The effects of glycine on auditory mismatch negativity in schizophrenia.

Glycine increases N-methyl-d-aspartate receptor (NMDAR) mediated glutamatergic function. Mismatch negativity (MMN) is a proposed biomarker of glutamate-induced improvements in clinical symptoms, however, the effect of glycine-mediated NMDAR activation on MMN in schizophrenia is not well understood. This study aimed to determine the effects of acute and 6-week chronic glycine administration on MMN in schizophrenia patients.

Evidence for a differential contribution of early perceptual and late cognitive processes during encoding to episodic memory impairment in schizophrenia.

Objectives: Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia.

Methods: Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant.

White matter correlates of episodic memory encoding and retrieval in schizophrenia.

Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and are a potential endophenotype of the disorder. The current study investigated the neuroanatomical correlates of EM encoding and retrieval in SZ with structural magnetic resonance and diffusion tensor imaging (DTI) measures in 22 patients with SZ and 22 age- and gender-matched healthy controls. Tract-based Spatial Statistics (TBSS) was used to investigate microstructural alterations in white matter (WM), while FreeSurfer surface-based analysis was used to determine abnormalities in grey matter (GM) and WM volumetrics and cortical thickness.

The relevance of attention in schizophrenia P50 paired stimulus studies.

Objective: P50 suppression refers to the P50 ERP amplitude-reduction to the second (S2) relative to the first (S1) of identical brief auditory stimuli (SOA=500ms). Its reduction in schizophrenia is argued to represent impaired inhibitory input (II) mechanisms. Enhancing attention enhances II functionality (reducing S2P50 amplitude and increasing P50 difference) in healthy subjects.

Age effects on cortical thickness in cognitively normal elderly individuals.

Background/aims: Atrophy in both grey and white matter is found in normal aging. The prefrontal cortex and the frontal lobe white matter are thought to be the most affected regions. Our aim was to examine the effects of normal aging on cortical grey matter using a 3D quantitative cortical mapping method.

Mapping cortical atrophy in Parkinson's disease patients with dementia.

Background: Cognitive impairment is very common in patients with Parkinson's disease (PD). Brain changes accompanying cognitive decline in PD are still not fully established.

Methods: We applied cortical pattern matching and cortical thickness analyses to the three-dimensional T1-weighted brain MRI scans of 14 age-matched cognitively normal elderly (NC), 12 cognitively normal PD (PDC), and 11 PD dementia (PDD) subjects.

Ventricular enlargement and its clinical correlates in the imaging cohort from the ADCS MCI donepezil/vitamin E study.

We analyzed the baseline and 3-year T1-weighted magnetic resonance imaging data of 110 amnestic mild cognitive impairment (MCI) participants with minimal hippocampal atrophy at baseline from the Alzheimer's Disease Cooperative Study group MCI Donepezil/Vitamin E trial. Forty-six subjects converted to Alzheimer disease (AD) (MCIc), whereas 64 remained stable (MCInc). We used the radial distance technique to examine the differences in lateral ventricle shape and size between MCIc and MCInc and the associations between ventricular enlargement and cognitive decline.

Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease.

Alzheimer disease (AD) is the most common type of dementia worldwide. Hippocampal atrophy and ventricular enlargement have been associated with AD but also with normal aging. We analyzed 1.

Cortical and hippocampal atrophy in patients with autosomal dominant familial Alzheimer's disease.

Background: Both familial and sporadic Alzheimer's disease (AD) result in progressive cortical and subcortical atrophy. Familial autosomal dominant AD (FAD) allows us to study AD brain changes presymptomatically.

Methods: 33 subjects at risk for FAD (25 for PSEN1 and 8 for APP mutations; 22 mutation carriers and 11 controls) and 3 demented PSEN1 mutation carriers underwent T(1)-weighted MPRAGE 1.

Effects of ApoE4 and maternal history of dementia on hippocampal atrophy.

We applied an automated hippocampal segmentation technique based on adaptive boosting (AdaBoost) to the 1.5 T magnetic resonance imaging (MRI) baseline and 1-year follow-up data of 243 subjects with mild cognitive impairment (MCI), 96 with Alzheimer's disease (AD), and 145 normal controls (NC) scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). MCI subjects with positive maternal history of dementia had smaller hippocampal volumes at baseline and at follow-up, and greater 12-month atrophy rates than subjects with negative maternal history.

3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects.

Cerebrospinal fluid (CSF) measures of Ab and tau, Pittsburgh Compound B (PIB) imaging and hippocampal atrophy are promising Alzheimer's disease biomarkers yet the associations between them are not known. We applied a validated, automated hippocampal labeling method and 3D radial distance mapping to the 1.5T structural magnetic resonance imaging (MRI) data of 388 ADNI subjects with baseline CSF Ab(42), total tau (t-tau) and phosphorylated tau (p-tau(181)) and 98 subjects with positron emission tomography (PET) imaging using PIB.

Hippocampal, caudate, and ventricular changes in Parkinson's disease with and without dementia.

