Abraham Z Snyder

Publications of Abraham Z Snyder

• Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities.

  Authors: Joseph M Mettenburg, Tammie L Benzinger, Joshua S Shimony, Abraham Z Snyder, Yvette I Sheline

  NeuroImage. 05/2012; 60(4):2182-90.

  Traditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging providesTraditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. 51 depressed and 16 non-depressed, age- and cerebrovascular risk factor-matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. Widespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. White matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible mechanism for underlying myelin injury is chronic white matter ischemia related to intrinsic cerebrovascular disease. In some regions such as the cingulate bundle, the white matter injury related to late life depression appears to be independent of and compounded by age-related changes. The correlations with neuropsychological testing indicate the essential effects of white matter injury on functional status. Lastly, response to treatment may depend on the extent of white matter injury, suggesting a need for intact functional networks.

• Steps toward optimizing motion artifact removal in functional connectivity MRI; a reply to Carp.

  Authors: Jonathan D Power, Kelly Anne Barnes, Abraham Z Snyder, Bradley L Schlaggar, Steven E Petersen

  NeuroImage. 03/2012;

• Individual variability in functional connectivity predicts performance of a perceptual task.

  Authors: Antonello Baldassarre, Christopher M Lewis, Giorgia Committeri, Abraham Z Snyder, Gian Luca Romani, Maurizio Corbetta

  Proceedings of the National Academy of Sciences of the United States of America. 02/2012; 109(9):3516-21.

  People differ in their ability to perform novel perceptual tasks, both during initial exposure and in the rate of improvement with practice. It is also known that regions of the brain recruited byPeople differ in their ability to perform novel perceptual tasks, both during initial exposure and in the rate of improvement with practice. It is also known that regions of the brain recruited by particular tasks change their activity during learning. Here we investigate neural signals predictive of individual variability in performance. We used resting-state functional MRI to assess functional connectivity before training on a novel visual discrimination task. Subsequent task performance was related to functional connectivity measures within portions of visual cortex and between visual cortex and prefrontal association areas. Our results indicate that individual differences in performing novel perceptual tasks can be related to individual differences in spontaneous cortical activity.

• A quantitative spatial comparison of high-density diffuse optical tomography and fMRI cortical mapping.

  Authors: Adam T Eggebrecht, Brian R White, Silvina L Ferradal, Chunxiao Chen, Yuxuan Zhan, Abraham Z Snyder, Hamid Dehghani, Joseph P Culver

  NeuroImage. 02/2012;

  Functional neuroimaging commands a dominant role in current neuroscience research. However its use in bedside clinical and certain neuro-scientific studies has been limited because the current toolsFunctional neuroimaging commands a dominant role in current neuroscience research. However its use in bedside clinical and certain neuro-scientific studies has been limited because the current tools lack the combination of being non-invasive, non-ionizing and portable while maintaining moderate resolution and localization accuracy. Optical neuroimaging satisfies many of these requirements, but, until recent advances in high-density diffuse optical tomography (HD-DOT), has been hampered by limited resolution. While early results of HD-DOT have been promising, a quantitative voxel-wise comparison and validation of HD-DOT against the gold standard of functional magnetic resonance imaging (fMRI) has been lacking. Herein, we provide such an analysis within the visual cortex using matched visual stimulation protocols in a single group of subjects (n=5) during separate HD-DOT and fMRI scanning sessions. To attain the needed voxel-to-voxel co-registration between HD-DOT and fMRI image spaces, we implemented subject-specific head modeling that incorporated MRI anatomy, detailed segmentation, and alignment of source and detector positions. Comparisons of the visual responses found an average localization error between HD-DOT and fMRI of 4.4+/-1mm, significantly less than the average distance between cortical gyri. This specificity demonstrates that HD-DOT has sufficient image quality to be useful as a surrogate for fMRI.

• Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion.

  Authors: Jonathan D Power, Kelly A Barnes, Abraham Z Snyder, Bradley L Schlaggar, Steven E Petersen

  NeuroImage. 02/2012; 59(3):2142-54.

  Here, we demonstrate that subject motion produces substantial changes in the timecourses of resting state functional connectivity MRI (rs-fcMRI) data despite compensatory spatial registration andHere, we demonstrate that subject motion produces substantial changes in the timecourses of resting state functional connectivity MRI (rs-fcMRI) data despite compensatory spatial registration and regression of motion estimates from the data. These changes cause systematic but spurious correlation structures throughout the brain. Specifically, many long-distance correlations are decreased by subject motion, whereas many short-distance correlations are increased. These changes in rs-fcMRI correlations do not arise from, nor are they adequately countered by, some common functional connectivity processing steps. Two indices of data quality are proposed, and a simple method to reduce motion-related effects in rs-fcMRI analyses is demonstrated that should be flexibly implementable across a variety of software platforms. We demonstrate how application of this technique impacts our own data, modifying previous conclusions about brain development. These results suggest the need for greater care in dealing with subject motion, and the need to critically revisit previous rs-fcMRI work that may not have adequately controlled for effects of transient subject movements.

