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Jingwen Yao¹, Melanie A. Morrison^1,2, Angela Jakary¹, Sivakami Avadiappan¹, Julia Glueck³, Theresa Driscoll³, Michael Geschwind³, Alexandra Nelson³, Duan Xu^1,2, Christopher P. Hess^1,3, and Janine M. Lupo^1,2
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²UCSF/UCB Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA, United States, ³Department of Neurology, University of California, San Francisco, San Francisco, CA, United States

Keywords: Neurodegeneration, Neurodegeneration, Huntington's disease, Movement disorder

We used QSM and DTI at 7T to investigate iron dysregulation and microstructure disruption in subcortical regions in Huntington’s disease (HD). We observed significant volume loss and increased iron deposition in the striatum and globus pallidus, and increased FA in the striatum. The deep cerebellar nuclei (dentate nuclei) showed a unique transient increase in volume and susceptibility in premanifest patients, implicating it as a new marker of HD disease progression that is sensitive to the pre-symptomatic window of HD. We also found varying relationships between imaging features in different brain regions, warranting further analyses of subregional changes.

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Joëlle van Rijswijk^1,2, Nicholas Vidas-Guscic^1,2, Johan Van Audekerke^1,2, Tamara Vasilkovska^1,2, Dorian Pustina³, Haiying Tang³, Roger Cachope³, Deanna M. Marchionini³, Ignacio Munoz-Sanjuan³, Annemie Van der Linden^1,2, Mohit H Adhikari^1,2, and Marleen Verhoye^1,2
1Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium, ²µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium, ³CHDI Management/CHDI Foundation, Princeton, NJ, United States

Keywords: Neurodegeneration, Diffusion/other diffusion imaging techniques, Huntington's Disease

Huntington’s disease (HD) is a neurodegenerative disorder for which no cure is available. There is an urgent need to find early biomarkers which are sensitive enough to determine and follow up the efficacy of novel therapies. In this study, we present the outcome of a treatment study in the LacQ140 HD mouse model using diffusion tensor/kurtosis imaging (DTI/DKI) and fixel-based analysis (FBA). We observed that early, moderate lowering of mutant Huntingtin (mHtt) rescues structural alterations measured in this mouse model with diffusion MRI in the olfactory bulb and striatum, which are prominent regions affected in HD.

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Chunxia Li¹ and Xiaodong Zhang^1
1Emory National Primate Research Center, Emory University, Atlanta, GA, United States

Keywords: Neurodegeneration, Spectroscopy, Huntington's disease

Previous studies have demonstrated in vivo MRS could be an effective approach to assess the  metabolite changes in Huntington Disease (HD)  patients and models. However,  its sensitivity to detect the metabolite abnormality is still in dispute. The metabolic changes in the striatum of transgenic monkeys of HD were investigated with MRS from 12 to 60 months of age here. A progressive and significant reduction of NAA/tCr and NAA/tCho in striatum was observed at 30 and 36 months and old, respectively, suggesting the sensitivity of the in vivo MRS to assess the neurochemical alteration in the evolution of the disease.

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Alireza Abaei¹, Stefano Antonucci², Jelena Scekic-Zahirovic², Florian olde Heuvel², Francesco Roselli², and Volker Rasche^1
1Core Facility Small Animal Imaging (CF-SANI), University of Ulm, Ulm, Germany, ²German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany

Keywords: Neurodegeneration, Preclinical, ultra-high resolution neuro neuroimaging

This study aims at demonstrating the feasibility of ex vivo MRI for structural imaging of brain. High spatial resolution in the range of 15-20 µm is obtained by an optimized FLASH sequence together with a cryogenically cooled RF coil. A 15µm-resolution was obtained for the brain, revealing cortical grey matter lamination, white matter and vascular architecture. As proof of concept, we showed in an Amyotrophic Lateral Sclerosis ( FUSΔNLS) mouse the pattern of atrophy as proxy of vulnerability using high degree of anatomical granularity. Overall, we demonstrate an ex-vivo MRI strategy with histology-grade resolution, comprehensive and  non-destructive brain sampling.  

