Randy L. Buckner

YNIMG Journal 2023 Journal Article

Brain morphometry in older adults with and without dementia using extremely rapid structural scans

• Maxwell L. Elliott
• Lindsay C. Hanford
• Aya Hamadeh
• Tom Hilbert
• Tobias Kober
• Bradford C. Dickerson
• Ross W. Mair
• Mark C. Eldaief

T1-weighted structural MRI is widely used to measure brain morphometry (e.g., cortical thickness and subcortical volumes). Accelerated scans as fast as one minute or less are now available but it is unclear if they are adequate for quantitative morphometry. Here we compared the measurement properties of a widely adopted 1.0 mm resolution scan from the Alzheimer's Disease Neuroimaging Initiative (ADNI = 5'12'') with two variants of highly accelerated 1.0 mm scans (compressed-sensing, CSx6 = 1'12''; and wave-controlled aliasing in parallel imaging, WAVEx9 = 1'09'') in a test-retest study of 37 older adults aged 54 to 86 (including 19 individuals diagnosed with a neurodegenerative dementia). Rapid scans produced highly reliable morphometric measures that largely matched the quality of morphometrics derived from the ADNI scan. Regions of lower reliability and relative divergence between ADNI and rapid scan alternatives tended to occur in midline regions and regions with susceptibility-induced artifacts. Critically, the rapid scans yielded morphometric measures similar to the ADNI scan in regions of high atrophy. The results converge to suggest that, for many current uses, extremely rapid scans can replace longer scans. As a final test, we explored the possibility of a 0'49'' 1.2 mm CSx6 structural scan, which also showed promise. Rapid structural scans may benefit MRI studies by shortening the scan session and reducing cost, minimizing opportunity for movement, creating room for additional scan sequences, and allowing for the repetition of structural scans to increase precision of the estimates.

YNIMG Journal 2021 Journal Article

Characterizing cerebral hemodynamics across the adult lifespan with arterial spin labeling MRI data from the Human Connectome Project-Aging

• Meher R. Juttukonda
• Binyin Li
• Randa Almaktoum
• Kimberly A. Stephens
• Kathryn M. Yochim
• Essa Yacoub
• Randy L. Buckner
• David H. Salat

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) has become a popular approach for studying cerebral hemodynamics in a range of disorders and has recently been included as part of the Human Connectome Project-Aging (HCP-A). Due to the high spatial resolution and multiple post-labeling delays, ASL data from HCP-A holds promise for localization of hemodynamic signals not only in gray matter but also in white matter. However, gleaning information about white matter hemodynamics with ASL is challenging due in part to longer blood arrival times in white matter compared to gray matter. In this work, we present an analytical approach for deriving measures of cerebral blood flow (CBF) and arterial transit times (ATT) from the ASL data from HCP-A and report on gray and white matter hemodynamics in a large cohort (n = 234) of typically aging adults (age 36-90 years). Pseudo-continuous ASL data were acquired with labeling duration = 1500 ms and five post-labeling delays = 200 ms, 700 ms, 1200, 1700 ms, and 2200 ms. ATT values were first calculated on a voxel-wise basis through normalized cross-correlation analysis of the acquired signal time course in that voxel and an expected time course based on an acquisition-specific Bloch simulation. CBF values were calculated using a two-compartment model and with age-appropriate blood water longitudinal relaxation times. Using this approach, we found that white matter CBF reduces (ρ = 0.39) and white matter ATT elongates (ρ = 0.42) with increasing age (p < 0.001). In addition, CBF is lower and ATTs are longer in white matter compared to gray matter across the adult lifespan (Wilcoxon signed-rank tests; p < 0.001). We also found sex differences with females exhibiting shorter white matter ATTs than males, independently of age (Wilcoxon rank-sum test; p < 0.001). Finally, we have shown that CBF and ATT values are spatially heterogeneous, with significant differences in cortical versus subcortical gray matter and juxtacortical versus periventricular white matter. These results serve as a characterization of normative physiology across the human lifespan against which hemodynamic impairment due to cerebrovascular or neurodegenerative diseases could be compared in future studies.

