape) during the spring and summer of 2018 and 2019. We found that bee abundance and species richness declined rapidly with stand age, decreasing by 61% and 48%, respectively, for every 5 years since timber harvest. Asymptotic estimates of Shannon and Simpson diversity were highest in stands 6-10 years post-harvest and lowest after the forest canopy had closed, ~11 years post-harvest. Bee communities in older stands were nested subsets of bee communities found in younger stands, indicating that changes were due to species loss rather than turnover as the stands aged. Bee abundance-but not species richness-was positively associated with floral resource density, and neither metric was associated with floral richness. The amount of early seral forest in the surrounding landscape seemed to enhance bee species richness in older, closed-canopy stands, but otherwise had little effect. Changes in the relative abundance of bee species did not relate to bee functional characteristics such as sociality, diet breadth, or nesting substrate. Our study demonstrates that Douglas-fir plantations develop diverse communities of wild bees shortly after harvest, but those communities erode rapidly over time as forest canopies close. Therefore, stand-scale management activities that prolong the precanopy closure period and enhance floral resources during the initial stage of stand regeneration will provide the greatest opportunity to enhance bee diversity in landscapes dominated by intensively managed conifer forests.

Plant-hummingbird pollination networks exhibit limited rewiring after experimental removal of a locally abundant plant species.

Mutualistic relationships, such as those between plants and pollinators, may be vulnerable to the local extinctions predicted under global environmental change. However, network theory predicts that plant-pollinator networks can withstand species loss if pollinators switch to alternative floral resources (rewiring). Whether rewiring occurs following species loss in natural communities is poorly known because replicated species exclusions are difficult to implement at appropriate spatial scales. We experimentally removed a hummingbird-pollinated plant, Heliconia tortuosa, from within tropical forest fragments to investigate how hummingbirds respond to temporary loss of an abundant resource. Under the rewiring hypothesis, we expected that behavioural flexibility would allow hummingbirds to use alternative resources, leading to decreased ecological specialization and reorganization of the network structure (i.e. pairwise interactions). Alternatively, morphological or behavioural constraints-such as trait-matching or interspecific competition-might limit the extent to which hummingbirds alter their foraging behaviour. We employed a replicated Before-After-Control-Impact experimental design and quantified plant-hummingbird interactions using two parallel sampling methods: pollen collected from individual hummingbirds ('pollen networks', created from >300 pollen samples) and observations of hummingbirds visiting focal plants ('camera networks', created from >19,000 observation hours). To assess the extent of rewiring, we quantified ecological specialization at the individual, species and network levels and examined interaction turnover (i.e. gain/loss of pairwise interactions). H. tortuosa removal caused some reorganization of pairwise interactions but did not prompt large changes in specialization, despite the large magnitude of our manipulation (on average, >100 inflorescences removed in exclusion areas of >1 ha). Although some individual hummingbirds sampled through time showed modest increases in niche breadth following Heliconia removal (relative to birds that did not experience resource loss), these changes were not reflected in species- and network-level specialization metrics. Our results suggest that, at least over short time-scales, animals may not necessarily shift to alternative resources after losing an abundant food resource-even in species thought to be highly opportunistic foragers, such as hummingbirds. Given that rewiring contributes to theoretical predictions of network stability, future studies should investigate why pollinators might not expand their diets after a local resource extinction.

Fragmentation effects on an endangered species across a gradient from the interior to edge of its range.

Understanding how habitat fragmentation affects individual species is complicated by challenges associated with quantifying species-specific habitat and spatial variability in fragmentation effects within a species' range. We aggregated a 29-year breeding survey data set for the endangered marbled murrelet (Brachyramphus marmoratus) from >42,000 forest sites throughout the Pacific Northwest (Oregon, Washington, and northern California) of the United States. We built a species distribution model (SDM) in which occupied sites were linked with Landsat imagery to quantify murrelet-specific habitat and then used occupancy models to test the hypotheses that fragmentation negatively affects murrelet breeding distribution and that these effects are amplified with distance from the marine foraging habitat toward the edge of the species' nesting range. Murrelet habitat declined in the Pacific Northwest by 20% since 1988, whereas the proportion of habitat comprising edges increased by 17%, indicating increased fragmentation. Furthermore, fragmentation of murrelet habitat at landscape scales (within 2 km of survey stations) negatively affected occupancy of potential breeding sites, and these effects were amplified near the range edge. On the coast, the odds of occupancy decreased by 37% (95% confidence interval [CI] -54 to 12) for each 10% increase in edge habitat (i.e., fragmentation), but at the range edge (88 km inland) these odds decreased by 99% (95% CI 98 to 99). Conversely, odds of murrelet occupancy increased by 31% (95% CI 14 to 52) for each 10% increase in local edge habitat (within 100 m of survey stations). Avoidance of fragmentation at broad scales but use of locally fragmented habitat with reduced quality may help explain the lack of murrelet population recovery. Further, our results emphasize that fragmentation effects can be nuanced, scale dependent, and geographically variable. Awareness of these nuances is critical for developing landscape-level conservation strategies for species experiencing broad-scale habitat loss and fragmentation.

