Biomedical subjects

Howard J Aizenstein

Publications and source records attributed to Howard J Aizenstein.

16 recordsLinked to original sources

PubMed2006

Optimum template selection for atlas-based segmentation.

Atlas-based segmentation of MR brain images typically uses a single atlas (e.g., MNI Colin27) for region identification. Normal individual variations in human brain structures present a significant challenge for atlas selection. Previous researches mainly focused on how to create a specific template for different requirements (e.g., for a certain population). We address atlas selection with a different approach: instead of choosing a fixed brain atlas, we use a family of brain templates for atlas-based segmentation. For each subject and each region, the template selection method automatically chooses the 'best' template with the highest local registration accuracy, based on normalized mutual information. The region classification performances of the template selection method and the single template method were quantified by the overlap ratios (ORs) and intraclass correlation coefficients (ICCs) between the manual tracings and the respective automated labeled results. Two groups of brain images and multiple regions of interest (ROIs), including the right anterior cingulate cortex (ACC) and several subcortical structures, were tested for both methods. We found that the template selection method produced significantly higher ORs than did the single template method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at t(8)=4.353, p=0.0024; right amygdala, matched paired t test t(8)>3.175, p<0.013; for the remaining ROIs, t(8)=4.36, p<0.002). The template selection method also provided more reliable volume estimates than the single template method with increased ICCs. Moreover, the improved accuracy of atlas-based segmentation using optimum templates approaches the accuracy of manual tracing, and thus is valid for automated brain imaging analyses.

Adult↗

PubMed2006

A fully automated method for quantifying and localizing white matter hyperintensities on MR images.

White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539-544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders.

Aged↗

PubMed2006

3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry.

UNLABELLED: 35% of HIV-infected patients have cognitive impairment, but the profile of HIV-induced brain damage is still not well understood. Here we used tensor-based morphometry (TBM) to visualize brain deficits and clinical/anatomical correlations in HIV/AIDS. To perform TBM, we developed a new MRI-based analysis technique that uses fluid image warping, and a new alpha-entropy-based information-theoretic measure of image correspondence, called the Jensen-Rényi divergence (JRD). METHODS: 3D T1-weighted brain MRIs of 26 AIDS patients (CDC stage C and/or 3 without HIV-associated dementia; 47.2+/-9.8 years; 25M/1F; CD4+ T-cell count: 299.5+/-175.7/microl; log10 plasma viral load: 2.57+/- 1.28 RNA copies/ml) and 14 HIV-seronegative controls (37.6+/-12.2 years; 8M/6F) were fluidly registered by applying forces throughout each deforming image to maximize the JRD between it and a target image (from a control subject). The 3D fluid registration was regularized using the linearized Cauchy-Navier operator. Fine-scale volumetric differences between diagnostic groups were mapped. Regions were identified where brain atrophy correlated with clinical measures. RESULTS: Severe atrophy ( approximately 15-20% deficit) was detected bilaterally in the primary and association sensorimotor areas. Atrophy of these regions, particularly in the white matter, correlated with cognitive impairment (P = 0.033) and CD4+ T-lymphocyte depletion (P = 0.005). CONCLUSION: TBM facilitates 3D visualization of AIDS neuropathology in living patients scanned with MRI. Severe atrophy in frontoparietal and striatal areas may underlie early cognitive dysfunction in AIDS patients, and may signal the imminent onset of AIDS dementia complex.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Automated ROI-based brain parcellation analysis of frontal and temporal brain volumes in schizophrenia.

Structural MRI studies of schizophrenia have yielded a diversity of findings. To help characterize regional gray matter changes in schizophrenia, we used an automated region of interest (ROI)-based approach that targeted frontal and temporal regions in schizophrenia patients. The sample compromised 43 schizophrenia patients (21 chronic patients, 22 unmedicated first episode patients), 20 first episode non-schizophrenia psychosis patients and 47 comparison subjects. Automated regional volume measurement was performed in 22 ROIs, including frontal and temporal cortical subregions and hippocampus. Correlations between volume measures, duration of illness and clinical scores were evaluated. Chronic schizophrenia patients showed gray matter volume differences in left dorsolateral prefrontal cortex (DLPFC) and right supplementary motor area (SMA). First episode psychosis patients presented smaller right anterior cingulate cortex (ACC) and left DLPFC than comparison subjects. Disorganization scores and duration of illness correlated negatively with gray matter volume of DLPFC and SMA in chronic schizophrenia patients. Using an automated ROI-based method, we found volume reductions in lateral and medial frontal regions in both first episode and chronic schizophrenia. The automated ROI-based method can be used as a valid and efficient tool for quantification of regional gray matter volume in schizophrenia in multiple ROIs across the brains of large numbers of subjects.

