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Biomedical subjects

Randy L Buckner

Publications and source records attributed to Randy L Buckner.

14 recordsLinked to original sources
PubMed2026

Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders (SSDs) produce severe symptoms, disability, and premature mortality, but only partially effective symptomatic treatments exist. Treatment development is impeded by lack of insight into disease mechanisms or objective biomarkers for clinical trials. Advances in genetics and neurobiology have converged on strong pathogenic hypotheses for SSDs centered on synapse dysfunction and excessive pruning, pathogenic processes that may produce measurable proteomic evidence in cerebrospinal fluid (CSF). Leveraging design precedents from successful fluid biomarkers discovery for Alzheimer's disease, we undertook a pilot study to test the feasibility of repeated CSF and blood samples collection from individuals with SSDs. Here we report on successful implementation of longitudinal bio-behavioral phenotyping in SSDs and establishment of a repository to permit broad sample and data sharing. STUDY DESIGN: The Schizophrenia Spectrum Biomarkers Consortium (SSBC) study principles included longitudinal study design, paired CSF and plasma collection associated with robust phenotypic characterization, at 3 academic sites and the establishment of a biorepository. Participants underwent clinical and cognitive assessments, neuroimaging, blood draws, and CSF collection via lumbar puncture (LP) every 6 months. STUDY RESULTS: SSBC successfully enrolled 48 SSD and 41 Healthy Controls with a 73% longitudinal retention. Clinical, cognitive, and neuroimaging results were consistent across sites and with existing studies. Study procedures were well tolerated, and almost all LPs (99%) resulted in either no or minor headache/backache that resolved without medical interventions. CONCLUSIONS: The pilot SSBC study demonstrates that a multi-site, longitudinal study with repeat CSF collection is feasible, with excellent participant acceptability and retention.

Humans↗
PubMed2003

Functional-anatomic correlates of sustained and transient processing components engaged during controlled retrieval.

Controlled processing is central to episodic memory retrieval. In the present study, neural correlates of sustained, as well as transient, processing components were explored during controlled retrieval using a mixed blocked event-related functional magnetic resonance imaging paradigm. Results from 29 participants suggest that certain regions in prefrontal cortex, including anterior left inferior prefrontal cortex near Brodmann's Area (BA) 45/47 and more posterior and dorsal left prefrontal cortex near BA 44, increase activity on a trial-by-trial basis when high levels of control are required during retrieval. Providing direct evidence for control processes that participate on an ongoing basis, right frontal-polar cortex was strongly associated with a sustained temporal profile during high control retrieval conditions, as were several additional posterior regions, including those within left parietal cortex. These results provide evidence for functional dissociation within prefrontal cortex. Frontal-polar regions near BA 10 associate with temporally extended control processes that may underlie an attentional set, or retrieval mode, during controlled retrieval, whereas more posterior prefrontal regions associate with individual retrieval attempts. In particular, right frontal-polar cortex involvement in sustained processes reconciles a number of disparate findings that have arisen when contrasting blocked-trial paradigms with event-related paradigms.

Adolescent↗
PubMed2003

Functional dissociation among components of remembering: control, perceived oldness, and content.

Remembering is the ability to bring back to mind episodes from one's past and is presumably accomplished by multiple, interdependent processes. In the present functional magnetic resonance imaging study, neural correlates of three hypothesized components of remembering were explored, including those associated with control, perceived oldness, and retrieved content. Levels of each component were separately manipulated by varying study procedures and sorting trials by subject response. Results suggest that specific regions in the left prefrontal cortex, including anterior-ventral Brodmann's Area (BA) 45/47 and more dorsal BA 44, increase activity when high levels of control are required but do not necessarily modulate on the basis of perceived oldness. Parietal and frontal regions, particularly the left parietal cortex near BA 40/39, associate with the perception that information is old and generalize across levels of control and retrieved content. Activity in the parietal cortex correlated with perceived oldness even when judgments were in error. The inferior temporal cortex near BA 19/37 associated differentially with retrieval of visual object content. Within the ventral visual processing stream, content-based modulation was specific to late object-responsive regions, suggesting an efficient retrieval process that spares areas that process more primitive retinotopically mapped visual features. Taken collectively, the results identify neural correlates of distinct components of remembering and provide evidence for a functional dissociation. Frontal regions may contribute to control processes that interact with different posterior regions that contribute a signal that information is old and support the contents of retrieval.

Acoustic Stimulation↗
PubMed2003

Spelling via semantics and phonology: exploring the effects of age, Alzheimer's disease, and primary semantic impairment.