Efectos de la fragmentación sobre las especies en peligro a lo largo de un gradiente desde el interior hasta el borde de su distribución Resumen Es complicado entender el efecto de la fragmentación del hábitat sobre las especies individuales debido a los retos asociados con la cuantificación de hábitats específicos por especie y la variabilidad espacial de los efectos de la fragmentación dentro de la distribución de la especie. Combinamos los datos de un censo reproductivo realizado durante 29 años para el mérgulo jaspeado (Brachyramphus marmoratus) de >42,000 sitios boscosos a lo largo del noroeste del Pacífico (Oregón, Washington, y el norte de California, EE. UU.). Construimos un modelo de distribución de especie (MDE) en el cual los sitios ocupados estuvieron vinculados con imágenes de Landsat para cuantificar el hábitat específico del mérgulo y después usamos los modelos de ocupación para comprobar la hipótesis de que la fragmentación afecta negativamente la distribución reproductiva de la especie y que estos efectos se amplifican con la distancia entre el hábitat de forrajeo marino y el borde de la distribución de anidación de la especie. El hábitat del mérgulo declinó en la zona en un 20% a partir de 1988, mientras que la proporción de hábitat que comprende bordes incrementó en un 17%, lo que indica un aumento en la fragmentación. Además, la fragmentación del hábitat del mérgulo a escala de paisaje (a de 2 km de las estaciones de censo) afectó negativamente a la ocupación de sitios potenciales de reproducción y estos efectos se amplificaron cerca del borde de la distribución. La probabilidad de ocupación disminuyó en un 37% (95% IC -54 a 12) por cada 10% de incremento en el hábitat de borde (es decir, fragmentación) en la costa, pero en el borde de la distribución (88 km tierra adentro), esta probabilidad disminuyó en un 99% (95% IC 98 a 99). De forma contraria, la probabilidad de ocupación incrementó en un 31% (95% IC 14 a 52) por cada 10% de incremento en el hábitat de borde local (a 100 m de las estaciones de censo). La evasión de la fragmentación a gran escala y el uso de hábitats con calidad reducida y fragmentados a nivel local podría explicar la falta de recuperación poblacional del mérgulo. Más allá, nuestros resultados resaltan que los efectos de la fragmentación pueden estar matizados, depender de la escala y tener variación geográfica. Es importante tener conciencia de estos matices para desarrollar estrategias de conservación a nivel paisaje para las especies que experimentan fragmentación y pérdida del hábitat a gran escala.

Global forest loss disproportionately erodes biodiversity in intact landscapes.

Global biodiversity loss is a critical environmental crisis, yet the lack of spatial data on biodiversity threats has hindered conservation strategies. Theory predicts that abrupt biodiversity declines are most likely to occur when habitat availability is reduced to very low levels in the landscape (10-30%). Alternatively, recent evidence indicates that biodiversity is best conserved by minimizing human intrusion into intact and relatively unfragmented landscapes. Here we use recently available forest loss data to test deforestation effects on International Union for Conservation of Nature Red List categories of extinction risk for 19,432 vertebrate species worldwide. As expected, deforestation substantially increased the odds of a species being listed as threatened, undergoing recent upgrading to a higher threat category and exhibiting declining populations. More importantly, we show that these risks were disproportionately high in relatively intact landscapes; even minimal deforestation has had severe consequences for vertebrate biodiversity. We found little support for the alternative hypothesis that forest loss is most detrimental in already fragmented landscapes. Spatial analysis revealed high-risk hot spots in Borneo, the central Amazon and the Congo Basin. In these regions, our model predicts that 121-219 species will become threatened under current rates of forest loss over the next 30 years. Given that only 17.9% of these high-risk areas are formally protected and only 8.9% have strict protection, new large-scale conservation efforts to protect intact forests are necessary to slow deforestation rates and to avert a new wave of global extinctions.