Adult↗

PubMed2006

Ventricular volume and dementia progression in the Cardiovascular Health Study.

Elevated cerebral ventricular volume may be associated with dementia risk and progression. A fully-automated technique that agreed highly with radiological readings was used to estimate lateral ventricle volume on MR scans done at baseline in 1997-99 of 377 subjects in the Cardiovascular Health Study (CHS) from the Pittsburgh Center. 327 subjects were normal or diagnosed with mild cognitive impairment (MCI) at baseline and were evaluated 4 years later. Baseline ventricular volume was analyzed in multivariate models with age, gender, education level, presence and incidence of cerebral infarcts, and dementia category (normal, MCI, or dementia) at baseline and follow-up as fixed effects. Ventricular volume at baseline was significantly higher among subjects normal at baseline and demented 4 years later. Age, gender, education level, and dementia progression were significant factors affecting ventricular volume. Ventricular volume was higher in dementia compared to MCI, higher in MCI compared to controls, and higher in Possible-Alzheimer's-disease (AD) dementia compared to Probable-AD. Larger ventricles in healthy subjects may indicate susceptibility to, or progression of, dementia-related pathology.

Aged↗

PubMed2006

3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS.

OBJECTIVE: 40 million people worldwide are now infected with HIV/AIDS, an illness that often leads to rapidly progressing dementia and death. Even so, little is known about how AIDS affects the brain. Using computational anatomy techniques, we mapped how AIDS impacts the corpus callosum (CC) and ventricular system, two systems that show prominent changes on MRI. We (1) identified regions with greatest differences between AIDS patients and healthy controls and (2) correlated specific 3D patterns of structural differences with measures of immune system deterioration and cognitive decline. METHODS: 51 3D brain MRI scans from 30 non-demented AIDS patients (age: 43.4 years +/- 7.6 SD) and 21 HIV-seronegative controls (age: 39.5 years +/- 12.2) were aligned to ICBM standard space. 3D surface mesh reconstructions of the lateral ventricles and CC were spatially averaged and compared across diagnostic groups. Structural alterations were correlated with viral load, T cell counts, and cognitive impairment. RESULTS: Statistical maps revealed the 3D profile of ventricular expansion and callosal thinning in AIDS. Specific 3D ventricular changes were linked with immune system decline (CD4+ T cell counts; P < 0.001) and cognitive impairment (P < 0.009), but not viral load. Frontal horn maps distinguished AIDS patients from controls better than occipital and temporal horn measures. T cell decline linked with callosal thinning in anterior regions connecting frontal areas with greatest cortical atrophy. CONCLUSION: These maps (1) reveal how brain changes in HIV/AIDS relate to immune decline and impaired cognition, and, after further validation and testing, (2) may offer possible neuroimaging markers for anti-viral drug trials, which gauge how well treatments oppose disease progression in the brain.

AIDS Dementia Complex↗

PubMed2006

Quantitative comparison of AIR, SPM, and the fully deformable model for atlas-based segmentation of functional and structural MR images.

Typical packages used for coregistration in functional image analyses include automated image registration (AIR) and statistical parametric mapping (SPM). However, both methods have limited-dimension deformation models. A fully deformable model, which combines the piecewise linear registration for coarse alignment with demons algorithm for voxel-level refinement, allows a higher degree of spatial deformation. This leads to a more accurate colocalization of the functional signal from different subjects and therefore can produce a more reliable group average signal. We quantitatively compared the performance of the three different registration approaches through a series of experiments and we found that the fully deformable model consistently produces a more accurate structural segmentation and a more reliable functional signal colocalization than does AIR or SPM.

Adult↗

PubMed2005

Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline.

