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Propofol total intravenous anesthesia is a common choice to anesthetize patients with increased intracranial pressure, reducing cerebral blood flow while maintaining cerebrovascular reactivity to CO 2 . Propofol and alfaxalone are commonly used for total intravenous anesthesia in dogs, but the effects of alfaxalone on cerebral blood flow and cerebrovascular reactivity to CO 2 are unknown. Our hypothesis was that alfaxalone would not be significantly different to propofol, while isoflurane would increase cerebral blood flow and decrease cerebrovascular reactivity to CO 2 . Six healthy hound dogs were evaluated in this randomized crossover trial. Dogs were anesthetized with 7.5 mg/kg propofol, 3 mg/kg alfaxalone or 8 % sevoflurane, mechanically ventilated and maintained with propofol (400 µg/kg/min), alfaxalone (150 µg/kg/min) or 1.7 % end-tidal isoflurane, respectively, with one week washout between treatments. Cerebral blood flow and cerebrovascular reactivity to CO 2 during hypercapnic and hypocapnic challenges were measured using arterial spin labelling and blood oxygen level-dependent magnetic resonance imaging sequences, respectively. Median (interquartile range, IQR) normocapnic cerebral blood flow was significantly lower (P = 0.016) with alfaxalone compared to isoflurane, in the whole brain 15.39 mL/min/100 g (14.90-19.90 mL/min/100 g) vs. 34.10 mL/min/100 g (33.35-43.17 mL/min/100 g), the grey matter 14.57 mL/min/100 g (13.66-18.72 mL/min/100 g) vs. 32.37 mL/min/100 g (31.03-42.99 mL/min/100 g), the caudal brain 15.47 mL/min/100 g (13.37-21.45 mL/min/100 g) vs. 36.85 mL/min/100 g (32.50-47.18 mL/min/100 g) and the temporal lobe grey matter 18.80 mL/min/100 g (15.89-20.84 mL/min/100 g) vs. 43.32 (36.07-43.58 mL/min/100 g). Median (IQR) hypocapnic cerebrovascular reactivity to CO 2 was significantly higher (P = 0.016) for alfaxalone compared to isoflurane 8.85 %S/mm Hg (6.92-10.44 %S/mm Hg) vs. 3.90 %S/mm Hg (3.80-4.33 %S/mm Hg). Alfaxalone maintained lower cerebral blood flow and higher hypocapnic cerebrovascular reactivity to CO 2 than isoflurane., Competing Interests: Conflict of interest statement Ludovica Chiavaccini is currently an associate editor for Veterinary Anesthesia and Analgesia. None of the authors have any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men., (© 2020 Society for the Study of Addiction.)

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers to measure changes in these features. Critical to the performance of a quantitative imaging biomarker in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method, and metrics used to assess a quantitative imaging biomarker for clinical use. It is therefore difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America and the Quantitative Imaging Biomarker Alliance with technical, radiological, and statistical experts developed a set of technical performance analysis methods, metrics, and study designs that provide terminology, metrics, and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of quantitative imaging biomarker performance studies so that results from multiple studies can be compared, contrasted, or combined., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Purpose: (i) to validate blood oxygenation level dependent (BOLD) breathhold cerebrovascular reactivity (BH CVR) mapping as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional MRI (fMRI) for sensorimotor mapping, and (ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group., Materials and Methods: We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional)., Results: Motor task mean T-value was significantly higher in the contralesional ROIs (6.00 ± 1.74 versus 4.34 ± 1.68; P = 0.00004) as well as the BH mean T-value (4.74 ± 2.30 versus 4.09 ± 2.50; P = 0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z = 2.99; P = 0.03). Actual NVU prevalence was 75%., Conclusion: Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks)., (© 2013 Wiley Periodicals, Inc.)