• A brief history of the resting state: The Washington University perspective.

  Authors: Abraham Z Snyder, Marcus E Raichle

  NeuroImage. 01/2012;

  We present a history of the concepts and developments that have led us to focus on the resting state as an object of study. We then discuss resting state research performed in our laboratory sinceWe present a history of the concepts and developments that have led us to focus on the resting state as an object of study. We then discuss resting state research performed in our laboratory since 2005 with an emphasis on papers of particular interest.

• Role of family history for Alzheimer biomarker abnormalities in the adult children study.

  Authors: Chengjie Xiong, Catherine M Roe, Virginia Buckles, Anne Fagan, David Holtzman, David Balota, Janet Duchek, Martha Storandt, Mark Mintun, Elizabeth Grant, Abraham Z Snyder, Denise Head, Tammie L S Benzinger, Joseph Mettenburg, John Csernansky, John C Morris

  Archives of neurology. 10/2011; 68(10):1313-9.

  To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities. Adult Children Study. Washington University's Charles F. and Joanne Knight Alzheimer'sTo assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities. Adult Children Study. Washington University's Charles F. and Joanne Knight Alzheimer's Disease Research Center. A total of 269 cognitively normal middle- to older-aged individuals with and without an FH for AD. Clinical and cognitive measures, magnetic resonance imaging-based brain volumes, diffusion tensor imaging-based white matter microstructure, cerebrospinal fluid biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography using the [(11)C] benzothiazole tracer, Pittsburgh compound B. A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid Aβ42; the ε4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid Aβ42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive FH compared with the decrease for those without. The variation of cerebrospinal fluid tau and Pittsburgh compound B mean cortical binding potential increased by age. For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential. A positive FH was associated with decreased fractional anisotropy from diffusion tensor imaging in the genu and splenium of the corpus callosum. Independent of APOE4, FH is associated with age-related change of several cerebrospinal fluid, Pittsburgh compound B, and diffusion tensor imaging biomarkers in cognitively normal middle- to older-aged individuals, suggesting that non- APOE susceptibility genes for AD influence AD biomarkers.

• Upstream dysfunction of somatomotor functional connectivity after corticospinal damage in stroke.

  Authors: Alex R Carter, Kevin R Patel, Serguei V Astafiev, Abraham Z Snyder, Jennifer Rengachary, Michael J Strube, Anna Pope, Joshua S Shimony, Catherine E Lang, Gordon L Shulman, Maurizio Corbetta

  Neurorehabilitation and neural repair. 07/2011; 26(1):7-19.

  Recent studies have shown that focal injuries can have remote effects on network function that affect behavior, but these network-wide repercussions are poorly understood. This study tested theRecent studies have shown that focal injuries can have remote effects on network function that affect behavior, but these network-wide repercussions are poorly understood. This study tested the hypothesis that lesions specifically to the outflow tract of a distributed network can result in upstream dysfunction in structurally intact portions of the network. In the somatomotor system, this upstream dysfunction hypothesis predicted that lesions of the corticospinal tract might be associated with functional disruption within the system. Motor impairment might then reflect the dual contribution of corticospinal damage and altered network functional connectivity. A total of 23 subacute stroke patients and 13 healthy controls participated in the study. Corticospinal tract damage was quantified using a template of the tract generated from diffusion tensor imaging in healthy controls. Somatomotor network functional integrity was determined by resting state functional connectivity magnetic resonance imaging. The extent of corticospinal damage was negatively correlated with interhemispheric resting functional connectivity, in particular with connectivity between the left and right central sulcus. Although corticospinal damage accounted for much of the variance in motor performance, the behavioral impact of resting connectivity was greater in subjects with mild or moderate corticospinal damage and less in those with severe corticospinal damage. Our results demonstrated that dysfunction of cortical functional connectivity can occur after interruption of corticospinal outflow tracts and can contribute to impaired motor performance. Recognition of these secondary effects from a focal lesion is essential for understanding brain-behavior relationships after injury, and they may have important implications for neurorehabilitation.

• Resting-state activity in development and maintenance of normal brain function.