YNIMG Journal 2019 Journal Article

The Lifespan Human Connectome Project in Aging: An overview

• Susan Y. Bookheimer
• David H. Salat
• Melissa Terpstra
• Beau M. Ances
• Deanna M. Barch
• Randy L. Buckner
• Gregory C. Burgess
• Sandra W. Curtiss

The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al. , 2018), and the image acquisition protocol common to both studies (Harms et al. , 2018).

YNIMG Journal 2018 Journal Article

Extending the Human Connectome Project across ages: Imaging protocols for the Lifespan Development and Aging projects

• Michael P. Harms
• Leah H. Somerville
• Beau M. Ances
• Jesper Andersson
• Deanna M. Barch
• Matteo Bastiani
• Susan Y. Bookheimer
• Timothy B. Brown

The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5–21), and HCP-A is enrolling 1200+ healthy adults (ages 36–100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22–35), but some imaging-related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.

YNIMG Journal 2018 Journal Article

The Lifespan Human Connectome Project in Development: A large-scale study of brain connectivity development in 5–21 year olds

• Leah H. Somerville
• Susan Y. Bookheimer
• Randy L. Buckner
• Gregory C. Burgess
• Sandra W. Curtiss
• Mirella Dapretto
• Jennifer Stine Elam
• Michael S. Gaffrey

Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300 + healthy human participants, ages 5–21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9–17 years). Brain imaging sessions are acquired on a 3 T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.

YNIMG Journal 2017 Journal Article

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide

• Paul M. Thompson
• Ole A. Andreassen
• Alejandro Arias-Vasquez
• Carrie E. Bearden
• Premika S. Boedhoe
• Rachel M. Brouwer
• Randy L. Buckner
• Jan K. Buitelaar

In this review, we discuss recent work by the ENIGMA Consortium (http: //enigma. ini. usc. edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others 1 1 Abbreviations: ADNI, Alzheimer's Disease Neuroimaging Initiative (http: //www. adni-info. org); CHARGE, the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (http: //www. chargeconsortium. com); IMAGEN, IMAging GENetics Consortium (http: //www. imagen-europe. com). , ENIGMA's genomic screens – now numbering over 30, 000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

YNIMG Journal 2016 Journal Article

MGH–USC Human Connectome Project datasets with ultra-high b-value diffusion MRI

• Qiuyun Fan
• Thomas Witzel
• Aapo Nummenmaa
• Koene R.A. Van Dijk
• John D. Van Horn
• Michelle K. Drews
• Leah H. Somerville
• Margaret A. Sheridan

The MGH–USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH–USC Adult Diffusion Dataset (N =35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU–Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH–Harvard–USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH–USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography.

YNIMG Journal 2016 Journal Article

Prospective motion correction with volumetric navigators (vNavs) reduces the bias and variance in brain morphometry induced by subject motion

• M. Dylan Tisdall
• Martin Reuter
• Abid Qureshi
• Randy L. Buckner
• Bruce Fischl
• André J.W. van der Kouwe

Recent work has demonstrated that subject motion produces systematic biases in the metrics computed by widely used morphometry software packages, even when the motion is too small to produce noticeable image artifacts. In the common situation where the control population exhibits different behaviors in the scanner when compared to the experimental population, these systematic measurement biases may produce significant confounds for between-group analyses, leading to erroneous conclusions about group differences. While previous work has shown that prospective motion correction can improve perceived image quality, here we demonstrate that, in healthy subjects performing a variety of directed motions, the use of the volumetric navigator (vNav) prospective motion correction system significantly reduces the motion-induced bias and variance in morphometry.

