Biomedical subjects

Christian Habeck

Publications and source records attributed to Christian Habeck.

10 recordsLinked to original sources

PubMed2006

Imaging markers of mild cognitive impairment: multivariate analysis of CBF SPECT.

This study aimed to investigate cross-sectional and longitudinal changes of regional cerebral blood flow (rCBF) in preclinical dementia using single photon emission computed tomography (SPECT). SPECT and cognitive function were investigated in 39 mild cognitive impairment (MCI) subjects and 20 age-matched controls. All subjects were followed longitudinally 19 months on average, 16 MCI subjects progressed to Alzheimer's disease (AD), who were retrospectively defined as progressive mild cognitive impairment (PMCI) at baseline and 23 MCI subjects remained stable and were defined as stable mild cognitive impairment (SMCI) at baseline. SPECT was performed both at the initial investigation and at follow-up. Image data were analyzed using multivariate analysis, SPM and volume of interest (VOI)-based analysis. Significant covariate patterns were derived, which differentiate among PMCI, SMCI and controls at baseline as well as describe the longitudinal progression of PMCI. The combined SPECT and neuropsychology increased the diagnostic accuracy of PMCI at baseline. SPECT and neuropsychological testing can be used objectively for both baseline diagnosis and to monitor changes in brain function during very early AD.

Aged↗

PubMed2006

Structural MRI covariance patterns associated with normal aging and neuropsychological functioning.

Structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study used a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of the age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Eighty-four young (mean age=24.0) and 29 older (mean age=73.1) participants were scanned with a 1.5T MRI machine and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate technique, based on the subprofile scaling model, was used to capture sources of between- and within-group variation to produce a linear combination of principal components that represented a "pattern" or "network" that best discriminated between the two age groups. Univariate analyses were also conducted with statistical parametric maps. Grey and white matter covariance patterns were identified that reliably discriminated between the groups with greater than 0.90 sensitivity and specificity. The identified patterns were similar for the univariate and multivariate techniques, and involved widespread regions of the cortex and subcortex. Age and the expression of both patterns were significantly associated with performance on tests of attention, language, memory, and executive functioning. The results suggest that identifiable networks of grey and white matter regions systematically decline with age and that pattern expression is linked to age-related cognitive decline.

Adult↗

PubMed2006

An event-related fMRI study of the neural networks underlying repetition suppression and reaction time priming in implicit visual memory.

Unfamiliar line drawings were presented to subjects three times during BOLD fMRI scanning. A set of brain areas was detected in which the effect of stimulus repetition on the evoked fMRI response depended on whether or not the drawing could be conceived as a coherent three-dimensional structure. Differential repetition effects were found in the neural response to drawings of both structurally possible and impossible objects. This differential effect of repetition was related to the amount of reaction time priming on the concurrent task involving decisions about three-dimensional structure in the possible but not in the impossible objects. These results point to different neurophysiological processing mechanisms for structurally possible and impossible images and demonstrate neural plasticity that predicts behavioral priming for structurally possible images.

Adolescent↗

PubMed2005

Brain networks associated with cognitive reserve in healthy young and old adults.

In order to understand the brain networks that mediate cognitive reserve, we explored the relationship between subjects' network expression during the performance of a memory test and an index of cognitive reserve. Using H2(15)O positron emission tomography, we imaged 17 healthy older subjects and 20 young adults while they performed a serial recognition memory task for nonsense shapes under two conditions: low demand, with a unique shape presented in each study trial; and titrated demand, with a study list size adjusted so that each subject recognized shapes at 75% accuracy. A factor score that summarized years of education, and scores on the NART and the WAIS-R Vocabulary subtest was used as an index of cognitive reserve. The scaled subprofile model was used to identify a set of functionally connected regions (or topography) that changed in expression across the two task conditions and was differentially expressed by the young and elderly subjects. The regions most active in this topography consisted of right hippocampus, posterior insula, thalamus, and right and left operculum; we found concomitant deactivation in right lingual gyrus, inferior parietal lobe and association cortex, left posterior cingulate, and right and left calcarine cortex. Young subjects with higher cognitive reserve showed increased expression of the topography across the two task conditions. Because this topography, which is responsive to increased task demands, was differentially expressed as a function of reserve level, it may represent a neural manifestation of innate or acquired reserve. In contrast, older subjects with higher cognitive reserve showed decreased expression of the topography across tasks. This suggests some functional reorganization of the network used by the young subjects. Thus, for the old subjects this topography may represent an altered, compensatory network that is used to maintain function in the face of age-related physiological changes.