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Emma L Thomson^1,2, Elizabeth Powell¹, Claudia A M Gandini Wheeler-Kingshott^3,4,5, and Geoff J M Parker^1,6,7
1Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ²UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, London, United Kingdom, ³NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, London, United Kingdom, ⁴Department of Brain & Behavioural Sciences, University of Pavia, Pavia, Italy, ⁵Brain Connectivity Centre Research Department, IRCCS Mondino Foundation, Pavia, Italy, ⁶NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, London, United Kingdom, ⁷Bioxydyn Limited, Manchester, United Kingdom

Keywords: Neurodegeneration, Blood vessels

Using magnetic resonance fingerprinting (MRF), we propose a method for regional quantification of blood volume (ν_b) and BBB water exchange (by quantifying capillary water residence time, τ_b), as a metric of BBB function/dysfunction. A single axial slice was acquired for seven healthy volunteers using an MRF SPGR sequence. Matching to a precomputed dictionary was performed to simultaneously quantify intra and extravascular T₁, B₁⁺, ν_b, and τ_b. Initial findings in volunteers show that it is possible to quantify these five parameters simultaneously. Our results show promise for patient studies of blood-brain barrier disruption.

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Swati Rane Levendovszky¹, Lena Vaclavu², Jaqueline Flores¹, Elaine Peskind³, Jeffrey Iliff³, and Matthias J.P. van Osch^2
1Radiology, University of Washington School of Medicine, Seattle, WA, United States, ²C.J. Gorter MRI Center, Radiology, Leiden University Medical Center, Leiden, Netherlands, ³Mental Illness Research, Education and Clinical Center, VA Puget Sound, Seattle, WA, United States

Keywords: Neurodegeneration, Perfusion, sleep, aging

We applied multi-echo Hadamard encoded ASL imaging to study blood flow (CBF) and trans-endothelial exchange of water (T_ex) as markers of vascular function to study two common risk factors of dementia; aging and sleep deprivation. We found that older adults had significantly lower CBF, and shorter T_ex compared to young adults. In the same young adults, we compared CBF and T_ex after a normal night of sleep and after sleep deprivation. Both CBF and T_ex were insignificantly lower when measured after sleep deprivation compared to measurements after normal sleep.

Beatriz Padrela¹, Lyduine E Collij¹, Luigi Lorenzini¹, Silvia Ingala¹, Carole Sudre¹, Pieter Jelle Visser², Anouk den Braber², Frederik Barkhof^1,3, Jan Petr⁴, and Henk J.M.M. Mutsaerts^1
1Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands, ²Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Location VUmc, Alzheimer Center, Amsterdam, Netherlands, ³University College London, Centre for Medical Image Computing (CMIC), London, United Kingdom, ⁴Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

Keywords: Neurodegeneration, Perfusion, Cerebral blood flow, Dementia

Arterial transit artifacts (ATAs) in arterial spin labeling (ASL) images are common in populations with prolonged arterial transit time (ATT) and may be associated with vascular insufficiency. The spatial coefficient of variance (sCoV) of ASL images can quantify the presence of these artifacts. Vascular insufficiency could contribute to the development of white matter hyperintensities (WMH), a common marker of cerebral small vessel disease. We demonstrated that baseline sCoV of CBF is associated with WMH at baseline and predicts WMH volume change, in a cognitively unimpaired population of 88 subjects.

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Jie Song¹, Wen Shi², Kaisha Hazel³, George Pottanat³, Ebony Jones³, Cuimei Xu³, Doris Lin³, Sevil Yasar⁴, Marilyn Albert⁵, Hanzhang Lu³, and Dengrong Jiang^3
1Department of Biomedical Engineering, Johns Hopkins University School of Engineering, Baltimore, MD, United States, ²Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States, ⁵Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Neurodegeneration, Aging

Aging is a multifaceted process involving both structural and metabolic alterations. Cerebral oxygen-extraction-fraction (OEF) is an important physiological parameter indexing the brain’s oxygen metabolism. In this work, we assessed regional OEF in young and older adults, and investigated its associations with aging and white-matter-hyperintensities. We observed significant age-related increase in cortical OEF but not in subcortical OEF, suggesting that aging may have different effects on tissue metabolism in cortical and subcortical regions. Furthermore, we found a significant inverse correlation of WMH with OEF in internal-cerebral-veins, implying that OEF of subcortical structures may be useful in predicting WMH.