YNIMG Journal 2015 Journal Article

Gray matter myelination of 1555 human brains using partial volume corrected MRI images

• Rebecca Shafee
• Randy L. Buckner
• Bruce Fischl

The myelin content of the cortex changes over the human lifetime and aberrant cortical myelination is associated with diseases such as schizophrenia and multiple sclerosis. Recently magnetic resonance imaging (MRI) techniques have shown potential in differentiating between myeloarchitectonically distinct cortical regions in vivo. Here we introduce a new algorithm for correcting partial volume effects present in mm-scale MRI images which was used to investigate the myelination pattern of the cerebral cortex in 1555 clinically normal subjects using the ratio of T1-weighted (T1w) and T2-weighted (T2w) MRI images. A significant linear cross-sectional age increase in T1w/T2w estimated myelin was detected across an 18 to 35year age span (highest value of ~ 1%/year compared to mean T1w/T2w myelin value at 18 years). The cortex was divided at mid-thickness and the value of T1w/T2w myelin calculated for the inner and outer layers separately. The increase in T1w/T2w estimated myelin occurs predominantly in the inner layer for most cortical regions. The ratio of the inner and outer layer T1w/T2w myelin was further validated using high-resolution in vivo MRI scans and also a high-resolution MRI scan of a postmortem brain. Additionally, the relationships between cortical thickness, curvature and T1w/T2w estimated myelin were found to be significant, although the relationships varied across the cortex. We discuss these observations as well as limitations of using the T1w/T2w ratio as an estimate of cortical myelin.

YNIMG Journal 2015 Journal Article

Head motion during MRI acquisition reduces gray matter volume and thickness estimates

• Martin Reuter
• M. Dylan Tisdall
• Abid Qureshi
• Randy L. Buckner
• André J.W. van der Kouwe
• Bruce Fischl

Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal development, disease, and the effects of disease-modifying therapies. However, motion during image acquisition introduces image artifacts that, in turn, affect derived markers. A systematic effect can be problematic since factors of interest like age, disease, and treatment are often correlated with both a structural change and the amount of head motion in the scanner, confounding the ability to distinguish biology from artifact. Here we evaluate the effect of head motion during image acquisition on morphometric estimates of structures in the human brain using several popular image analysis software packages (FreeSurfer 5. 3, VBM8 SPM, and FSL Siena 5. 0. 7). Within-session repeated T1-weighted MRIs were collected on 12 healthy volunteers while performing different motion tasks, including two still scans. We show that volume and thickness estimates of the cortical gray matter are biased by head motion with an average apparent volume loss of roughly 0. 7%/mm/min of subject motion. Effects vary across regions and remain significant after excluding scans that fail a rigorous quality check. In view of these results, the interpretation of reported morphometric effects of movement disorders or other conditions with increased motion tendency may need to be revisited: effects may be overestimated when not controlling for head motion. Furthermore, drug studies with hypnotic, sedative, tranquilizing, or neuromuscular-blocking substances may contain spurious “effects” of reduced atrophy or brain growth simply because they affect motion distinct from true effects of the disease or therapeutic process.

YNIMG Journal 2014 Journal Article

Borders, map clusters, and supra-areal organization in visual cortex

• Randy L. Buckner
• B.T. Thomas Yeo

V1 is a canonical cortical area with clearly delineated architectonic boundaries and a continuous topographic representation of the visual hemifield. It thus serves as a touchstone for understanding what new mapping methods can tell us about cortical organization. By parcellating human cortex using local gradients in functional connectivity, Wig et al. (2014--in this issue) detected the V1 border with V2. By contrast, previously-published clustering methods that focus on global similarity in connectivity reveal a supra-areal organization that emphasizes eccentricity bands spanning V1 and its neighboring extrastriate areas; i. e. in the latter analysis, the V1 border is not evident. Thus the focus on local connectivity gradients emphasizes qualitatively different features of cortical organization than are captured by global similarity measures. What is intriguing to consider is that each kind of information might be telling us something unique about cortical organization. Global similarity measures may be detecting map clusters and other supra-areal arrangements that reflect a fundamental level of organization.

YNIMG Journal 2014 Journal Article

Estimates of segregation and overlap of functional connectivity networks in the human cerebral cortex

• B.T. Thomas Yeo
• Fenna M. Krienen
• Michael W.L. Chee
• Randy L. Buckner

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP.

