An Vo

The Feinstein Institute for Medical Research · Center for Neuroscience

To understand how neuroinflammation is sustained in the absence of systemic inflammation we have studied a mouse model of neuropsychiatric lupus (NPSLE) which is triggered by the penetration of neurotoxic antibodies into the hippocampus. The subsequent activation of microglia leads to dendritic pruning of hippocampal neurons. This process becomes c...

Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal syndrome for Parkinson’s disease (PD) and related 𝛼-synucleinopathies. We conducted a longitudinal imaging study of network changes in iRBD and their relationship to phenoconversion. Expression levels for the PD-related motor and cognitive networks (PDRP and PDCP) were measur...

Alzheimer’s Disease psychosis (AD + P) is characterized by accelerated cognitive decline and tau pathology. Through exploring the AD + P network (ADPN), the aim is to predict psychosis in AD and understand its mechanisms. Utilizing FDG PET scans from ADNI control and AD groups, we employed a convolutional neural network to identify and validate the...

Subthalamic nucleus deep brain stimulation (STN-DBS) alleviates motor symptoms of Parkinson’s disease (PD), thereby improving quality of life. However, quantitative brain markers to evaluate DBS responses and select suitable patients for surgery are lacking. Here, we used metabolic brain imaging to identify a reproducible STN-DBS network for which...

Psychosis that occurs over the course of Alzheimer’s disease (AD) is associated with increased caregiver burden and a more rapid cognitive and functional decline. To find new treatment targets, studies modeling psychotic conditions traditionally employ agents known to induce psychosis, utilizing outcomes with cross-species relevance, such as locomo...

Objective: To characterize a metabolic brain network associated with X-linked dystonia-parkinsonism (XDP). Methods: Thirty right-handed Filipino men with XDP (age 44.4±8.5 years) and 30 XDP-causing mutation negative healthy men from the same population (age 37.4±10.5 years) underwent [18 F]-fluorodeoxyglucose positron emission tomography. Scans...

Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is read...

Background: Although sporadic Creutzfeldt-Jakob's disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, we investigated metabolic brain network associated with s...

Background: Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge. Methods: Here, we studied the utility of a micro p...

Behavioral variant of frontotemporal dementia (bvFTD) is common among young-onset dementia patients. While bvFTD-specific multivariate metabolic brain pattern (bFDRP) has been identified previously, little is known about its temporal evolution, internal structure, effect of atrophy, and its relationship with nonspecific resting-state networks such...

Background: Metabolic brain imaging with 2-[18 F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is a supportive diagnostic and differential diagnostic tool for neurodegenerative dementias. In the clinic, scans are usually visually interpreted. However, computer-aided approaches can improve diagnostic accuracy. We aimed to build two...

Background: Idiopathic Parkinson's disease (iPD) is associated with two distinct brain networks, PD-related pattern (PDRP) and PD-related cognitive pattern (PDCP), which correlate respectively with motor and cognitive symptoms. The relationship between the two networks in individual patients is unclear. Objective: To determine whether a consiste...

The fetal brain is constantly exposed to maternal IgG before the formation of an effective blood-brain barrier (BBB). Here, we studied the consequences of fetal brain exposure to an antibody to the astrocytic protein aquaporin-4 (AQP4-IgG) in mice. AQP4-IgG was cloned from a patient with neuromyelitis optica spectrum disorder (NMOSD), an autoimmune...

Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, whether the connectivity patterns in these networks differ with disease progression compared to the beneficial adaptations that may also occur over time. To distinguish the 2 respons...

Background Mechanisms for SLE-mediated cognitive impairment (SLE-CI) include autoantibodies and inflammatory molecules normally excluded from the brain by an intact blood brain barrier (BBB). However, the BBB permeability may be altered in response to molecular signals from the periphery and activated microglia in the brain. We have hypothesized th...

Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, if connectivity patterns in these networks differ with disease progression compared to the beneficial adaptations that may also occur over time. To distinguish the two responses, we...

Spatial covariance mapping of brain activity has been used increasingly with metabolic imaging to detect and quantify abnormal disease patterns in patient populations. Metabolic topographies such as the Parkinson's disease-related pattern (PDRP), while extensively validated, require access to positron emission tomography (PET) and radiation exposur...

Cognitive dysfunction in Parkinson’s disease (PD) is associated with increased expression of the PD cognition-related pattern (PDCP), which overlaps with the normal default mode network (DMN). Here, we sought to determine the degree to which the former network represents loss of the latter as a manifestation of the disease process. To address this,...

Purpose of review: Neuropsychiatric lupus (NPSLE) comprises a disparate collection of syndromes affecting the central and peripheral nervous systems. Progress in the attribution of neuropsychiatric syndromes to SLE-related mechanisms and development of targeted treatment strategies has been impeded by a lack of objective imaging biomarkers that re...