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Bedaballi Dey^1,2, Dipak Roy¹, Sumana Chakravarty^2,3, Ghanshyman Swarup¹, Arvind Kumar^1,2, and Anant Bahadur Patel^1,2
1CSIR-Centre for Cellular & Molecular Biology (CCMB), Hyderabad, India, ²Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India, ³CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, India

Keywords: Neurodegeneration, Spectroscopy, Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset progressive motor neurodegenerative disease. To study whether in vivo loss of the multifunctional adaptor protein Optineurin (OPTN) triggers ALS, a whole-body optineurin knock-out (Optn KO) mice was generated. In the absence of a clinical phenotype, we investigated the role of chronic stress as a potential ‘determinant’ of motor phenotype in Optn deficient background. Progressive motor impairment was observed after 30 days from chronic variable mild stress (CVMS) exposure in KO stressed mice. This occurs as a result of neurodegeneration and reactive gliosis associated with neuronal glucose hypometabolism and astroglial hypermetabolism.

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Ben R Dickie¹, Duncan Forster¹, Abigail Bryce-Atkinson^2,3, Izabelle Lövgren^2,3, Azadeh Abravan⁴, Marcel van Herk^2,3, and Kaye Williams^5
1Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK, Manchester, United Kingdom, ²Division of Cancer Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK, Manchester, United Kingdom, ³Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom, Manchester, United Kingdom, ⁴Division of Cancer Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK, Manchester, UT, United Kingdom, ⁵Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK, Manchester, United Kingdom

Keywords: Neurodegeneration, Radiotherapy

Approximately 50-90% of patients that survive treatment for brain tumours experience dementia-like cognitive impairments. Here we use MRI and behavioural testing to assess longitudinal changes to brain macro- and microstructure and cognitive dysfunction following hemi-brain radiotherapy. We show shrinkage of cortical and hippocampal regions in the irradiated hemisphere, and expansion of cortical tissue in the non-irradiated hemisphere relative to non-irradiated control mice. Brain microstructure was also changed including increases in gray matter diffusivity, and decreases in white matter fractional anisotropy. Changes on MRI were accompanied by early and persistent deficits in novel object recognition.

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Mihika Gangolli^1,2,3, Sinisa Pajevic^4,5, Elizabeth B. Hutchinson^5,6, Joong Hee Kim^1,2,7, Dan Benjamini^1,8, and Peter J. Basser^1,5
1Center for Neuroscience and Regenerative Medicine, Bethesda, MD, United States, ²The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States, ³Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States, ⁴Section on Critical Brain Dynamics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, ⁵Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States, ⁶Biomedical Engineering, University of Arizona, Tucson, AZ, United States, ⁷Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, ⁸Multiscale Imaging and Integrative Biophysics Unit, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States

Keywords: Neurodegeneration, Diffusion/other diffusion imaging techniques

Propagator metrics computed from high spatial resolution diffusion MRI data are correlated with histopathological assessments of phosphorylated tau (p-tau) and astrogliosis in tissue specimen with a diagnosis of Stage III/IV chronic traumatic encephalopathy (CTE). Region of interest based analysis showed significant correlations of p-tau with non-Gaussianity (NG) in deep cortical gray matter and of propagator anisotropy (PA) with astrogliosis in superficial cortical white matter. An unsupervised clustering approach with PA and NG as inputs is then used to segment MR data of tissue specimen into clusters to determine whether propagator metrics can be utilized to detect underlying pathology.

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Yaxuan Wang¹, Fenghua Long¹, Qiyong Gong¹, Su Lui¹, and Fei Li^1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China., Chengdu, China

Keywords: Neurodegeneration, Brain Connectivity

We performed a meta-analysis to investigate shared and different alterations of resting-state functional connectivity (rsFC) for default mode network (DMN) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We found both patients with MCI and AD showed hypoconnectivity within DMN in bilateral medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) and precuneus/posterior cingulate gyrus (PCC), indicating possibly shared neuropathologic mechanism underlying common cognitive dysfunction. Moreover, we identified distinct alterations of rsFC for DMN in some brain regions, which suggested potential imaging markers to distinguish the two diseases.