  Authors: Carolyn E Pizoli, Manish N Shah, Abraham Z Snyder, Joshua S Shimony, David D Limbrick, Marcus E Raichle, Bradley L Schlaggar, Matthew D Smyth

  Proceedings of the National Academy of Sciences of the United States of America. 06/2011; 108(28):11638-43.

  One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functionalOne of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

• Premotor functional connectivity predicts impulsivity in juvenile offenders.

  Authors: Benjamin J Shannon, Marcus E Raichle, Abraham Z Snyder, Damien A Fair, Kathryn L Mills, Dongyang Zhang, Kevin Bache, Vince D Calhoun, Joel T Nigg, Bonnie J Nagel, Alexander A Stevens, Kent A Kiehl

  Proceedings of the National Academy of Sciences of the United States of America. 06/2011; 108(27):11241-5.

  Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, weTeenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain-behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.

• Detection of blast-related traumatic brain injury in U.S. military personnel.

  Authors: Christine L Mac Donald, Ann M Johnson, Dana Cooper, Elliot C Nelson, Nicole J Werner, Joshua S Shimony, Abraham Z Snyder, Marcus E Raichle, John R Witherow, Raymond Fang, Stephen F Flaherty, David L Brody

  The New England journal of medicine. 06/2011; 364(22):2091-100.

  Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. We tested the hypothesis thatBlast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectable intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P=0.002), and in the right orbitofrontal white matter (P=0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.).

• Functional connectivity MRI in infants: exploration of the functional organization of the developing brain.

  Authors: Christopher D Smyser, Abraham Z Snyder, Jeffrey J Neil

  NeuroImage. 03/2011; 56(3):1437-52.

  Advanced neuroimaging techniques have been increasingly applied to the study of preterm and term infants in an effort to further define the functional cerebral architecture of the developing brain.Advanced neuroimaging techniques have been increasingly applied to the study of preterm and term infants in an effort to further define the functional cerebral architecture of the developing brain. Despite improved understanding of the complex relationship between structure and function obtained through these investigations, significant questions remain regarding the nature, location, and timing of the maturational changes which occur during early development. Functional connectivity magnetic resonance imaging (fcMRI) utilizes spontaneous, low frequency (< 0.1 Hz), coherent fluctuations in blood oxygen level dependent (BOLD) signal to identify networks of functional cerebral connections. Due to the intrinsic characteristics of its image acquisition and analysis, fcMRI offers a novel neuroimaging approach well suited to investigation of infants. Recently, this methodology has been successfully applied to examine neonatal populations, defining normative patterns of large-scale neural network development in the maturing brain. The resting-state networks (RSNs) identified in these studies reflect the evolving cerebral structural architecture, presumably driven by varied genetic and environmental influences. Principal features of these investigations and their role in characterization of the tenets of neural network development during this critical developmental period are highlighted in this review. Despite these successes, optimal methods for fcMRI data acquisition and analysis for this population have not yet been defined. Further, appropriate schemes for interpretation and translation of fcMRI results remain unknown, a matter of increasing importance as functional neuroimaging findings are progressively applied in the clinical arena. Notwithstanding these concerns, fcMRI provides insight into the earliest forms of cerebral connectivity and therefore holds great promise for future neurodevelopmental investigations.

• Imaging of functional connectivity in the mouse brain.

  Authors: Brian R White, Adam Q Bauer, Abraham Z Snyder, Bradley L Schlaggar, Jin-Moo Lee, Joseph P Culver

  PloS one. 01/2011; 6(1):e16322.

  Functional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easilyFunctional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easily perform large-scale functional neuroimaging in mice would enable the discovery of functional correlates of genetic manipulations and bridge with mouse models of disease. To satisfy this need, we combined resting-state functional connectivity mapping with optical intrinsic signal imaging (fcOIS). We demonstrate functional connectivity in mice through highly detailed fcOIS mapping of resting-state networks across most of the cerebral cortex. Synthesis of multiple network connectivity patterns through iterative parcellation and clustering provides a comprehensive map of the functional neuroarchitecture and demonstrates identification of the major functional regions of the mouse cerebral cortex. The method relies on simple and relatively inexpensive camera-based equipment, does not require exogenous contrast agents and involves only reflection of the scalp (the skull remains intact) making it minimally invasive. In principle, fcOIS allows new paradigms linking human neuroscience with the power of molecular/genetic manipulations in mouse models.

• Modulation of the brain's functional network architecture in the transition from wake to sleep.

  Authors: Linda J Larson-Prior, Jonathan D Power, Justin L Vincent, Tracy S Nolan, Rebecca S Coalson, John Zempel, Abraham Z Snyder, Bradley L Schlaggar, Marcus E Raichle, Steven E Petersen

  Progress in brain research. 01/2011; 193:277-94.