Language production requires multiple stages of processing (e.g., semantic retrieval, lexical selection), each of which may involve distinct brain regions. Distractor words can be combined with picture naming to examine factors that influence language production. Phonologically-related distractors have been found to speed picture naming (facilitation), while slower response times and decreased accuracy (interference) generally occur when a distractor is categorically related to the target image. However, other types of semantically-related distractors have been reported to produce a facilitative effect (e.g., associative, part-whole). The different pattern of results for different types of semantically-related distractors raises the question about how the nature of the semantic relation influences the effect of the distractor. To explore the nature of these semantic effects further, we used functional MRI to examine the influence of four types of written distractors on brain activation during overt picture naming. Distractors began with the same sound, were categorically-related, part of the object to be named, or were unrelated to the picture. Phonologically-related trials elicited greater activation than both semantic conditions (categorically-related and part-whole) in left insula and bilateral parietal cortex, regions that have been attributed to phonological aspects of production and encoding, respectively. Semantic conditions elicited greater activation than phonological trials in left posterior MTG, a region that has been linked to concept retrieval and semantic integration. Overall, the two semantic conditions did not differ substantially in their functional activation which suggests a similarity in the semantic demands and lexical competition across these two conditions.

Purpose: To evaluate the reproducibility of presurgical functional MRI (fMRI) language mapping based on test-retest scans, comparing traditional activation t-maps to relative activation maps normalized by activation mapping as percentage of local excitation (AMPLE)., Materials and Methods: Language fMRI scans were performed by 12 healthy volunteer subjects undergoing a standard clinical presurgical mapping protocol in multiple independent scan sessions. Objective relative AMPLE activation maps were generated automatically by normalizing statistical t-value maps to the local peak activation amplitude within each functional brain region. The spatial distribution of activation was quantified and compared across mapping algorithms, subjects, scanners, and pulse sequences., Results: The spatial distribution of traditional blood oxygen level-dependent (BOLD) t-value statistical activation maps was highly variable in test-retest scans of single subjects, whereas AMPLE normalized maps were highly reproducible in terms of the location, hemispheric laterality, and spatial extent of relative activation. AMPLE map reproducibility was good regardless of scanner, field strength, or pulse sequence used, but reproducibility was best for scans acquired on the same scanner using the same pulse sequence., Conclusion: Reproducibility of the spatial pattern of BOLD activation makes relative amplitude fMRI mapping a useful normalization tool for clinical imaging of language function, where reproducibility and quantitative measurements are critical concerns., (Copyright © 2012 Wiley Periodicals, Inc.)

This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery., (Copyright © 2012 Wiley Periodicals, Inc.)

Functional magnetic resonance imaging (fMRI) is based on correlating blood oxygen-level dependent (BOLD) signal fluctuations in the brain with other time-varying signals. Although the most common reference for correlation is the timing of a behavioral task performed during the scan, many other behavioral and physiological variables can also influence fMRI signals. Variations in cardiac and respiratory functions in particular are known to contribute significant BOLD signal fluctuations. Variables such as skin conduction, eye movements, and other measures that may be relevant to task performance can also be correlated with BOLD signals and can therefore be used in image analysis to differentiate multiple components in complex brain activity signals. Combining real-time recording and data management of multiple behavioral and physiological signals in a way that can be routinely used with any task stimulus paradigm is a non-trivial software design problem. Here we discuss software methods that allow users control of paradigm-specific audio-visual or other task stimuli combined with automated simultaneous recording of multi-channel behavioral and physiological response variables, all synchronized with sub-millisecond temporal accuracy. We also discuss the implementation and importance of real-time display feedback to ensure data quality of all recorded variables. Finally, we discuss standards and formats for storage of temporal covariate data and its integration into fMRI image analysis. These neuroinformatics methods have been adopted for behavioral task control at all sites in the Functional Biomedical Informatics Research Network (FBIRN) multi-center fMRI study.