HIV/AIDS infection is the fourth leading cause of death worldwide, and one in every 100 adults aged 15-49 years is HIV-infected. Forty percent of AIDS patients suffer from neurological symptoms, but the selective profile of damage caused by HIV in the brain is not well understood. Here, we report 3D maps revealing how AIDS affects the human cerebral cortex, identifying the most vulnerable regions and where deficits link with cognitive decline and immune-system suppression. With high-resolution brain MRI scans, we created composite maps of cortical gray-matter thickness in 26 AIDS patients and 14 healthy controls to establish the selective pattern of brain deficits in AIDS. In AIDS, primary sensory, motor, and premotor cortices were 15% thinner. Thinner frontopolar and language cortex correlated with immune system deterioration measured through blood levels of CD4+ T lymphocytes. Prefrontal and parietal tissue loss correlated with cognitive/motor deficits. T cell depletion and cognitive impairment are, therefore, associated with specific 3D brain-deficit patterns visualized with MRI. These quantitative MRI-based maps reveal that HIV selectively damages the cortex. They provide an approach to gauge the impact of AIDS on the living brain and show that the brain is still vulnerable to infection even when patients are receiving antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Prefrontal and striatal activation during sequence learning in geriatric depression.

BACKGROUND: Frontostriatal dysfunction is a primary hypothesis for the neurocognitive changes of depression in late life. The aim of the present study was to test this hypothesis with the use of functional magnetic resonance imaging (fMRI) tasks that are known to engage the prefrontal and neostriatal cognitive circuits. METHODS: Twenty-three elderly subjects (mean age, 69.9 years) participated: 11 subjects with a current major depressive episode and 12 nondepressed elderly control subjects. Subjects underwent fMRI while performing a concurrent implicit and explicit sequence learning task. Region of interest (ROI)-based analyses were conducted, focusing on the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the neostriatum. RESULTS: As expected, both the control and depressed subjects learned the sequence during both implicit and explicit conditions. During explicit learning, decreased prefrontal activation was found in the depressed subjects, along with increased striatal activation. The increased striatal activity in the depressed subjects was due to increased activity on the trials that violated the sequence. During implicit learning, no significant differences were found between the groups in the identified ROIs. CONCLUSIONS: The increased striatal activation on trials that violated the sequence demonstrates a greater response to negative feedback for depressed compared with control subjects. Our observations of significant differences in both prefrontal and striatal regions in the depressed elderly subjects relative to elderly control subjects supports the frontostriatal dysfunction hypothesis of late-life depression.

Aged↗

PubMed2005

Prefrontal and striatal activation in elderly subjects during concurrent implicit and explicit sequence learning.

Decreased function in the prefrontal cortex (PFC) is regarded as a primary mechanism of cognitive aging. However, despite a strong association between the prefrontal cortex and the neostriatum, the role of the neostriatum in cognitive aging is less certain. In the current study, event-related functional MRI was used to distinguish the cognitive contributions of neostriatal and prefrontal function in elderly versus young subjects. Twenty healthy subjects, 9 elderly (mean age 67.6 years), and 11 young (mean age 22 years) performed a concurrent implicit and explicit sequence learning task while undergoing functional MR imaging. Both groups showed learning in both the implicit and explicit task conditions. Relative to the young subjects, the elderly subjects showed decreased activation in the left PFC during both implicit and explicit learning, decreased activation in the right putamen during implicit learning, and increased activation in the right PFC during explicit learning. Our results support the theory that changes in a network of brain regions, including the dorsolateral prefrontal cortex and the striatum, are related to cognitive aging. Moreover, these changes are observed during an implicit task, and thus do not seem to be mediated by awareness.

Adult↗

PubMed2005

Event-related functional magnetic resonance imaging investigation of executive control in very old individuals with mild cognitive impairment.