Artificial intelligence for diagnostic and prognostic neuroimaging in dementia: A systematic review.

INTRODUCTION: Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. METHODS: We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases. RESULTS: A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort. DISCUSSION: The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice. HIGHLIGHTS: There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias.

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

Locus coeruleus catecholamines link neuroticism and vulnerability to tau pathology in aging.

Higher neuroticism is a risk factor for Alzheimer's disease (AD), and is implicated in disordered stress responses. The locus coeruleus (LC)-catecholamine system is activated during perceived threat and is a centerpiece of developing models of the pathophysiology of AD, as it is the first brain region to develop abnormal tau. We examined relationships among the "Big 5" personality traits, LC catecholamine synthesis capacity measured with [18F]Fluoro-m-tyrosine PET, and tau burden measured with [18F]Flortaucipir PET in cognitively normal older adults (n = 47). ß-amyloid (Aß) status was determined using [11C]Pittsburgh compound B PET (n = 14 Aß positive). Lower LC catecholamine synthesis capacity was associated with higher neuroticism, more depressive symptoms as measured by the Geriatric Depression Scale, and higher amygdala tau-PET binding. Exploratory analyses with other personality traits revealed that low trait conscientiousness was also related to both lower LC catecholamine synthesis capacity, and more depressive symptoms. A significant indirect path linked both high neuroticism and low conscientiousness to greater amygdala tau burden via their mutual association with low LC catecholamine synthesis capacity. Together, these findings reveal LC catecholamine synthesis capacity to be a promising marker of affective health and pathology burden in aging, and identifies candidate neurobiological mechanisms for the effect of personality on increased vulnerability to dementia.

Elevated inbreeding in Heliconia tortuosa is determined by tropical forest stand age, isolation and loss of hummingbird functional diversity.

Forest conversion and habitat loss are major threats to biological diversity. Forest regeneration can mitigate the negative effects of old-growth forest loss on species diversity, but less is known about the extent to which forest loss reduces genetic diversity in remnant populations and whether secondary forests play a role in the maintenance of genetic diversity. We quantified genetic diversity in a tropical hummingbird-pollinated understorey herb, Heliconia tortuosa, across a landscape mosaic of primary and secondary forest regrowth. Using microsatellite genotypes from >850 adult and juvenile plants within 33 forest patches and extensive bird surveys, we examined the effect of contemporary and historical landscape features including forest age (primary vs. secondary forest), stand isolation and pollinator assemblages on genetic diversity and levels of inbreeding in H. tortuosa. We found that inbreeding was up to three times higher in secondary forest, and this effect was amplified with reductions in primary forest in the surrounding landscape through reduced observed heterozygosity in isolated fragments. Inbreeding in forest patches was negatively correlated with the local frequency of specialist long-distance foraging traplining hummingbirds. Traplining hummingbirds therefore appear to facilitate mating among unrelated plants-an inference we tested using empirically parameterized simulations. Higher levels of inbreeding in H. tortuosa are therefore associated with reduced functional diversity of hummingbirds in secondary forests and forest patches isolated from primary forests. Our findings suggest a cryptic consequence of primary forest loss and secondary forest regeneration through the disruption of mutualistic interactions resulting in the erosion of genetic diversity in a common understorey plant.

Forest microclimate and composition mediate long-term trends of breeding bird populations.