YNIMG Journal 2012 Journal Article

The influence of head motion on intrinsic functional connectivity MRI

• Koene R.A. Van Dijk
• Mert R. Sabuncu
• Randy L. Buckner

Functional connectivity MRI (fcMRI) has been widely applied to explore group and individual differences. A confounding factor is head motion. Children move more than adults, older adults more than younger adults, and patients more than controls. Head motion varies considerably among individuals within the same population. Here we explored the influence of head motion on fcMRI estimates. Mean head displacement, maximum head displacement, the number of micro movements (>0. 1mm), and head rotation were estimated in 1000 healthy, young adult subjects each scanned for two resting-state runs on matched 3T scanners. The majority of fcMRI variation across subjects was not linked to head motion. However, head motion had significant, systematic effects on fcMRI network measures. Head motion was associated with decreased functional coupling in the default and frontoparietal control networks — two networks characterized by coupling among distributed regions of association cortex. Other network measures increased with motion including estimates of local functional coupling and coupling between left and right motor regions — a region pair sometimes used as a control in studies to establish specificity. Comparisons between groups of individuals with subtly different levels of head motion yielded difference maps that could be mistaken for neuronal effects in other contexts. These effects are important to consider when interpreting variation between groups and across individuals.

YNIMG Journal 2012 Journal Article

The serendipitous discovery of the brain's default network

• Randy L. Buckner

One of the most unexpected findings by functional neuroimaging has been the discovery of the brain's default network — a set of brain regions that is spontaneously active during passive moments. The default network's discovery was a fortunate accident that occurred due to the inclusion of rest control conditions in early PET and functional MRI studies. At first, the network was ignored. Later, its presence was shunned as evidence of an experimental confound. Finally, it emerged as a mainstream target of focused study. Here, I describe a personal perspective of the default network's serendipitous discovery.

YNIMG Journal 2009 Journal Article

Predicting the location of entorhinal cortex from MRI

• Bruce Fischl
• Allison A. Stevens
• Niranjini Rajendran
• B.T. Thomas Yeo
• Douglas N. Greve
• Koen Van Leemput
• Jonathan R. Polimeni
• Sita Kakunoori

Entorhinal cortex (EC) is a medial temporal lobe area critical to memory formation and spatial navigation that is among the earliest parts of the brain affected by Alzheimer's disease (AD). Accurate localization of EC would thus greatly facilitate early detection and diagnosis of AD. In this study, we used ultra-high resolution ex vivo MRI to directly visualize the architectonic features that define EC rostrocaudally and mediolaterally, then applied surface-based registration techniques to quantify the variability of EC with respect to cortical geometry, and made predictions of its location on in vivo scans. The results indicate that EC can be localized quite accurately based on cortical folding patterns, within 3 mm in vivo, a significant step forward in our ability to detect the earliest effects of AD when clinical intervention is most likely to be effective.

YNIMG Journal 2007 Journal Article

Dissociable but inter-related systems of cognitive control and reward during decision making: Evidence from pupillometry and event-related fMRI

• Theodore D. Satterthwaite
• Leonard Green
• Joel Myerson
• Jamie Parker
• Mohana Ramaratnam
• Randy L. Buckner

Decision making involves the allocation of cognitive resources in response to expectations and feedback. Here we explored how frontal networks respond in a gambling paradigm in which uncertainty was manipulated to increase demands for cognitive control. In one experiment, pupil diameter covaried with uncertainty during decision making and with the degree to which subsequent outcomes violated reward expectations. In a second experiment, fMRI showed that both uncertainty and unexpected outcomes modulated activation in a network of frontal regions. Thus, the frontal network supports multiple phases of the decision-making process including information regarding reward uncertainty and reward outcome. In contrast, striatal activation only tracked reward delivery, suggesting a distinct reward pathway that might, under certain circumstances, oppose the frontal network. These results are consistent with the interpretation that reward signals may bias recruitment of frontal networks that are linked to allocation of cognitive resources.