BACKGROUND: Attentional control of executive cognitive function (ECF) decreases in older individuals with Alzheimer Disease (AD). In order to examine early AD-related changes in the neural substrates of ECF attentional control, we measured activation dorsolateral prefrontal (dLPFC), posterior parietal (PPC), and anterior cingulate cortex (ACC) in adults with mild cognitively impairment (MCI) and in cognitively normal (CN) adults. METHODS: Functional magnetic resonance imaging analysis of brain activation in MCI (n = 8, mean age 79.5) and CN (n = 8 mean age 81.5) during increasing loads of attentional demands. RESULTS: MCI and CN older adults performed with similar accuracy and reaction time. MCI had greater activation than CN in PPC (right p = .03 and left p = .05) and dlPFC areas (right p = .002 and left p = .004), while activation in ACC was similar in the two groups. Response to increasing loads of the task differed by group: MCI selectively engaged bilateral PPC (right p = .03, left p = .04), while CN subjects increased bilateral dlPFC activation (right p = .005 and left p = .02) and ACC activation (p = .04). Among MCI, greater load-related changes in PPC activity were associated with smaller load-related changes in accuracy rates (r = -.85, p = .07) and greater increases in reaction times (r = .97, p = .01). In CN subjects, load-related change in PPC activation was associated with load-related change in reaction time (r = .76, p = .02) but not with changes in accuracy rates. CONCLUSIONS: PPC and dlPFC may show early functional changes associated with MCI.

Aged↗

PubMed2005

Trajectories of treatment response in late-life depression: psychosocial and clinical correlates.

The authors examined the effect of psychosocial and clinical variables on treatment response trajectory in elderly patients with major depressive disorder. Three studies provided data on treatment response in 360 elderly depressed subjects who participated in protocols using either nortriptyline or paroxetine as monotherapy or, in 2 studies, combined with interpersonal psychotherapy. Treatment response was assessed with the Hamilton Rating Scale for Depression-17 Item (HRSD-17) score over 12 weeks of acute treatment in each study. The mixture-modeling method of trajectory analysis was used to identify different subpopulations of response, and to determine whether baseline HRSD-17 score, depressive illness course (single or recurrent), current episode duration, Interpersonal Self Evaluation List-Self-esteem factor, age at study entry, and medical burden were risk factor covariates associated with response trajectory. As a contrast, logistic regression was used to assess the association between the same covariates and the probability of response (defined as HRSD-17 < or =10 and 50% reduction from baseline). In each study, there were 2 response trajectories with similar course, but with different speed. We classified the trajectories as "rapid response" and "slower response." Baseline HRSD-17 score was a significant predictor of response trajectory, with higher initial score related to slower response trajectory. Higher self-esteem was associated with more rapid response trajectory. In the logistic regression analysis, in two of the studies, higher baseline HRSD-17 score was a significant risk factor for nonresponse. In the study without psychotherapy, higher self-esteem was associated with responding to treatment. Thus, trajectory analysis can identify different trajectories of responders and determine psychosocial and clinical variables associated with response trajectory in the acute treatment of geriatric depression. Further study focusing on risk factors associated with slower response may help optimize treatment in elderly patients who do not respond quickly to first-line therapies.

Age Factors↗

PubMed2004

Prevalence of cognitive disorders differs as a function of age in HIV virus infection.

OBJECTIVES: Ten per cent of all new cases of AIDS in the United States are in persons older than 50 years. This is particularly problematical in the case of the neuropsychiatric consequences of HIV, because there are neuropsychiatric disorders which become common in older individuals in the absence of HIV. The purpose of this report is to describe the prevalence and incidence of cognitive impairment in HIV-infected individuals enrolled in a community-based study. DESIGN: The study consisted of community-based, sentinel survey physician referrals of HIV-infected patients, with volunteer recruitment of risk-appropriate seronegative controls. One-year longitudinal follow-up study. METHODS: Detailed neuropsychiatric evaluations were performed at study entry and after one year. A brief, interim visit tracked incident change. Each subject's neuropsychological test performance was classified as normal, demented, or cognitive impairment (not demented). RESULTS: The prevalence of cognitive disorder among HIV-positive individuals over 50 years was significantly greater than in individuals younger than 50 years. Among older participants, dementia was the more common classification (23%), whereas among younger participants, a milder form of cognitive impairment was more prevalent (22%). Alcohol abuse/dependence was a significant risk factor for a disorder, whereas greater education was a protective factor. The one-year incidence of disorder in the sample overall was low (7.3%), and age was not a significant risk factor. However, HIV viral load at study entry was significantly higher among those participants who had developed cognitive impairment one year later. CONCLUSION: Age is a significant risk modifier for prevalent neuropsychological disorder.

Activities of Daily Living↗

PubMed2004

Regional brain activation during concurrent implicit and explicit sequence learning.