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Aurea Martins Bach¹, Cristiana Tisca¹, Mohamed Tachrount¹, Carmelo Milioto^2,3, Mireia Carcolé^2,3, Shoshana Spring⁴, Remya R. Nair^5,6, Thomas J. Cunningham^6,7, Elizabeth M. C. Fisher⁸, Adrian M. Isaacs^2,3, Brian J. Nieman⁴, Jason Lerch¹, and Karla Miller^1
1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²UK Dementia Research Institute at UCL, Faculty of Brain Sciences, University College London, London, United Kingdom, ³Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, ⁴Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada, ⁵Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ⁶Mammalian Genetics Unit, MRC Harwell Institute, Oxford, United Kingdom, ⁷MRC Prion Unit and Institute of Prion diseases, University College London, London, United Kingdom, ⁸Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom

Keywords: Neurodegeneration, Preclinical

Amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTD) form a disease spectrum with shared clinical, pathological and genetic features. The most common mutations in ALS/FTD are in the genes C9Orf72, TARDBP and FUS. We used post-mortem diffusion kurtosis imaging to assess microstructure imaging phenotypes in mouse models of ALS/FTD with mutations in these genes. While mice with mutation in Tardbp presented reduced FA and MO in various white matter tracts, no difference could be detected in mice with mutation in Fus, and increased MO in a portion of the corpus callosum was observed in mice with mutation in C9orf72.

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Jingli Chen^1,2, Yarui Wei^1,2, Kangkang Xue^1,2, and Jingliang Cheng^1,2
1Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, ²Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Magnetic Resonance Imaging, Zhengzhou, China

Keywords: Neurodegeneration, Gray Matter, gray matter volume / early-onset schizophrenia / adult-onset schizophrenia /neurodevelopment / visual perception / visual cognitive

We aimed to investigate the interaction characteristics of schizophrenia and onset age and its underlying molecular mechanisms by using T1-weighted high-resolution magnetic resonance imaging (3DT1) and the JuSpace toolbox. 150 first-episode drug-naïve schizophrenia and 119 matched normal controls were recruited and underwent 3DT1 scans. Our results show that the two main effects of factors and interaction effect in gray matter volume and their underlying molecular mechanisms have varying degrees of specificity changes. Particularly, the abnormality of the visual perception system and higher visual cognitive functions in early-onset schizophrenia (EOS) have guiding significance for the mechanism and treatment of EOS.

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Christopher Samuel Parker¹, Neil P Oxtoby¹, Daniel C Alexander¹, and Hui Zhang^1
1Centre for Medical Image Computing, Department of Computer Science, UCL, London, UK, London, United Kingdom

Keywords: Neurodegeneration, Modelling, Disease progression

S-EBM generalises the event-based model (EBM) of disease progression for simultaneous events. In synthetic data, S-EBM can tell the difference between simultaneous and non-simultaneous events under a range of experimental conditions. In comparison to conventional EBM, S-EBM avoids artificial serial orderings, permitting more accurate and parsimonious descriptions of disease progression. When applied to real Alzheimer’s disease biomarker data, S-EBM estimates a sequence containing neurologically plausible simultaneous events which more closely explain the data than conventional EBM. S-EBM may be applied to recover novel patterns of disease progression thereby informing our understanding of disease evolution.