YNIMG Journal 2007 Journal Article

Unrest at rest: Default activity and spontaneous network correlations

• Randy L. Buckner
• Justin L. Vincent

A series of recent empirical observations demonstrate structured activity patterns that exist during passive task states. One observation is that a network of regions, referred to as the default network, shows preferentially greater activity during passive task states as compared to a wide range of active tasks. The second observation is that distributed regions spontaneously increase and decrease their activity together within functional–anatomic networks, even under anesthesia. We believe these rest activity patterns may reflect neural functions that consolidate the past, stabilize brain ensembles, and prepare us for the future. Accumulating data further suggest that differences in rest activity may be relevant to understanding clinical conditions such as Alzheimer’s disease and autism. Maps of spontaneous network correlations also provide tools for functional localization and study of comparative anatomy between primate species. For all of these reasons, we advocate the systematic exploration of rest activity.

YNIMG Journal 2006 Journal Article

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest

• Rahul S. Desikan
• Florent Ségonne
• Bruce Fischl
• Brian T. Quinn
• Bradford C. Dickerson
• Deborah Blacker
• Randy L. Buckner
• Anders M. Dale

In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0. 835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.

YNIMG Journal 2004 Journal Article

A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume

• Randy L. Buckner
• Denise Head
• Jamie Parker
• Anthony F. Fotenos
• Daniel Marcus
• John C. Morris
• Abraham Z. Snyder

Atlas normalization, as commonly used by functional data analysis, provides an automated solution to the widely encountered problem of correcting for head size variation in regional and whole-brain morphometric analyses, so long as an age- and population-appropriate target atlas is used. In the present article, we develop and validate an atlas normalization procedure for head size correction using manual total intracranial volume (TIV) measurement as a reference. The target image used for atlas transformation consisted of a merged young and old-adult template specifically created for cross age-span normalization. Automated atlas transformation generated the Atlas Scaling Factor (ASF) defined as the volume-scaling factor required to match each individual to the atlas target. Because atlas normalization equates head size, the ASF should be proportional to TIV. A validation analysis was performed on 147 subjects to evaluate ASF as a proxy for manual TIV measurement. In addition, 19 subjects were imaged on multiple days to assess test–retest reliability. Results indicated that the ASF was (1) equivalent to manual TIV normalization (r = 0. 93), (2) reliable across multiple imaging sessions (r = 1. 00; mean absolute percentage of difference = 0. 51%), (3) able to connect between-gender head size differences, and (4) minimally biased in demented older adults with marked atrophy. Hippocampal volume differences between nondemented (n = 49) and demented (n = 50) older adults (measured manually) were equivalent whether corrected using manual TIV or automated ASF (effect sizes of 1. 29 and 1. 46, respectively). To provide normative values, ASF was used to automatically derive estimated TIV (eTIV) in 335 subjects aged 15–96 including both clinically characterized nondemented (n = 77) and demented (n = 90) older adults. Differences in eTIV between nondemented and demented groups were negligible, thus failing to support the hypothesis that large premorbid brain size moderates Alzheimer's disease. Gender was the only robust factor that influenced eTIV. Men showed an approximately ∼12% larger eTIV than women. These results demonstrate that atlas normalization using appropriate template images provides a robust, automated method for head size correction that is equivalent to manual TIV correction in studies of aging and dementia. Thus, atlas normalization provides a common framework for both morphometric and functional data analysis.

YNIMG Journal 2002 Journal Article

The Feasibility of a Common Stereotactic Space for Children and Adults in fMRI Studies of Development

• E.Darcy Burgund
• Hyunseon Christine Kang
• James E. Kelly
• Randy L. Buckner
• Abraham Z. Snyder
• Steven E. Petersen
• Bradley L. Schlaggar

Thequestion 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 observed 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.