Parkinson's disease (PD) has been associated with mild cognitive impairment (PDMCI) and with dementia (PDD). Using radial distance mapping, we studied the 3D structural and volumetric differences between the hippocampi, caudates, and lateral ventricles in 20 cognitively normal elderly (NC), 12 cognitively normal PD (PDND), 8 PDMCI, and 15 PDD subjects and examined the associations between these structures and Unified Parkinson's Disease Rating Scale (UPDRS) Part III:motor subscale and Mini-Mental State Examination (MMSE) performance. There were no hippocampal differences between the groups.

3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.

We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up.

Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects.

We used a previously validated automated machine learning algorithm based on adaptive boosting to segment the hippocampi in baseline and 12-month follow-up 3D T1-weighted brain MRIs of 150 cognitively normal elderly (NC), 245 mild cognitive impairment (MCI) and 97 Dementia of the Alzheimer's type (DAT) ADNI subjects. Using the radial distance mapping technique, we examined the hippocampal correlates of delayed recall performance on three well-established verbal memory tests--ADAScog delayed recall (ADAScog-DR), the Rey Auditory Verbal Learning Test -DR (AVLT-DR) and Wechsler Logical Memory II-DR (LM II-DR). We observed no significant correlations between delayed recall performance and hippocampal radial distance on any of the three verbal memory measures in NC.

Surface feature-guided mapping of cerebral metabolic changes in cognitively normal and mildly impaired elderly.

Purpose: The aim of this study was to investigate the longitudinal positron emission tomography (PET) metabolic changes in the elderly.

Procedures: Nineteen nondemented subjects (mean Mini-Mental Status Examination 29.4 +/- 0.

Comparison of AdaBoost and support vector machines for detecting Alzheimer's disease through automated hippocampal segmentation.

We compared four automated methods for hippocampal segmentation using different machine learning algorithms: 1) hierarchical AdaBoost, 2) support vector machines (SVM) with manual feature selection, 3) hierarchical SVM with automated feature selection (Ada-SVM), and 4) a publicly available brain segmentation package (FreeSurfer). We trained our approaches using T1-weighted brain MRIs from 30 subjects [10 normal elderly, 10 mild cognitive impairment (MCI), and 10 Alzheimer's disease (AD)], and tested on an independent set of 40 subjects (20 normal, 20 AD). Manually segmented gold standard hippocampal tracings were available for all subjects (training and testing).

Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls.

We used a new method we developed for automated hippocampal segmentation, called the auto context model, to analyze brain MRI scans of 400 subjects from the Alzheimer's disease neuroimaging initiative. After training the classifier on 21 hand-labeled expert segmentations, we created binary maps of the hippocampus for three age- and sex-matched groups: 100 subjects with Alzheimer's disease (AD), 200 with mild cognitive impairment (MCI) and 100 elderly controls (mean age: 75.84; SD: 6.

Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls.

As one of the earliest structures to degenerate in Alzheimer's disease (AD), the hippocampus is the target of many studies of factors that influence rates of brain degeneration in the elderly. In one of the largest brain mapping studies to date, we mapped the 3D profile of hippocampal degeneration over time in 490 subjects scanned twice with brain MRI over a 1-year interval (980 scans). We examined baseline and 1-year follow-up scans of 97 AD subjects (49 males/48 females), 148 healthy control subjects (75 males/73 females), and 245 subjects with mild cognitive impairment (MCI; 160 males/85 females).

Automatic subcortical segmentation using a contextual model.

Automatically segmenting subcortical structures in brain im ages has the potential to greatly accelerate drug trials and population studies of disease. Here we propose an automatic subcortical segmentation algorithm using the auto context model. Unlike many segmentation algorithms that separately compute a shape prior and an image appearance model, we develop a framework based on machine learning to learn a unified appearance and context model.

Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal.

Atrophic changes of the hippocampus are typically regarded as an early sign of Alzheimer's dementia (AD). Using the radial distance atrophy mapping approach, we compared the longitudinal MRI data of 10 cognitively normal elderly subjects who remained normal at 3-year and 6-year follow-up (NL-NL) and 7 cognitively normal elderly subjects who were diagnosed with mild cognitive impairment (MCI) 2.8 (range 2.

Validation of a fully automated 3D hippocampal segmentation method using subjects with Alzheimer's disease mild cognitive impairment, and elderly controls.

We introduce a new method for brain MRI segmentation, called the auto context model (ACM), to segment the hippocampus automatically in 3D T1-weighted structural brain MRI scans of subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In a training phase, our algorithm used 21 hand-labeled segmentations to learn a classification rule for hippocampal versus non-hippocampal regions using a modified AdaBoost method, based on approximately 18,000 features (image intensity, position, image curvatures, image gradients, tissue classification maps of gray/white matter and CSF, and mean, standard deviation, and Haar filters of size 1x1x1 to 7x7x7). We linearly registered all brains to a standard template to devise a basic shape prior to capture the global shape of the hippocampus, defined as the pointwise summation of all the training masks.

Muscarinic and nicotinic receptor modulation of object and spatial n-back working memory in humans.

Working memory impairments in the n-back task in schizophrenia have been linked to sustained deficiency in mesocortical dopamine function. More recently, abnormalities in the cholinergic system have also been documented in schizophrenia, with cortical reductions in both nicotinic and muscarinic receptors. While the cholinergic hypothesis of memory is well established, the role of cholinergic receptors in modulating n-back working memory is not known.