The ability to maintain information over short periods of time (i.e., working memory) is critically important in a variety of cognitive functions including language, planning, and decision-making. Recent functional Magnetic Resonance Imaging (fMRI) research with healthy adults has shown that brain activations evoked during the delay interval of working memory tasks can be reduced by the presentation of distracting emotional events, suggesting that emotional events may take working-memory processes momentarily offline. Both executive function and emotional processing are disrupted in schizophrenia, and here we sought to elucidate the effect of emotional distraction upon brain activity in schizophrenic and healthy adults performing a verbal working memory task. During the delay period between the memoranda and memory probe items, emotional and neutral distractors differentially influenced brain activity in these groups. In healthy adults, the hemodynamic response from posterior cingulate, orbital frontal cortex, and the parietal lobe strongly differentiated emotional from neutral distractors. In striking contrast, schizophrenic adults showed no significant differences in brain activation when processing emotional and neutral distractors. Moreover, the influence of emotional distractors extended into the memory probe period in healthy, but not schizophrenic, adults. The results suggest that although emotional items are highly salient for healthy adults, emotional items are no more distracting than neutral ones to individuals with schizophrenia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the performance of a relative activation amplitude algorithm, versus standard t-value thresholding, for reliably establishing the location, amplitude, and spatial extent of functional magnetic resonance imaging (fMRI) brain activation for presurgical planning., Materials and Methods: Diagnostic fMRI maps from 42 neurosurgical patients performing a simple hand movement task were analyzed. Relative activation maps were made by normalizing statistical t-value maps to the local peak activation amplitude within each functional brain region. The spatial distribution of activation was quantified and compared across mapping algorithms, subjects, and scan duration., Results: Whereas the spatial distribution of blood oxygenation level-dependent (BOLD) t-value statistical activation maps was highly variable across subjects and scan duration, the spatial distribution of relative activation maps was highly reproducible both within individual subjects and across different subjects. In every case the 40% most active voxels in the cortical hand region were consistently localized to the pre- and postcentral gyri of the sensorimotor cortex., Conclusion: The reproducibility and anatomical specificity of the spatiotemporal pattern of BOLD activation makes relative amplitude fMRI mapping a useful tool for clinical imaging, where accuracy, reproducibility, and quality control are critical concerns.

Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders.

Functional magnetic resonance imaging (fMRI) does not typically yield highly reproducible maps of brain activation. Maps can vary significantly even with constant scanning parameters and consistent task performance conditions (Liu et al., Magn. Reson. Med., 2004, 52:751-760). Reproducibility is even more of a problem when comparing fMRI signal magnitude and spatial extent of activation across scans involving different task performance levels, scan durations, pulse sequences or magnetic field strengths. In this report, the consistency of fMRI was reexamined by considering the relative spatial and temporal distribution of fMRI blood oxygen level dependent (BOLD) activation signals separately from the absolute magnitude of the activation signal in each brain area. Subjects repeatedly performed the same simple motor task but under a variety of imaging conditions, using both spiral and standard echo-planar pulse sequences and at 1.5- and 4.0-T magnetic field strengths. The results demonstrate that the absolute amplitude of BOLD statistical activation signals varied significantly across time and scanning conditions, but the relative spatial pattern of BOLD activation was highly reproducible across all conditions. Analysis of realistic simulated fMRI data sets indicates that stability of relative activation patterns could provide a useful tool for assessing the accuracy of fMRI maps.

Purpose: To prospectively evaluate the effect of preoperative functional magnetic resonance (MR) imaging localization of language and motor areas on therapeutic decision making in patients with potentially resectable brain tumors., Materials and Methods: The Institutional Review Board approved this HIPAA-compliant study, and each patient gave written informed consent. Thirty-nine consecutive patients (19 male, 20 female; mean age, 42.2 years) referred for functional MR imaging for possible tumor resection were prospectively evaluated. A preoperative diagnosis of brain tumor was made in all patients. Sentence completion and bilateral hand squeeze tasks were used to map language and sensory motor areas. Neurosurgeons completed questionnaires regarding the proposed treatment plan before and after functional MR imaging and after surgery. They also gave confidence ratings for functional MR imaging results and estimated the effect on surgical time, extent of resection, and surgical approach. The effect of functional MR imaging on changes in treatment plan was assessed with the Wilcoxon signed rank test. Differences in confidence ratings between altered and unaltered treatment plans were assessed with the Mann-Whitney U test. The estimated influence of functional MR imaging on surgical time, extent of resection, and surgical approach was denoted with summary statistics., Results: Treatment plans before and after functional MR imaging differed in 19 patients (P < .05), with a more aggressive approach recommended after imaging in 18 patients. There were no significant differences in confidence ratings for functional MR imaging between altered and unaltered plans. Functional MR imaging resulted in reduced surgical time (estimated reduction, 15-60 minutes) in 22 patients who underwent surgery, a more aggressive resection in six, and a smaller craniotomy in two., Conclusion: Functional MR imaging enables the selection of a more aggressive therapeutic approach than might otherwise be considered because of functional risk. In certain patients, surgical time may be shortened, the extent of resection increased, and craniotomy size decreased., ((c) RSNA, 2006.)