YNIMG Journal 2001 Journal Article

An Event-Related fMRI Study of Overt and Covert Word Stem Completion

• Erica D. Palmer
• Howard J. Rosen
• Jeffrey G. Ojemann
• Randy L. Buckner
• William M. Kelley
• Steven E. Petersen

In fMRI studies of language processing, it would be extremely useful to obtain high-quality images during tasks requiring spoken output. Recent studies have suggested that this may be possible, particularly if event-related fMRI methods are used. This study assesses the feasibility of acquiring interpretable images during speech by applying event-related methods to visual word stem completion, a task that has been studied extensively. On each trial, a different three-letter word stem (e. g. , COU) was presented visually and subjects were required to generate a word beginning with that stem (e. g. , COUSIN). In covert runs, subjects were instructed to say the word once to themselves, without moving their lips. In overt runs, subjects were instructed to say the word once aloud. Ten subjects were scanned during six overt runs and six covert runs at three presentation rates. Data were analyzed using an implementation of the general linear model making no assumptions about response shape. Images were relatively free of artifacts, and regions demonstrating task-related activation were similar to those reported in previous imaging studies. Regions active during overt task performance were similar to those active during covert task performance, with the addition of several regions commonly associated with motor aspects of speech production. Consistent with other studies, magnitude of activation was greater in the overt condition than in the covert condition, and there was a modest decrease in magnitude at the fastest presentation rate. Together, these results help to validate the use of event-related fMRI during tasks that require spoken output.

YNIMG Journal 2001 Journal Article

Code-specific repetition priming in frontal and posterior cortex

• Randy L. Buckner
• Mark E. Wheeler
• Luigi Maccotta
• Deborah Kerr
• Neal J. Cohen

YNIMG Journal 2001 Journal Article

Direct Comparison of Prefrontal Cortex Regions Engaged by Working and Long-Term Memory Tasks

• Todd S. Braver
• Deanna M. Barch
• William M. Kelley
• Randy L. Buckner
• Neal J. Cohen
• Francis M. Miezin
• Abraham Z. Snyder
• John M. Ollinger

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes–no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e. g. , task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e. g. , FP-PFC in LTM retrieval).

YNIMG Journal 2001 Journal Article

Dissociating memory retrieval processes using fMRI: Evidence that priming does not support recognition memory

• David I. Donaldson
• Steven E. Petersen
• Randy L. Buckner

YNIMG Journal 2001 Journal Article

Rapid self-paced event-related functional MRI

• Luigi Maccotta
• Jeffrey M. Zacks
• Randy L. Buckner

YNIMG Journal 2001 Journal Article

Rapid Self-Paced Event-Related Functional MRI: Feasibility and Implications of Stimulus- versus Response-Locked Timing

• Luigi Maccotta
• Jeffrey M. Zacks
• Randy L. Buckner

Many cognitive paradigms require self-paced responses or examine events that occur at unpredictable times. To explore whether functional MRI (fMRI) can accommodate such paradigms, a method allowing rapid, unpredictable trial pacing was developed and tested on 17 subjects using activation of the motor network as a model. Trial onset was determined solely by the subjects' self-paced responses and trials occurred, on average, less than 2 s apart. The hemodynamic response was estimated both in relation to stimulus onset (stimulus-locked) and in relation to behavioral response time (response-locked). Results yielded robust activation maps and hemodynamic response estimates. Specifically, significant activation in motor cortex, supplementary motor area (SMA), and cerebellum was observed both at the group and at the individual-subject level, confirming predicted patterns of brain activity. Moreover, the self-paced design resulted in even temporal sampling of the hemodynamic response across the image acquisition, allowing estimation of response parameters. Stimulus-locked analysis demonstrated strong correlation between hemodynamic- and behavioral-response timing both within and across subjects. Conversely, response-locked analysis showed minimal correlation with behavioral timing, suggesting effective resynchronization of the timing parameters. These results demonstrate fMRI procedures that can accommodate rapid, arbitrarily timed events and, in doing so, provide precise temporal estimates of the hemodynamic response.

