The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Utility of livestock-protection dogs for deterring wildlife from cattle farms

Context. Livestock producers worldwide are negatively affected by livestock losses because of predators and wildlife transmitted diseases. In the western Great Lakes Region of the United States, this conflict has increased as grey wolf (Canis lupus) populations have recovered and white-tailed deer (Odocoileus virginianus) have served as a wildlife reservoir for bovine tuberculosis (Myobacterium bovis). Aims. We conducted field experiments on cattle farms to evaluate the effectiveness of livestock-protection dogs (LPDs) for excluding wolves, coyotes (C. latrans), white-tailed deer and mesopredators from livestock pastures. Methods. We integrated LPDs on six cattle farms (treatment) and monitored wildlife use with tracking swaths on these farms, concurrent with three control cattle farms during 2005–2008. The amount of time deer spent in livestock pastures was recorded using direct observation. Key results. Livestock pastures protected by LPDs had reduced use by these wildlife compared with control pastures not protected by LPDs. White-tailed deer spent less time in livestock pastures protected by LPDs compared with control pastures not protected by LPDs. Conclusions. Our research supports the theory that LPDs can be an effective management tool for reducing predation and disease transmission. We also demonstrate that LPDs are not limited to being used only with sheep and goats; they can also be used to protect cattle. Implications. On the basis of our findings, we support the use of LPDs as a proactive management tool that producers can implement to minimize the threat of livestock depredations and transmission of disease from wildlife to livestock. LPDs should be investigated further as a more general conservation tool for protecting valuable wildlife, such as ground-nesting birds, that use livestock pastures and are affected by predators that use these pastures

Good Fences Make Good Neighbors: Implementation of Electric Fencing for Establishing Effective Livestock-Protection Dogs

To be effective, livestock protection dogs (LPDs) must be carefully integrated with the livestock they will be protecting. Others have developed guidelines to assist producers in this training and assimilation process. In many areas fencing is necessary; however, guidelines for containing LPDs and their livestock behind electric fencing are lacking. We present results from larger projects involving LPDs where we encountered issues with fencing and preventing LPDs from roaming from their owner’s property. We found that ranging and escaping from pastures was exhibited by LPDs that were not properly introduced and trained to electric fencing at an early age. LPDs that were trained strategically to respect electric fencing were effective guardians and did not leave livestock pastures

Utility of livestock-protection dogs for deterring wildlife from cattle farms

Abstract Context. Livestock producers worldwide are negatively affected by livestock losses because of predators and wildlifetransmitted diseases. In the western Great Lakes Region of the United States, this conflict has increased as grey wolf (Canis lupus) populations have recovered and white-tailed deer (Odocoileus virginianus) have served as a wildlife reservoir for bovine tuberculosis (Myobacterium bovis). Aims. We conducted field experiments on cattle farms to evaluate the effectiveness of livestock-protection dogs (LPDs) for excluding wolves, coyotes (C. latrans), white-tailed deer and mesopredators from livestock pastures. Methods. We integrated LPDs on six cattle farms (treatment) and monitored wildlife use with tracking swaths on these farms, concurrent with three control cattle farms during [2005][2006][2007][2008]. The amount of time deer spent in livestock pastures was recorded using direct observation. Key results. Livestock pastures protected by LPDs had reduced use by these wildlife compared with control pastures not protected by LPDs. White-tailed deer spent less time in livestock pastures protected by LPDs compared with control pastures not protected by LPDs. Conclusions. Our research supports the theory that LPDs can be an effective management tool for reducing predation and disease transmission. We also demonstrate that LPDs are not limited to being used only with sheep and goats; they can also be used to protect cattle. Implications. On the basis of our findings, we support the use of LPDs as a proactive management tool that producers can implement to minimise the threat of livestock depredations and transmission of disease from wildlife to livestock. LPDs should be investigated further as a more general conservation tool for protecting valuable wildlife, such as ground-nesting birds, that use livestock pastures and are affected by predators that use these pastures

Are Viable Non-Lethal Management Tools Available for Reducing Wolf-Human Conflict? Preliminary Results from Field Experiments

Wolf-caused depredation results in substantial economic loss to individual farmers and can lead to greater public animosity towards wolves (i.e., reduction in social tolerance) and the agencies that manage depredations. Using an experimental design in field trials, we are testing shock collars, fladry, and livestock guarding dogs to determine if they are effective in reducing wolf use of areas in Wisconsin and Michigan. During 2003-2004, we equipped 5 wolves with shock collars and found that a 14-day shock period resulted in a decline in wolf use of baited sites by 50% compared to control wolves that increased visitation to baited sites by 18%. During 2005, we found that all pack members in shock-collared wolf packs (n = 5) avoided shock sites for over 60 days after being exposed to a 40-day shock period. During 2004-2005, we found that fladry offered farms at least 90 days of protection from wolves. During 2006-2008, we are conducting field trials with livestock guarding dogs on Michigan farms using an experimental design protocol and additional field trials of shock collars in Wisconsin. Our preliminary data suggest that shock collars and fladry may reduce wolf use of areas within their pack territories. Results of this research will provide important guidelines for implementing potential non-lethal management measures in areas wolves have recolonized or will likely recolonize in the near future and/or where wolves are being reintroduced

Are Viable Non-Lethal Management Tools Available for Reducing Wolf-Human Conflict? Preliminary Results from Field Experiments

Wolf-caused depredation results in substantial economic loss to individual farmers and can lead to greater public animosity towards wolves (i.e., reduction in social tolerance) and the agencies that manage depredations. Using an experimental design in field trials, we are testing shock collars, fladry, and livestock guarding dogs to determine if they are effective in reducing wolf use of areas in Wisconsin and Michigan. During 2003-2004, we equipped 5 wolves with shock collars and found that a 14-day shock period resulted in a decline in wolf use of baited sites by 50% compared to control wolves that increased visitation to baited sites by 18%. During 2005, we found that all pack members in shock-collared wolf packs (n = 5) avoided shock sites for over 60 days after being exposed to a 40-day shock period. During 2004-2005, we found that fladry offered farms at least 90 days of protection from wolves. During 2006-2008, we are conducting field trials with livestock guarding dogs on Michigan farms using an experimental design protocol and additional field trials of shock collars in Wisconsin. Our preliminary data suggest that shock collars and fladry may reduce wolf use of areas within their pack territories. Results of this research will provide important guidelines for implementing potential non-lethal management measures in areas wolves have recolonized or will likely recolonize in the near future and/or where wolves are being reintroduced