Functional magnetic resonance imaging (fMRI) was used to compare brain activation to static facial displays versus dynamic changes in facial identity or emotional expression. Static images depicted prototypical fearful, angry and neutral expressions. Identity morphs depicted identity changes from one person to another, always with neutral expressions. Emotion morphs depicted expression changes from neutral to fear or anger, creating the illusion that the actor was 'getting scared' or 'getting angry' in real-time. Brain regions implicated in processing facial affect, including the amygdala and fusiform gyrus, showed greater responses to dynamic versus static emotional expressions, especially for fear. Identity morphs activated a dorsal fronto-cingulo-parietal circuit and additional ventral areas, including the amygdala, that also responded to the emotion morphs. Activity in the superior temporal sulcus discriminated emotion morphs from identity morphs, extending its known role in processing biologically relevant motion. The results highlight the importance of temporal cues in the neural coding of facial displays.

Background and Purpose: Alzheimer's disease is associated with progressive visuospatial dysfunction. This study used functional MR (fMR) imaging with an eye movement paradigm to investigate differences in visuospatial cognition between patients with probable Alzheimer's disease (pAD) and cognitively able elderly volunteers., Methods: Using established, although imperfect, clinical criteria, patients with pAD (n = 18) and cognitively able elderly volunteers (n = 10) were selected for study. All patients underwent echo-planar fMR imaging at 1.5 T. The visually guided saccade paradigm consisted of alternating periods (30 s) of central fixation and visually guided saccades to a target appearing randomly along the horizontal meridian. Activation maps were derived using a voxelwise t test, comparing the signal intensities between the two steady-state conditions. The activation patterns were characterized by Talairach coordinates, activation volumes, and laterality ratios (LRs)., Results: Statistically significant differences existed between the activation patterns of the patients with pAD and those of the volunteers. In contrast to the control group, a left-dominant parietal activation pattern and enhanced prefrontal cortical activation were observed in most patients with pAD., Conclusion: Within the limitations of the imperfect clinical standard of reference, the reduction in right parietal activation producing the left-dominant LR for the intraparietal sulcus may reflect the progressive dysfunction in spatial attention associated with Alzheimer's disease, considering the known parietal lobe involvement in this function and the disease. The high specificity of a positive intraparietal sulcal LR measured by fMR imaging may have a role in detecting and monitoring Alzheimer's disease.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

This study presents an integrated approach to on-line fMRI data processing that combines real-time paradigm control and real-time MR image statistical analysis with nearly real-time integration of fMRI behavioral and physiological data. The real-time paradigms involve accurate timing control of multiple independent processing streams for stimulus presentation, physiological monitoring, behavioral response recording, and scanner synchronization. The real-time image analysis provides high resolution MR image reconstruction, head motion detection, translational motion correction, and t test statistical activation maps for either block design or single-trial based paradigms. The near real-time analysis allows physiological and behavioral data collected during a paradigm to be combined with the MR time series and provides extended data filtering and statistical processing within a few minutes after the end of the scan. This integrated approach improves fMRI reliability for both clinical and research studies., (Copyright 1999 Academic Press.)

High-field (3 Tesla) functional magnetic resonance imaging (MRI) was used to investigate the cortical circuitry subserving pursuit tracking in humans and compare it to that for saccadic eye movements. Pursuit performance, relative to visual fixation, elicited activation in three areas known to contribute to eye movements in humans and in nonhuman primates: the frontal eye field, supplementary eye field, and intraparietal sulcus. It also activated three medial regions not previously identified in human neuroimaging studies of pursuit: the precuneus and the anterior and posterior cingulate cortices. All six areas were also activated during saccades. The spatial extent of activation was similar for saccades and pursuit in all but two regions: spatial extent was greater for saccades in the superior branch of the frontal eye field and greater for pursuit in posterior cingulate cortex. This set of activations for smooth pursuit parallels the network of oculomotor areas characterized in nonhuman primates and complements recent studies showing that common cortical networks subserve oculomotor functions and spatial attention in humans.