YNIMG Journal 2001 Journal Article

Regional cortical thinning of the aging brain

• David H. Salat
• Randy L. Buckner
• Abraham Z. Snyder
• Rahul Desikan
• John C. Morris
• Andres M. Dale
• Bruce Fischl

YNIMG Journal 2001 Journal Article

Transient Activation during Block Transition

• Seiki Konishi
• David I. Donaldson
• Randy L. Buckner

Functional MRI (fMRI) data analysis of blocked-task paradigms typically considers brain activity present across a temporally extended task block relative to a reference block. An open question remains as to whether processes evolving with distinct temporal profiles are also present and can inform us about further functional–anatomic processes underlying task performance. To explore this question, a meta-analysis of data from these separate studies was performed. The meta-analysis specifically focused on detecting transient activation occurring at the onset and offset of task blocks. The composite data set from 39 subjects included four distinct task conditions (from various intentional encoding paradigms) that had equivalent block timing. Task block activation included a network of regions consistent with prior analyses of intentional encoding. Activation related to the block transitions included a set of transiently activated regions, consistent across all four separate task conditions. The most prominent activation was found in right frontal cortex along the dorsal extent of inferior frontal gyrus (near BA 6/44). Importantly, in one condition, this transient activation was present in the absence of a response across the task block suggesting dissociation between processes in support of ongoing task demands and those associated with transitions between blocks. Other prominent transient activations included posterior superior temporal sulcus, medial occipitoparietal sulcus, anterior insula, and anterior cingulate sulcus in the right hemisphere. These findings are discussed in relation to models of set shifting and competitive interactions between brain regions.

YNIMG Journal 2000 Journal Article

Neural Correlates of Episodic Retrieval Success

• Seiki Konishi
• Mark E. Wheeler
• David I. Donaldson
• Randy L. Buckner

Episodic memory retrieval involves multiple component processes, including those that occur when information is correctly remembered (retrieval success). The present study employed rapid-presentation event-related functional MRI that allowed different trial types with short intertrial intervals to be sorted such that the hemodynamic response associated with retrieval success could be extracted. Specifically, in an old/new episodic recognition task, hit trials (correctly recognized old items) and correct rejection trials (correctly rejected new items) were directly compared. The comparison revealed a mostly left-lateralized set of brain regions. Differential activation was most robust in left lateral parietal cortex and medial parietal cortex. Additional regions of differential activation included left anterior prefrontal cortex at or near Brodmann area 10, anterior insula, thalamus, anterior cingulate cortex, frontal cortex along inferior frontal gyrus, premotor cortex, and presupplementary motor area. These results suggest that left frontal and parietal regions modulate activity based on the successful retrieval of information from episodic memory. We discuss these findings in the context of several recent investigations that provide converging results as well as prior studies that have failed to detect these changes.

YNIMG Journal 1998 Journal Article

Functional–Anatomic Study of Episodic Retrieval

• Randy L. Buckner
• Wilma Koutstaal
• Daniel L. Schacter
• Anders M. Dale
• Michael Rotte
• Bruce R. Rosen

In a companion paper (R. L. Buckneret al. ,1998, NeuroImage 7, 151–162) we used fMRI to identify brain areas activated by episodic memory retrieval. Prefrontal areas were shown to differentiate component processes related to retrieval success and retrieval effort in block-designed paradigms. Importantly, a right anterior prefrontal area was most active during task blocks involving greatest retrieval success, consistent with an earlier PET study by M. D. Rugget al. (1996, Brain 119, 2073–2083). However, manipulation of these variables within the context of blocked trials confounds differences related to varying levels of retrieval success with potential shifts in subjects' strategies due to changes in the probability of target events across blocks. To test more rigorously the hypothesis that certain areas are directly related to retrieval success, we adopted recently developed procedures for event-related fMRI. Fourteen subjects studied words under deep encoding and were then tested in a mixed trial paradigm where old and new words were randomly presented. This recognition testing procedure activated similar areas to the blocked trial paradigm, with all areas showing similar levels of activation across old and new items. Of critical importance, significant activation was detected in right anterior prefrontal cortex for new items when subjects correctly indicated they were new (correct rejections). These findings go against the retrieval success hypothesis as formally proposed and provide an important constraint for interpretation of this region's role in episodic retrieval. Furthermore, anterior prefrontal activation was found to occur late, relative to other brain areas, suggesting that it may be involved in retrieval verification or monitoring processes or perhaps even in anticipation of subsequent trial events (although an alternative possibility, that the late onset is mediated by a late vascular response, cannot be ruled out). These findings and their relation to the results obtained in the companion blocked-trial paradigm are discussed.