Spelling performance across a common set of stimuli was examined in young adults, healthy older adults, individuals with early stage dementia of the Alzheimer's type (DAT), and four individuals with a primary semantic impairment (PSI). The stimuli included homophones and low-frequency sound-to-spelling consistent (i.e. words with more predictable spellings) and inconsistent words (i.e. words with less predictable spellings). The results indicate that when spelling homophonic words (spelling/pleIn/ as plane versus plain), younger adults and to a greater extent individuals with PSI placed relatively more emphasis on phonological information (i.e. spell the word based on sound-to-spelling principles) whereas healthy older adults and individuals with DAT placed relatively more emphasis on semantic information (i.e. spell the word based on the dominant usage). For non-homophonic words, large consistency effects (spelling plaid as plad) were observed for both individuals with DAT and individuals with PSI. It is proposed that the decrease in accuracy for inconsistent words has different bases in DAT and PSI. We propose that deficits in attentional control (i.e. selection) underlie performance in DAT whereas disruption of semantic representations underlies performance in PSI.

Acoustic Stimulation↗
PubMed2003

Does the right hemisphere take over after damage to Broca's area? the Barlow case of 1877 and its history.

In 1877 Thomas Barlow, a London physician, published a remarkable case of functional recovery of speech following brain damage. It involved a 10-year-old boy who had lost his speech, regained it, and lost it again before he died from a disorder that affected his heart and produced embolisms that subsequently affected other organs, including his brain. Examination of the boy's brain revealed two focal regions of softening; one that affected Broca's area and the left facial-motor area, and another, which occurred weeks later, in the homologous regions of the right hemisphere. Although Barlow was most concerned with motor deficits, others at the turn of the century began to cite this case as strong evidence that the corresponding region of the right hemisphere can take over speech functions for Broca's area on the left. Whether this case really provides good support for functional takeover or vicariation theory is critically evaluated in the light of contemporary research, including PET scan studies involving damage to Broca's speech region.

Aphasia, Broca↗
PubMed2003

Neural correlates of incongruous visual information. An event-related fMRI study.

Incongruous information is better remembered than ordinary information. This result has been attributed both to semantic incongruity and surprise. To determine the contribution of each factor, we performed a functional magnetic resonance imaging study in which participants viewed pictures depicting ordinary and incongruous objects (e.g., head of a wrench fused onto a sheep body). To maximize surprise we administered novel incongruent pictures infrequently in an initial scan. (This scan also included infrequent color-inverted pictures as a control for frequency.) To obtain a pure measure of the effect of incongruity we conducted a second scan in which participants viewed equal numbers of ordinary and incongruous pictures. Signal increases were greater for incongruous versus ordinary and oddball stimuli throughout the ventral and dorsal visual pathways, and in prefrontal cortex bilaterally. Signal decreases were larger for incongruous than for ordinary stimuli bilaterally in lateral parietal regions. A subset of regions near the right frontal operculum and extending laterally responded only to, or more strongly to, infrequent incongruous pictures. A second, purely behavioral, experiment involving a separate group of participants demonstrated that incongruous pictures were better recognized than ordinary pictures. We interpret our results as suggesting that, although correlates of a surprise response can be observed, better memory for incongruous visual information is attributable mainly to more processing and, consequently, better encoding.

Adult↗
PubMed2003

Mixed blocked/event-related designs separate transient and sustained activity in fMRI.

Recent functional magnetic resonance imaging (fMRI) studies using mixed blocked/event-related designs have shown activity consistent with separable sustained task-related processes and transient trial-related processes. In the mixed design, control blocks are intermixed with task blocks, during which trials are presented at varying intervals. Two studies were conducted to assess the ability of this design to detect and dissociate sustained task-related from transient trial-related activity. Analyses on both simulated and empirical data were performed by using the general linear model with a shape assumed for sustained effects, but not transient effects. In the first study, simulated data were produced with sustained time courses, transient time courses, and the sum of both together. Analyses of these data showed appropriate parsing of sustained and transient activity in all three cases. For the empirical fMRI experiment, counterphase-flickering checkerboard stimuli were constructed to produce sustained, transient, and combined sustained and transient responses in visual cortex. As with the simulation, appropriate parsing of sustained and transient activity was seen in all three cases; i.e., sustained stimuli produced sustained time courses and transient stimuli produced transient time courses. Combined stimuli produced both transient and sustained time courses. Critically, transient stimuli alone did not produce spurious positive sustained responses; sustained stimuli alone produced negligible spurious transient time courses. The results of these two studies along with supplemental simulations provide strong evidence that mixed designs are an effective tool for separating transient, trial-related activity from sustained activity in fMRI experiments. Mixed designs can allow researchers a means to examine brain activity associated with sustained processes, potentially related to task-level control signals.