Climate change is contributing to biodiversity redistributions and species declines. However, cooler microclimate conditions provided by old-growth forest structures compared with surrounding open or younger forests have been hypothesized to provide thermal refugia for species that are sensitive to climate warming and dampen the negative effects of warming on population trends of animals (i.e., the microclimate buffering hypothesis). In addition to thermal refugia, the compositional and structural diversity of old-growth forest vegetation itself may provide resources to species that are less available in forests with simpler structure (i.e., the insurance hypothesis). We used 8 years of breeding bird abundance data from a forested watershed, accompanied with sub-canopy temperature data, and ground- and LiDAR-based vegetation data to test these hypotheses and identify factors influencing bird population changes from 2011 to 2018. After accounting for imperfect detection, we found that for 5 of 20 bird species analyzed, abundance trends tended to be less negative or neutral at sites with cooler microclimates, which supports the microclimate buffering hypothesis. Negative effects of warming on two species were also reduced in locations with greater forest compositional diversity supporting the insurance hypothesis. We provide the first empirical evidence that complex forest structure and vegetation diversity confer microclimatic advantages to some animal populations in the face of climate change. Conservation of old-growth forests, or their characteristics in managed forests, could help slow the negative effects of climate warming on some breeding bird populations via microclimate buffering and possibly insurance effects.

Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson's disease.

Previous studies have reported substantial involvement of the noradrenergic system in Parkinson's disease. Neuromelanin-sensitive MRI sequences and PET tracers have become available to visualize the cell bodies in the locus coeruleus and the density of noradrenergic terminal transporters. Combining these methods, we investigated the relationship of neurodegeneration in these distinct compartments in Parkinson's disease. We examined 93 subjects (40 healthy controls and 53 Parkinson's disease patients) with neuromelanin-sensitive turbo spin-echo MRI and calculated locus coeruleus-to-pons signal contrasts. Voxels with the highest intensities were extracted from published locus coeruleus coordinates transformed to individual MRI. To also investigate a potential spatial pattern of locus coeruleus degeneration, we extracted the highest signal intensities from the rostral, middle, and caudal third of the locus coeruleus. Additionally, a study-specific probabilistic map of the locus coeruleus was created and used to extract mean MRI contrast from the entire locus coeruleus and each rostro-caudal subdivision. Locus coeruleus volumes were measured using manual segmentations. A subset of 73 subjects had 11C-MeNER PET to determine noradrenaline transporter density, and distribution volume ratios of noradrenaline transporter-rich regions were computed. Patients with Parkinson's disease showed reduced locus coeruleus MRI contrast independently of the selected method (voxel approaches: P < 0.0001, P < 0.001; probabilistic map: P < 0.05), specifically on the clinically-defined most affected side (P < 0.05), and reduced locus coeruleus volume (P < 0.0001). Reduced MRI contrast was confined to the middle and caudal locus coeruleus (voxel approach, rostral: P = 0.48, middle: P < 0.0001, and caudal: P < 0.05; probabilistic map, rostral: P = 0.90, middle: P < 0.01, and caudal: P < 0.05). The noradrenaline transporter density was lower in patients with Parkinson's diseasein all examined regions (group effect P < 0.0001). No significant correlation was observed between locus coeruleus MRI contrast and noradrenaline transporter density. In contrast, the individual ratios of noradrenaline transporter density and locus coeruleus MRI contrast were lower in Parkinson's disease patients in all examined regions (group effect P < 0.001). Our multimodal imaging approach revealed pronounced noradrenergic terminal loss relative to cellular locus coeruleus degeneration in Parkinson's disease; the latter followed a distinct spatial pattern with the middle-caudal portion being more affected than the rostral part. The data shed first light on the interaction between the axonal and cell body compartments and their differential susceptibility to neurodegeneration in Parkinson's disease, which may eventually direct research towards potential novel treatment approaches.

Impacts of the Northwest Forest Plan on forest composition and bird populations.

The Northwest Forest Plan (NWFP) initiated one of the most sweeping changes to forest management in the world, affecting 10 million hectares of federal land. The NWFP is a science-based plan incorporating monitoring and adaptive management and provides a unique opportunity to evaluate the influence of policy. We used >25 years of region-wide bird surveys, forest data, and land-ownership maps to test this policy's effect on biodiversity. Clearcutting decreased rapidly, and we expected populations of older-forest-associated birds to stabilize on federal land, but to continue declining on private industrial lands where clearcutting continued. In contrast, we expected declines in early-seral-associated species on federal land because of reduced anthropogenic disturbance since the NWFP. Bayesian hierarchical models revealed that bird species' population trends tracked changes in forest composition. However, against our expectations, declines of birds associated with older forests accelerated. These declines are partly explained by losses of older forests due to fire on federal land and continued clearcutting elsewhere. Indeed, the NWFP anticipated that reversing declines of older forests would take time. Overall, the early-seral ecosystem area was stable, but declined in two ecoregions-the Coast Range and Cascades-along with early-seral bird populations. Although the NWFP halted clearcutting on federal land, this has so far been insufficient to reverse declines in older-forest-associated bird populations. These findings underscore the importance of continuing to prioritize older forests under the NWFP and ensuring that the recently proposed creation of early-seral ecosystems does not impede the conservation and development of older-forest structure.