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James Lo^1,2, Eric Y. Chang^1,3, Jiang Du^1,2,3, Graeme M Bydder¹, and Yajun Ma^1
1Department of Radiology, University of California San Diego, San Diego, CA, United States, ²Department of Bioengineering, University of California San Diego, San Diego, CA, United States, ³Radiology Service, Veteran Affairs San Diego Healthcare System, San Diego, CA, United States

Keywords: Neurodegeneration, Quantitative Imaging, Myelin

In this study, we developed a comprehensive MR imaging protocol to quantify all the major components of the brain. This protocol includes four different kinds of sequences: a magnetization transfer prepared Cones (MT-Cones) for two-pool MT modeling, a short-TR adiabatic inversion-recovery prepared Cones (STAIR-Cones) for myelin water imaging, a proton-density weighted Cones (PDw-Cones) for total water imaging, and a highly T₂ weighted Cones (T₂w-Cones) for extracellular water imaging. Using a combination of these techniques, we successfully quantified the proton fractions of brain macromolecules, myelin water, intracellular water, and extracellular water components in three healthy volunteers with a 3T clinical scanner.  

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Arash Forodighasemabadi^1,2,3,4, Lucas Soustelle^1,2, Olivier M. Girard^1,2, Thomas Troalen⁵, Jean-Philippe Ranjeva^1,2, Guillaume Duhamel^1,2, and Virginie Callot^1,2,4
1Aix-Marseille Univ, CNRS, CRMBM, Marseille, France, ²APHM, Hopital Universitaire Timone, CEMEREM, Marseille, France, ³Aix-Marseille Univ, Université Gustave Eiffel, LBA, Marseille, France, ⁴iLab-Spine International Associated Laboratory, Montreal, Canada, Marseille, France, ⁵Siemens Healthcare SAS, Saint-Denis, France

Keywords: Neurodegeneration, Aging

Inhomogeneous Magnetization Transfer (ihMT) has shown to be a biomarker of myelin with enhanced specificity as compared to conventional MT. To compensate for B₁⁺ and T₁ effects, a 3D ihMT-RAGE sequence with an ihMTsat framework has recently been proposed.

In this study, ihMTsat was used in combination with an optimized MP2RAGE sequence to study both brain and spinal cord adulthood aging process.

The ihMTsat and R₁=1/T₁ metrics followed an inverse U-shaped evolution with age in different ROIs, from which a maturation age was extracted. A multiparametric (R₁,ihMTsat) voxel-wise analysis revealed significant age effect in the microstructure of different cord tracts.

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Loretta Donaldson¹, Parimal Joshi¹, Lincoln Kartchner¹, Sara Akar¹, and Peiying Liu^1
1Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, Baltimore, MD, United States

Keywords: Neurodegeneration, fMRI (task based)

Age-related changes in emotional circuitry have been studied using BOLD fMRI and revealed age-related increases in the activation of the prefrontal cortex and inconsistent findings in the amygdala. Previous emotional aging studies did not account for vascular aging which causes a reduction in cerebrovascular reactivity (CVR). Using picture viewing task fMRI and gas inhalation MRI, the fMRI signals are calibrated by the vascular measures to improve the inference of neural activity. After accounting for vascular changes, age-invariant activity was seen in the amygdala, and increased age-related activation of prefrontal regions was observed compared to activation before vascular correction.

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Ching-Wen Chang^1,2, Yi-Chen Lin¹, Chiung-Yuan Ko³, Yu-Chun Lo³, Ting-Chieh Chen¹, Ssu-Ju Li¹, Mu-Hua Wang¹, Tsai-Yu Cho¹, Sheng-Huang Lin^4,5, and You-Yin Chen^1,3
1Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan, ²Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan, ³Ph.D. Program in Medical Neuroscience, Taipei Medical University, Taipei, Taiwan, ⁴Department of Neurology, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, ⁵Department of Neurology, Tzu Chi University, Hualien, Taiwan

Keywords: Neurodegeneration, fMRI, Nucleus Basalis of Meynert

Alzheimer’s disease (AD) is an intricate neurodegenerative disease. Nucleus Basalis of Meynert (NBM), a key region of the cholinergic system that provides acetylcholine to cortex, has been shown to be target for deep brain stimulation (DBS) in AD.  The 5×FAD mouse model was used to investigate the change of behavioral tasks, resting-state functional MRI, and acetylcholinesterase (AChE)  assay were applied in this study. We found that NBM-DBS may play an important role in modulating cognitive function and spatial working memory in 5×FAD mice. Increasing functional connectivity and decreasing AChE activity may be the biomarkers for AD individuals.