The natural history of idiopathic Parkinson's disease (PD) varies considerably across patients. While PD is generally sporadic, there are known genetic influences: the two most common, mutations in the LRRK2 or GBA1 gene, are associated with slower and more aggressive progression, respectively. Here, we applied graph theory to metabolic brain imagi...

To address challenges in the diagnosis of cognitive dysfunction (CD) related to systemic lupus erythematosus-associated (SLE-associated) autoimmune mechanisms rather than confounding factors, we employed an integrated approach, using resting-state functional (FDG-PET) and structural (diffusion tensor imaging [DTI]) neuroimaging techniques and cogni...

Gene therapy is emerging as a promising approach for treating neurological disorders, including Parkinson’s disease (PD). A phase 2 clinical trial showed that delivering glutamic acid decarboxylase ( GAD ) into the subthalamic nucleus (STN) of patients with PD had therapeutic effects. To determine the mechanism underlying this response, we analyzed...

Objective This pilot study aimed to examine longitudinal changes in brain structure and function in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging (DTI) and neuropsychological testing. Methods Fifteen female SLE patients with no history of major neuropsychiatric (NP) manifestations had brain magnetic resonance imag...

Background Parkinson’s disease and related cognitive deficits have been associated with specific functional topographies termed functional PD-related pattern (fPDRP) and PD cognition-related pattern (fPDCP) (Vo et al., 2017). Using multivariate analysis in resting-state functional MRI data this novel approach discriminated normal controls from PD p...

It is well established that Parkinson's disease leads to impaired learning from reward and enhanced learning from punishment. The administration of dopaminergic medications reverses this learning pattern. However, few studies have investigated the neural underpinnings of these cognitive processes. In this study, using fMRI, we tested a group of Par...

In healthy subjects, brain activation in motor regions is greater during the visual perception of “natural” target motion, which complies with the two-thirds power law, than of “unnatural” motion, which does not. It is unknown whether motion perception is normally mediated by a specific network that can be altered in the setting of disease. We used...

Most existing array comparative genomic hybridization (array CGH) data processing methods and evaluation models assumed that the probability density function of noise in array CGH is a Gaussian distribution. However, in practice such noise distribution is peaky and heavy-tailed. A more accurate and sufficient model of noise in array CGH data is nec...

Spatial covariance mapping can be used to identify and measure the activity of disease-related functional brain networks. While this approach has been widely used in the analysis of cerebral blood flow and metabolic PET scans, it is not clear whether it can be reliably applied to resting state functional MRI (rs-fMRI) data. In this study, we presen...

Objective: Standardized cognitive tests and functional magnetic resonance imaging (fMRI) studies of SLE patients demonstrate deficits in working memory and executive function. These neurobehavioral abnormalities are not well studied in antiphospholipid syndrome (APS), which may occur independently of or together with SLE. This study compares an fM...

View largeDownload slide Although primary dystonia is defined by motor manifestations, non-motor involvement is increasingly recognized. Sako et al. use fMRI and DTI to study brain circuits associated with motion perception in patients with DYT1 dystonia. Results confirm that circuit abnormalities in primary dystonia are not limited to primary mot...

Abstract Studying epigenetic landscapes is important to understand the condition for gene regulation. Clustering is a useful approach to study epigenetic landscapes by grouping genes based on their epigenetic conditions. However, classical clustering approaches that often use a representative value of the signals in a fixed-sized window do not full...

TorsinA is an important protein in brain development, and plays a role in the regulation of neurite outgrowth and synaptic function. Patients with the most common form of genetic dystonia carry a mutation (DYT1) in one copy of the Tor1a gene, a 3-bp deletion, causing removal of a single glutamic acid from torsinA. Previous imaging studies have show...

Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared...

Dystonia is a brain disorder characterized by abnormal involuntary movements without defining neuropathological changes. The disease is often inherited as an autosomal-dominant trait with incomplete penetrance. Individuals with dystonia, whether inherited or sporadic, exhibit striking phenotypic variability, with marked differences in the somatic d...

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potential...

Epigenetic landscapes in the regulatory regions reflect binding condition of transcription factors (TFs) and their co-factors. Identifying epigenetic condition and its variation is important in understanding condition-specific gene regulation. Computational approaches to explore complex multi-dimensional landscapes are needed. To study epigenomic c...

Purpose: To determine brain tissue affected by dystonia by making group comparison of parameter-based diffusion tensor imaging (DTI) distributions of patients with control subjects. A 2D distribution analysis of mean diffusivity and fractional anisotropy index was used for modeling brain tissues according to the inherent diffusion characteristics....

Purpose: To make a group comparison of diffusion tensor imaging (DTI) results of dystonia patients and controls to reveal occult pathology. We propose using an early registration method that produces sharper group images and enables us to do group tractography. Materials and methods: Twelve dystonia patients manifesting the disease, seven nonman...

Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlat...

The factors that determine symptom penetrance in inherited disease are poorly understood. Increasingly, magnetic resonance diffusion tensor imaging (DTI) and PET are used to separate alterations in brain structure and function that are linked to disease symptomatology from those linked to gene carrier status. One example is DYT1 dystonia, a dominan...

With the assumptions of Gaussian as well as Gaussian scale mixture models for images in wavelet domain, marginal and joint distributions for phases of complex wavelet coefficients are studied in detail. From these hypotheses, we then derive a relative phase probability density function, which is called Vonn distribution, in complex wavelet domain....

Solenoid proteins are emerging as a protein class with properties intermediate between structured and intrinsically unstructured proteins. Containing repeating structural units, solenoid proteins are expected to share sequence similarities. However, in many cases, the sequence similarities are weak and non-detectable. Moreover, solenoids can be deg...

Peaks are the key information in mass spectrometry (MS) which has been increasingly used to discover diseases-related proteomic patterns. Peak detection is an essential step for MS-based proteomic data analysis. Recently, several peak detection algorithms have been proposed. However, in these algorithms, there are three major deficiencies: (i) beca...

In this paper, we propose the complex Gaussian scale mixture (CGSM) to model the complex wavelet coefficients as an extension of the Gaussian scale mixture (GSM), which is for real-valued random variables to the complex case. Along with some related propositions and miscellaneous results, we present the probability density functions of the magnitud...

Array-based comparative genomic hybridization (aCGH) has merged as a highly efficient technique for the detection of chromosomal imbalances. Characteristics of these DNA copy number aberrations provide the insights into cancer, and they are useful for the diagnostic and therapy strategies. In this article, we propose a statistical bivariate model f...

In this paper, we develop a new approach which exploits the probabilistic properties from the phase information of 2-D complex wavelet coefficients for image modeling. Instead of directly using phases of complex wavelet coefficients, we demonstrate why relative phases should be used. The definition, properties and statistics of relative phases of c...

Mass Spectrometry (MS) is increasingly being used to discover diseases-related proteomic patterns. The peak detection step is one of the most important steps in the typical analysis of MS data. Recently, many new algorithms have been proposed to increase true position rate with low false discovery rate in peak detection. Most of them follow two app...

In this paper, the probability distributions of relative phase are studied. We proposed von Mises and wrapped Cauchy for the probability density function (pdf) of the relative phase in complex wavelet domain. The maximum-likelihood method is used to estimate the two parameters of von Mises and wrapped Cauchy. We demonstrate that the von Mises and w...

In this paper, a new statistical model is proposed for modeling the nature images in the transform domain. We demonstrate that the von Mises distribution (VM) fits accurately the behaviors of relative phases in the complex directional wavelet subband from different nature images. Moreover, a new image feature based on the VM model is proposed for t...

Array-based comparative genomic hybridization (array CGH) is a highly efficient technique, allowing the simultaneous measurement of genomic DNA copy number at hundreds or thousands of loci and the reliable detection of local one-copy-level variations. Characterization of these DNA copy number changes is important for both the basic understanding of...

Mass Spectrometry (MS) is increasingly being used to discover disease related proteomic patterns. The peak detection step is one of most important steps in the typical analysis of MS data. Recently, many new algorithms have been proposed to increase true position rate with low false position rate in peak detection. Most of them follow two approache...

Abstract—Array based Comparative Genomic Hybridization (CGH) is a molecular cytogenetic method,for the detection of chromosomal,imbalances and it has been extensively used for studying copy number,alterations in various cancer types. Our method captures both the intrinsic spatial change of genome,hybridization intensities, and the physical distance...

In this paper, a modified version of the complex directional pyramid (PDTDFB) is proposed. Unlike the previous approach, the new FB provides approximately tight-frame decomposition. We introduced the complex Gaussian scale mixture (CGSM) for modeling the distribution of complex directional wavelet coefficients. The statistical model is then used to...

This paper discusses how to utilize both magnitude and phase information obtained from the complex directional filter bank (CDFB) for the purpose of texture image retrieval. The relative phase, which is the difference of phases between adjacent CDFB coefficients, has a linear relationship with the angle of dominant orientation within a subband. Thi...

In this paper, the shift-invariant complex directional filter bank (CDFB) is proposed for texture image retrieval. By combining the Laplacian pyramid and the CDFB, a new image representation with an overcomplete ratio of less than 8/3 is obtained. The direction subbands' coefficients are used to form a feature vector for classification. Texture ret...

In this project, a modified version of the curvelet transform is proposed for image denoising. We introduced the complex Gaussian scale mixture (CGSM) for modeling the distribution of complex curvelet coeffi- cients. The statistical model is then used to obtain the denoised coefficients from the noisy image decomposition by Bayes least squares esti...