Reconciling biodiversity with timber production and revenue via an intensive forest management experiment.

Understanding how land-management intensification shapes the relationships between biodiversity, yield, and economic benefit is critical for managing natural resources. Yet, manipulative experiments that test how herbicides affect these relationships are scarce, particularly in forest ecosystems where considerable time lags exist between harvest revenue and initial investments. We assessed these relationships by combining 7 yr of biodiversity surveys (>800 taxa) and forecasts of timber yield and economic return from a replicated, large-scale experiment that manipulated herbicide application intensity in operational timber plantations. Herbicides reduced species richness across trophic groups (-18%), but responses by higher-level trophic groups were more variable (0-38% reduction) than plant responses (-40%). Financial discounting, a conventional economic method to standardize past and future cash flows, strongly modified biodiversity-revenue relationships caused by management intensity. Despite a projected 28% timber yield gain with herbicides, biodiversity-revenue trade-offs were muted when opportunity costs were high (i.e., economic discount rates ≥7%). Although herbicides can drive biodiversity-yield trade-offs, under certain conditions, financial discounting provides opportunities to reconcile biodiversity conservation with revenue.

The Role of the Striatum in Learning to Orthogonalize Action and Valence: A Combined PET and 7 T MRI Aging Study.

Pavlovian biases influence instrumental learning by coupling reward seeking with action invigoration and punishment avoidance with action suppression. Using a probabilistic go/no-go task designed to orthogonalize action (go/no-go) and valence (reward/punishment), recent studies have shown that the interaction between the two is dependent on the striatum and its key neuromodulator dopamine. Using this task, we sought to identify how structural and neuromodulatory age-related differences in the striatum may influence Pavlovian biases and instrumental learning in 25 young and 31 older adults. Computational modeling revealed a significant age-related reduction in reward and punishment sensitivity and marked (albeit not significant) reduction in learning rate and lapse rate (irreducible noise). Voxel-based morphometry analysis using 7 Tesla MRI images showed that individual differences in learning rate in older adults were related to the volume of the caudate nucleus. In contrast, dopamine synthesis capacity in the dorsal striatum, assessed using [18F]-DOPA positron emission tomography in 22 of these older adults, was not associated with learning performance and did not moderate the relationship between caudate volume and learning rate. This multiparametric approach suggests that age-related differences in striatal volume may influence learning proficiency in old age.

Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events.

The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic.

Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.

Synergistic effects of climate and land-use change influence broad-scale avian population declines.

Climate and land-use changes are expected to be the primary drivers of future global biodiversity loss. Although theory suggests that these factors impact species synergistically, past studies have either focused on only one in isolation or have substituted space for time, which often results in confounding between drivers. Tests of synergistic effects require congruent time series on animal populations, climate change and land-use change replicated across landscapes that span the gradient of correlations between the drivers of change. Using a unique time series of high-resolution climate (measured as temperature and precipitation) and land-use change (measured as forest change) data, we show that these drivers of global change act synergistically to influence forest bird population declines over 29 years in the Pacific Northwest of the United States. Nearly half of the species examined had declined over this time. Populations declined most in response to loss of early seral and mature forest, with responses to loss of early seral forest amplified in landscapes that had warmed over time. In addition, birds declined more in response to loss of mature forest in areas that had dried over time. Climate change did not appear to impact populations in landscapes with limited habitat loss, except when those landscapes were initially warmer than the average landscape. Our results provide some of the first empirical evidence of synergistic effects of climate and land-use change on animal population dynamics, suggesting accelerated loss of biodiversity in areas under pressure from multiple global change drivers. Furthermore, our findings suggest strong spatial variability in the impacts of climate change and highlight the need for future studies to evaluate multiple drivers simultaneously to avoid potential misattribution of effects.