We used event-related fMRI to identify the brain regions engaged during explicit and implicit sequence learning (ESL and ISL, respectively). Twenty-four subjects performed a concurrent ESL and ISL task. Behavior showed learning in both conditions. Prefrontal (PFC), striatal, anterior cingulate cortex (ACC) and visual regions (V1, V2 and V3) were engaged during both ESL and ISL. With ESL there was increased activity in the visual regions on the predictable (i.e. learned pattern) trials. With ISL, however, there was a relative decrease in activity in visual regions. The opposite patterns in the visual regions highlight the different effects of ESL and ISL. The learning process was distinguished from the result of learning, by fitting subjects' functional magnetic resonance imaging data to their learning curve. This analysis revealed more extensive PFC activity during ESL and caudal ACC activity specific for the result of learning analysis, when the expected response was violated. Our results suggest a relative dissociation of the brain regions engaged during ESL and ISL, whereby ESL and ISL can be viewed as partially distinct but overlapping parallel processes.

Adolescent↗

PubMed2004

The BOLD hemodynamic response in healthy aging.

Several previous studies have compared the blood oxygen level-dependent (BOLD) hemodynamic response (HDR) in healthy elderly subjects to the HDR in young subjects. Some studies have found a relative decreased amplitude in the elderly in the visual cortex, whereas other studies have found the elderly HDR amplitude in the visual cortex to be nearly identical to that in young subjects. A possible explanation for the different findings is that the peak voxel HDR is similar between the groups, but that the HDR in the group-averaged region-of-interest (ROI) is "washed out" by the inclusion of less significant voxels (due to a smaller extent of activation in the elderly) or by the inclusion of negative-peaking voxels. We tested this hypothesis using event-related functional magnetic resonance imaging (fMRI ). While undergoing fMRI, subjects performed a simple visual and motor task, pressing with their index fingers in response to visual presentation of the word tap. Data from 18 subjects, 8 young and 10 elderly, were analyzed. For each subject, a visual and a motor ROI was selected by choosing the most significant positive voxels within the anatomically defined ROI. This individual subject approach excluded both low-significance and negative-peaking voxels. Similar peaks were found for the elderly and the young subjects in both motor and visual regions and a more sustained BOLD response was found for the elderly in both regions. Additionally, as predicted, a greater percentage of voxels with a negative HDR was found for the elderly in the visual region; this finding was also replicated in our reanalysis of an independent fMRI and aging study from the fMRI Data Center. Functional neuroimaging observations of negative HDRs in visual areas have been interpreted as the effect of unconstrained processing during rest. Our results suggest that the elderly may have more unconstrained visual processing during the rest condition in the scanner. The observation that the group differences in the BOLD response are sensitive to voxel selection (e.g., inclusion of low-significance and/or negative voxels) underscores the importance of ROI selection criteria in the interpretation of fMRI studies using elderly populations.

Adult↗

PubMedDate not supplied

Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype.

OBJECTIVE: Psychotic symptoms occur in 30%-60% of individuals with Alzheimer disease (AD) with psychosis (AD+P). AD+P identifies a distinct AD phenotype, with increased severity of cognitive impairment and a more rapid cognitive decline. Using factor and cluster analysis, we previously proposed two subtypes of patients with AD+P, one characterized by misidentifications and hallucinations (Misidentification), the other by persecutory delusions (Paranoid). We hypothesized that these two groups differed in their patterns of cognitive impairment, compared with AD subjects without psychosis. METHODS: Subjects (N=119) with possible or probable AD were assessed with a comprehensive neuropsychological test battery at the time of initial presentation. Psychotic symptoms were ascertained with the CERAD Behavioral Rating Scale. Cognitive test scores were compared among groups by use of general linear-regression models, with age, education, and duration of illness entered as covariates. All results were corrected for multiple comparisons. RESULTS: The Misidentification group was significantly more impaired than the Non-Psychotic group on tests of verbal fluency and visuospatial function. The Paranoid group did not differ from the Non-Psychotic group on any test. CONCLUSIONS: These results support the identification of the Misidentification and Paranoid groups as distinct subgroups of AD+P. The ability to detect meaningful biologic associations of AD+P in future studies would be enhanced by separate analysis of the Misidentification and Paranoid phenotypes.

Aged↗