  The transition from quiet wakeful rest to sleep represents a period over which attention to the external environment fades. Neuroimaging methodologies have provided much information on the shift inThe transition from quiet wakeful rest to sleep represents a period over which attention to the external environment fades. Neuroimaging methodologies have provided much information on the shift in neural activity patterns in sleep, but the dynamic restructuring of human brain networks in the transitional period from wake to sleep remains poorly understood. Analysis of electrophysiological measures and functional network connectivity of these early transitional states shows subtle shifts in network architecture that are consistent with reduced external attentiveness and increased internal and self-referential processing. Further, descent to sleep is accompanied by the loss of connectivity in anterior and posterior portions of the default-mode network and more locally organized global network architecture. These data clarify the complex and dynamic nature of the transitional period between wake and sleep and suggest the need for more studies investigating the dynamics of these processes.

• APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42.

  Authors: Yvette I Sheline, John C Morris, Abraham Z Snyder, Joseph L Price, Zhizi Yan, Gina D'Angelo, Collin Liu, Sachin Dixit, Tammie Benzinger, Anne Fagan, Alison Goate, Mark A Mintun

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 12/2010; 30(50):17035-40.

  Identifying high-risk populations is an important component of disease prevention strategies. One approach for identifying at-risk populations for Alzheimer's disease (AD) is examining neuroimagingIdentifying high-risk populations is an important component of disease prevention strategies. One approach for identifying at-risk populations for Alzheimer's disease (AD) is examining neuroimaging parameters that differ between patients, including functional connections known to be disrupted within the default-mode network. We have previously shown these same disruptions in cognitively normal elderly who have amyloid-β (Aβ) plaques [detected using Pittsburgh Compound B (PIB) PET imaging], suggesting neuronal toxicity of plaques. Here we sought to determine if pathological effects of apolipoprotein E ε4 (APOE4) genotype could be seen independent of Aβ plaque toxicity by examining resting state fMRI functional connectivity (fcMRI) in participants without preclinical fibrillar amyloid deposition (PIB-). Cognitively normal participants enrolled in longitudinal studies (n = 100, mean age = 62) who were PIB- were categorized into those with and without an APOE4 allele and studied using fcMRI. APOE4 allele carriers (E4+) differed significantly from E4- in functional connectivity of the precuneus to several regions previously defined as having abnormal connectivity in a group of AD participants. These effects were observed before any manifestations of cognitive changes and in the absence of brain fibrillar Aβ plaque deposition, suggesting that early manifestations of a genetic effect can be detected using fcMRI and that these changes may antedate the pathological effects of fibrillar amyloid plaque toxicity.

• Regional aerobic glycolysis in the human brain.

  Authors: S Neil Vaishnavi, Andrei G Vlassenko, Melissa M Rundle, Abraham Z Snyder, Mark A Mintun, Marcus E Raichle

  Proceedings of the National Academy of Sciences of the United States of America. 10/2010; 107(41):17757-62.

  Aerobic glycolysis is defined as glucose utilization in excess of that used for oxidative phosphorylation despite sufficient oxygen to completely metabolize glucose to carbon dioxide and water.Aerobic glycolysis is defined as glucose utilization in excess of that used for oxidative phosphorylation despite sufficient oxygen to completely metabolize glucose to carbon dioxide and water. Aerobic glycolysis is present in the normal human brain at rest and increases locally during increased neuronal activity; yet its many biological functions have received scant attention because of a prevailing energy-centric focus on the role of glucose as substrate for oxidative phosphorylation. As an initial step in redressing this neglect, we measured the regional distribution of aerobic glycolysis with positron emission tomography in 33 neurologically normal young adults at rest. We show that the distribution of aerobic glycolysis in the brain is differentially present in previously well-described functional areas. In particular, aerobic glycolysis is significantly elevated in medial and lateral parietal and prefrontal cortices. In contrast, the cerebellum and medial temporal lobes have levels of aerobic glycolysis significantly below the brain mean. The levels of aerobic glycolysis are not strictly related to the levels of brain energy metabolism. For example, sensory cortices exhibit high metabolic rates for glucose and oxygen consumption but low rates of aerobic glycolysis. These striking regional variations in aerobic glycolysis in the normal human brain provide an opportunity to explore how brain systems differentially use the diverse cell biology of glucose in support of their functional specializations in health and disease.

• The temporal structures and functional significance of scale-free brain activity.

  Authors: Biyu J He, John M Zempel, Abraham Z Snyder, Marcus E Raichle

  Neuron. 05/2010; 66(3):353-69.