Attention↗
PubMed2003

Imaging of Alzheimer's disease.

Imaging is widely used in the evaluation of Alzheimer's disease (AD). In addition to imaging's traditional role of aiding in the exclusion of diseases that may be confused with AD, structural and functional imaging are being explored for potential use in the early detection of AD and as surrogate markers of treatment outcome. Volumetric measurements of the hippocampal and entorhinal regions using modern magnetic resonance imaging (MRI) and computed tomography are most widely studied in the discrimination of AD from nondemented aging and other dementias. Other imaging modalities include positron emission tomography and single-photon-emission computed tomography, which evaluate global and regional disturbances of blood flow and metabolism, and proton spectroscopy, which assesses neuronal degeneration and loss as marked by the presence of abnormal metabolites. Diffusion tensor and functional MRI, which examine white matter changes and brain-behavior relationships, are more recent techniques that contribute to the burgeoning application of imaging techniques to dementing illnesses and are notably improving our understanding of the pathophysiology of AD.

Alzheimer Disease↗
PubMed2002

Common prefrontal regions coactivate with dissociable posterior regions during controlled semantic and phonological tasks.

One of the most ubiquitous findings in functional neuroimaging research is activation of left inferior prefrontal cortex (LIPC) during tasks requiring controlled semantic retrieval. Here we show that LIPC participates in the controlled retrieval of nonsemantic representations as well as semantic representations. Results also demonstrate that LIPC coactivates with dissociable posterior regions depending on the information retrieved: activating with left temporal cortex during the controlled retrieval of semantics and with left posterior frontal and parietal cortex during the controlled retrieval of phonology. Correlation of performance to LIPC activation suggests a processing role associated with mapping relatively ambiguous stimulus-to-representation relationships during both semantic and phonological tasks. These findings suggest that LIPC participates in controlled processing across multiple information domains collaborating with dissociable posterior regions depending upon the kind of information retrieved.

Adult↗
PubMed2002

Under-recruitment and nonselective recruitment: dissociable neural mechanisms associated with aging.

Frontal contributions to cognitive decline in aging were explored using functional MRI. Frontal regions active in younger adults during self-initiated (intentional) memory encoding were under-recruited in older adults. Older adults showed less activity in anterior-ventral regions associated with controlled use of semantic information. Under-recruitment was reversed by requiring semantic elaboration suggesting it stemmed from difficulty in spontaneous recruitment of available frontal resources. In addition, older adults recruited multiple frontal regions in a nonselective manner for both verbal and nonverbal materials. Lack of selectivity was not reversed during semantically directed encoding even when under-recruitment was diminished. These findings suggest two separate forms of age-associated change in frontal cortex: under-recruitment and nonselective recruitment. The former is reversible and potentially amenable to cognitive training; the latter may reflect a less malleable change associated with cognitive decline in advanced aging.

Adolescent↗
PubMed2002

The feasibility of a common stereotactic space for children and adults in fMRI studies of development.

The question of whether pediatric and adult neuroimaging data can be analyzed in a common stereotactic space is a critical issue for developmental neuroscience. Two studies were performed to address this question. In Study 1, high-resolution structural MR brain images of 20 children (7-8 years of age) and 20 young adults (18-30 years of age) were transformed to a common space. Overall brain shape was assessed by tracing the outer boundaries of the brains in three orientations, and more local anatomy was assessed by analysis of portions of 10 selected sulci. Small, but consistent, differences in location and variability were observed in specific locations of the sulcal tracings and outer-boundary sections. In Study 2, a computer simulation was used to assess the extent to which the small anatomical differences observed in Study 1 would produce spurious effects in functional imaging data. Results indicate that, assuming a functional resolution of 5 mm in images averaged across subjects, anatomical differences in either variability or location between children and adults of the magnitude obperved in Study 1 would not negatively affect functional image comparisons. We conclude that atlas-transformed brain morphology is relatively consistent between 7- and 8-year-old children and adults at a resolution appropriate to current functional imaging and that the small anatomical differences present do not limit the usefulness of comparing child and adult functional images within a common stereotactic space.

Adolescent↗