Adult↗

PubMed2005

A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.

In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particularly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of awareness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that exhibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in studies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expression as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about functional connectivity based solely on experimental design variables. In particular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial information about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical methods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H(2)15O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.

Adult↗

PubMed2004

An event-related fMRI study of the neural networks underlying the encoding, maintenance, and retrieval phase in a delayed-match-to-sample task.

Memory loads exceeding the limited capacity of working memory (WM) have been shown to expand the prefrontal areas that participate in WM and have revealed substantial individual differences in performance. We used a delayed-match-to-sample (DMS) task in an event-related fMRI study to map the full extent of the expanded regional activations associated with supracapacity loads. A 6-letter study array was compared to arrays of 1 and 3 letters. The task comprised separate encoding, retention, and retrieval fMRI epochs. A brain-wide spatial covariance analysis was applied to the data of all task epochs to identify patterns of correlated regional activations whose expression increased monotonically across 3 memory-load levels on a subject-by-subject basis. Such load-related activation patterns were in all task phases. Of greatest interest is the activation pattern that was obtained during the maintenance phase: increasing activation with memory load was found not only in the lateral PFC (BA 9,44) but also in the parietal lobe (BA 7,40), anterior cingulate (BA 32), and cerebellum. Decreasing activation was found in the occipito-temporal lobe (BA 19,39) as well as the medial prefrontal cortex (BA 9,10). Subject increases in pattern expression from 1 to 6 items were positively correlated with the corresponding reaction time increases (p<0.05) and negatively correlated with NARTIQ (p<0.05), indicating that people who were faster in their responses and had higher NARTIQ had to increase their subject expression of the memory-load-related activation pattern less and were more efficient at the cognitive task. Our method thus not only reproduced findings of other WM studies but also addressed the issue of interactions between lateral PFC and other parts of the brain during the task, for the retention of the to-be-remembered information. The load-related activation patterns from encoding and retrieval phase and their relationship to behavior are also discussed.

Adult↗

PubMed2004

Identification and differential vulnerability of a neural network in sleep deprivation.

The study aimed to identify task-related brain activation networks whose change in expression exhibits subject differences as a function of differential susceptibility to sleep deprivation. Brain activity during a non-verbal recognition memory task was investigated in an event-related functional MRI paradigm both prior to and after 48 h of sleep deprivation. Nineteen healthy subjects participated. Regional covariance analysis was applied to data. An activation network pattern was identified whose expression decreased from pre- to post-sleep deprivation in 15 out 19 subjects (P < 0.05). Differential decrease in expression correlated with worsening performance in recognition accuracy (P < 0.05). Sites of de-activation were found in the posterior cerebellum, right fusiform gyrus and precuneus, and left lingual and inferior temporal gyri; increased activation was found in the bilateral insula, claustrum and right putamen. A network whose expression decreased after sleep deprivation and correlated with memory performance was identified. We conclude that this activation network plays a role in cognitive function during sleep deprivation.

Adaptation, Physiological↗

PubMed2004

An event-related fMRI study of the neurobehavioral impact of sleep deprivation on performance of a delayed-match-to-sample task.