YNIMG Journal 1998 Journal Article

Functional–Anatomic Study of Episodic Retrieval Using fMRI

• Randy L. Buckner
• Wilma Koutstaal
• Daniel L. Schacter
• Anthony D. Wagner
• Bruce R. Rosen

A number of recent functional imaging studies have identified brain areas activated during tasks involving episodic memory retrieval. The identification of such areas provides a foundation for targeted hypotheses regarding the more specific contributions that these areas make to episodic retrieval. As a beginning effort toward such an endeavor, whole-brain functional magnetic resonance imaging (fMRI) was used to examine 14 subjects during episodic word recognition in a block-designed fMRI experiment. Study conditions were manipulated by presenting either shallow or deep encoding tasks. This manipulation yielded two recognition conditions that differed with regard to retrieval effort and retrieval success: shallow encoding yielded low levels of recognition success with high levels of retrieval effort, and deep encoding yielded high levels of recognition success with low levels of effort. Many brain areas were activated in common by these two recognition conditions compared to a low-level fixation condition, including left and right prefrontal regions often detected during PET episodic retrieval paradigms (e. g. , R. L. Buckneret al. ,1996, J. Neurosci. 16, 6219–6235) thereby generalizing these findings to fMRI. Characterization of the activated regions in relation to the separate recognition conditions showed (1) bilateral anterior insular regions and a left dorsal prefrontal region were more active after shallow encoding, when retrieval demanded greatest effort, and (2) right anterior prefrontal cortex, which has been implicated in episodic retrieval, was most active during successful retrieval after deep encoding. We discuss these findings in relation to component processes involved in episodic retrieval and in the context of a companion study using event-related fMRI.

YNIMG Journal 1997 Journal Article

Late Onset of Anterior Prefrontal Activity during True and False Recognition: An Event-Related fMRI Study

• Daniel L. Schacter
• Randy L. Buckner
• Wilma Koutstaal
• Anders M. Dale
• Bruce R. Rosen

Previous studies using PET and fMRI to examine memory retrieval have been limited by the requirement to test different types of items in separate blocks and to average data across items and response types within blocks. We used recently developed procedures for analyzing event-related mixed trial data from fMRI experiments to compare brain activity during true recognition of previously studied words and false recognition of semantic associates. A previous PET study using blocked testing procedures reported similarities and differences in rCBF patterns associated with true and false recognition (Schacteret al. ,1996a). We examined brain activity during blocked testing of studied words and nonstudied semantic associates (similar to PET), and also during event-related mixed trials, where studied words and nonstudied semantic associates are intermixed. Six subjects initially heard lists of semantically related words and were later tested for old/new recognition with studied words and nonstudied semantic associates, either in separate blocks or intermixed randomly for the event-related analysis. Compared to a fixation control condition, a variety of regions previously reported in the PET study showed significant activation for both true and false recognition, including anterior prefrontal, frontal opercular, medial parietal, and visual cortex extending into hippocampal/parahippocampal regions. Differences across trial types were not clearly present. Event-related analyses of time course data show a relatively late onset and sustained duration for anterior prefrontal signal changes compared to signal changes in other activated regions. Further study is needed to resolve whether this late onset originates from variance in hemodynamic response properties or is attributable to delayed neural activity. The delayed onset is consistent with the idea that anterior prefrontal regions participate in postretrieval monitoring processes.