  Scale-free dynamics, with a power spectrum following P proportional to f(-beta), are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is oftenScale-free dynamics, with a power spectrum following P proportional to f(-beta), are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with beta being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications.

• Dynamic susceptibility contrast MRI with localized arterial input functions.

  Authors: John J Lee, G Larry Bretthorst, Colin P Derdeyn, William J Powers, Tom O Videen, Abraham Z Snyder, Joanne Markham, Joshua S Shimony

  Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 05/2010; 63(5):1305-14.

  Compared to gold-standard measurements of cerebral perfusion with positron emission tomography using H(2)[(15)O] tracers, measurements with dynamic susceptibility contrast MR are more accessible,Compared to gold-standard measurements of cerebral perfusion with positron emission tomography using H(2)[(15)O] tracers, measurements with dynamic susceptibility contrast MR are more accessible, less expensive, and less invasive. However, existing methods for analyzing and interpreting data from dynamic susceptibility contrast MR have characteristic disadvantages that include sensitivity to incorrectly modeled delay and dispersion in a single, global arterial input function. We describe a model of tissue microcirculation derived from tracer kinetics that estimates for each voxel a unique, localized arterial input function. Parameters of the model were estimated using Bayesian probability theory and Markov-chain Monte Carlo, circumventing difficulties arising from numerical deconvolution. Applying the new method to imaging studies from a cohort of 14 patients with chronic, atherosclerotic, occlusive disease showed strong correlations between perfusion measured by dynamic susceptibility contrast MR with localized arterial input function and perfusion measured by quantitative positron emission tomography with H(2)[(15)O]. Regression to positron emission tomography measurements enabled conversion of dynamic susceptibility contrast MR to a physiologic scale. Regression analysis for localized arterial input function gave estimates of a scaling factor for quantitation that described perfusion accurately in patients with substantial variability in hemodynamic impairment.

• Comment on "Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI" and "Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area".

  Authors: Serguei V Astafiev, Abraham Z Snyder, Gordon L Shulman, Maurizio Corbetta

  Science (New York, N.Y.). 04/2010; 328(5976):309; author reply 309.

  Minzenberg et al. (Reports, 12 December 2008, p. 1700) and Schmidt et al. (Reports, 24 April 2009, p. 516) reported blood oxygen level-dependent (BOLD) responses in the human locus coeruleus (LC).Minzenberg et al. (Reports, 12 December 2008, p. 1700) and Schmidt et al. (Reports, 24 April 2009, p. 516) reported blood oxygen level-dependent (BOLD) responses in the human locus coeruleus (LC). Here, we show that these LC responses do not correspond to the anatomical location of the LC and present cautionary data concerning the quality of BOLD signals measured from the LC using standard functional magnetic resonance imaging acquisition parameters.

• Right hemisphere dominance during spatial selective attention and target detection occurs outside the dorsal frontoparietal network.

  Authors: Gordon L Shulman, Daniel L W Pope, Serguei V Astafiev, Mark P McAvoy, Abraham Z Snyder, Maurizio Corbetta

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 03/2010; 30(10):3640-51.

  Spatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging studies, however, have reported bilateralSpatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging studies, however, have reported bilateral blood-oxygenation-level-dependent responses in dorsal frontoparietal regions during anticipatory shifts of attention to a location (Kastner et al., 1999; Corbetta et al., 2000; Hopfinger et al., 2000). Right-lateralized activity has mainly been reported in ventral frontoparietal regions for shifts of attention to an unattended target stimulus (Arrington et al., 2000; Corbetta et al., 2000). However, clear conclusions cannot be drawn from these studies because hemispheric asymmetries were not assessed using direct voxelwise comparisons of activity in left and right hemispheres. Here, we used this technique to measure hemispheric asymmetries during shifts of spatial attention evoked by a peripheral cue stimulus and during target detection at the cued location. Stimulus-driven shifts of spatial attention in both visual fields evoked right-hemisphere dominant activity in temporoparietal junction (TPJ). Target detection at the attended location produced a more widespread right hemisphere dominance in frontal, parietal, and temporal cortex, including the TPJ region asymmetrically activated during shifts of spatial attention. However, hemispheric asymmetries were not observed during either shifts of attention or target detection in the dorsal frontoparietal regions (anterior precuneus, medial intraparietal sulcus, frontal eye fields) that showed the most robust activations for shifts of attention. Therefore, right hemisphere dominance during stimulus-driven shifts of spatial attention and target detection reflects asymmetries in cortical regions that are largely distinct from the dorsal frontoparietal network involved in the control of selective attention.