Eighteen subjects (ages 18-35) underwent event-related functional magnetic resonance imaging (efMRI) while performing a delayed-match-to-sample (DMS) task before and immediately after 48 h of sustained wakefulness. The DMS trial events were: a 3-s study period of either a one-, three-, or six-letter visual array; a 7-s retention interval; and a 3-s probe period, where a button press indicated whether the probe letter was in the study array. Ordinal Trend Canonical Variates Analysis (OrT CVA) was applied to the data from the probe period for trials with six-letter study lists prior to and immediately following sleep deprivation to find an activation pattern whose expression decreased with sleep deprivation in as many subjects as possible, while being present in both conditions. The first principal component of the OrT analysis identified a covariance pattern whose expression decreased as a function of sleep deprivation in 17 of 18 subjects (p<0.001). While overall expression of the pattern showed a systematic decrease with sleep deprivation, the brain regions that make up the pattern show covarying increases and decreases in activation. Regions that decreased their activation were noted in the parietal (BA 7 and 40), temporal (BA 37, 38 and 39) and occipital (BA 18 and 19) lobes; regions that increased their activation were noted in the cerebellum, basal ganglia, thalamus and the anterior cingulate gyrus (BA 32). The reduction in pattern expression with sleep deprivation for each subject was related to the change in performance on the DMS task. Subject decreases in pattern expression were correlated with reductions in recognition accuracy (p<0.05), increased intra-individual variability in reaction time (p<0.005) and increased lapsing (p<0.005).

Adult↗

PubMed2003

Relation of cognitive reserve and task performance to expression of regional covariance networks in an event-related fMRI study of nonverbal memory.

Cognitive reserve (CR) has been established as a mechanism that can explain individual differences in the clinical manifestation of neural changes associated with aging or neurodegenerative diseases. CR may represent individual differences in how tasks are processed (i.e., differences in the component processes), or in the underlying neural circuitry (of the component processes). CR may be a function of innate differences or differential life experiences. To investigate to what extent CR can account for individual differences in brain activation and task performance, we used fMRI to image healthy young individuals while performing a nonverbal memory task. We used IQ estimates as a proxy for CR. During both study and test phase of the task, we identified regional covariance patterns whose change in subject expression across two task conditions correlated with performance and CR. Common brain regions in both activation patterns were suggestive of a brain network previously found to underlie overt and covert shifts of spatial attention. After partialing out the influence of task performance variables, this network still showed an association with the CR, i.e., there were reserve-related physiological differences that presumably would persist were there no subject differences in task performance. This suggests that this network may represent a neural correlate of CR.

Adult↗

PubMedDate not supplied

Altered PET functional brain responses in cognitively intact elderly persons at risk for Alzheimer disease (carriers of the epsilon4 allele).

OBJECTIVE: Few previous studies have investigated the association between APOE genotype and brain activation during performance of cognitive tasks in healthy middle-aged and elderly subjects, and the results have been mixed. The authors investigated APOE-mediated differential brain activation in a group of healthy elderly subjects. METHODS: Using H215O positron emission tomography (PET), they imaged 32 healthy subjects (26 non-epsilon4 carriers and 6 epsilon4 carriers) performing a serial shape-recognition memory task under two conditions: Simple Demand (SD), in which one shape was presented in each study trial, and Titrated Demand (TD), in which study list length was adjusted so that each subject recognized words at approximately 75% accuracy. Multiple-regression analyses were performed, with the "activation" difference (TD-SD PET counts) as the dependent variable and the APOE genotype (presence versus absence of the epsilon4 allele) as the independent variable. RESULTS: Compared with non-carriers, epsilon4 carriers exhibited significantly decreased TD-SD activation differences in the left superior temporal, right superior frontal, left postcental, left precuneus, and posterior cingulate gyrus because epsilon4 carriers (versus non-carriers) showed increased activation during the SD and decreased activation during the TD condition. CONCLUSION: Patterns of brain activation during a nonverbal memory task differed as a function of APOE genotype and, therefore, of genetic risk for Alzheimer disease (AD). Differences in activation were not a reflection of task difficulty, but indicate memory-related altered cognitive processing. Brain regions with decreased activation in the epsilon4 subjects may result from subclinical incipient AD pathology and/or APOE-related neurophysiologic heterogeneity.

Aged↗