Known specialized properties of the human visual cortex have been used to investigate the role of spatial resolution on fMRI using blood oxygenation level dependent (BOLD) echo-planar MRI at 3.0 tesla. The magnitude of BOLD signal changes has been examined at low (3.1 x 3.1 x 3.0 mm3) and high (0.8 x 1.6 x 3.0 mm3) resolution using both gradient-echo and spin-echo EPI. Paradigms were designed to activate primary visual cortex (V1/V2) and more specialized areas associated with detection of color (V4) and motion (V5). Sensitivity of activation maps increased at higher resolution despite the decreased total signal intensity at the smaller voxel size, presumably from reduced partial volume averaging. The greater microvascular selectivity of high-resolution spin-echo imaging enabled distinct activation patterns sensitive to motion to be detected in V1/V2 that were not apparent with gradient-echo imaging. The spatial resolution at 3.0 tesla was constrained by the size of physiological head motion relative to the voxel dimensions rather than SNR or the hemodynamic response of BOLD contrast. The higher spatial resolution at 3.0 tesla with more selective spin-echo EPI can further refine functional mapping within the cerebral cortex.

We previously developed a reaggregate cell culture system (pellet cultures) in which retinal neuroepithelial cells proliferate and give rise to rod photoreceptor cells (rods) in vitro (Watanabe and Raff, 1990, Neuron 4:461-467). In the present study, we analyzed cell differentiation and morphogenesis in pellet cultures by using both cell-type-specific markers with immunofluorescence and electron microscopy. We demonstrated that, in addition to rods, the other major retinal cell types, including amacrine cells, bipolar cells, Müller cells, and ganglion cells were all present in the pellets, where most were able to develop from dividing precursor cells in vitro. The different cell types in the pellets became organized into two distinct structures: dark rosettes and pale rosettes. The cellular composition of these structures indicated that the dark rosettes correspond to the outer nuclear layer and the pale rosettes to the inner nuclear layer of the normal retina. Ultrastructural studies have indicated that the thin layer of neuronal processes surrounding the dark rosettes correspond to the outer plexiform layer, and the central region of the pale rosettes correspond to the inner plexiform layer of the normal retina. Other features of normal retinal development also occurred in the pellets, including programmed cell death and the formation of inner and outer rod cell segments and synapses. Thus, pellet cultures provide a convenient way to study different aspects of retinal development where one can control the size and the cellular composition of the initial reaggregate.

Naturally occurring cell death complicates the analysis of cell lineage studies by making the surviving members of a clone appear more closely related than they actually are. Here we ask how much normal cell death occurs during rat retinal development, and whether that amount of death is sufficient to confuse the analysis of cell lineage relationships. We measure total cell death in the retina by combining relative counts of dead cells with absolute measurements of total cell loss. For most cell types, but not rods, we find that half of the cells generated die during normal retinal development. We use a computer model to quantify the effects of different amounts of cell death in a simulated lineage study. The simulation indicates that 50% cell death means that clonal variability analysed after the cell death period is not necessarily a good indicator of how much variability actually occurs in the underlying lineage.

We have studied the survival requirements of developing lens epithelial cells to test the hypothesis that most cells are programmed to kill themselves unless they are continuously signaled by other cells not to do so. The lens cells survived for weeks in both explant cultures and high-density dissociated cell cultures in the absence of other cells or added serum or protein, suggesting that they do not require signals from other cell types to survive. When cultured at low density, however, they died by apoptosis, suggesting that they depend on other lens epithelial cells for their survival. Lens epithelial cells cultured at high density in agarose gels also survived for weeks, even though they were not in direct contact with one another, suggesting that they can promote one another's survival in the absence of cell-cell contact. Conditioned medium from high density cultures promoted the survival of cells cultured at low density, suggesting that lens epithelial cells support one another's survival by secreting survival factors. We show for the first time that normal cell death occurs within the anterior epithelium in the mature lens, but this death is strictly confined to the region of the anterior suture.

We have recently found that about 50% of newly formed oligodendrocytes normally die in the developing rat optic nerve. When purified oligodendrocytes or their precursors are cultured in the absence of serum or added signalling molecules, they die rapidly with the characteristics of programmed cell death. This death is prevented either by the addition of medium conditioned by cultures of their normal neighboring cells in the developing optic nerve, or by the addition of platelet-derived growth factor (PDGF) or insulin-like growth factors (IGFs). Increasing PDGF in the developing optic nerve decreases normal oligodendrocyte death by up to 90% and doubles the number of oligodendrocytes, suggesting that this normally occurring glial cell death might result from a competition for limiting amounts of survival signals. These results suggest that competition for limiting amounts of survival factors is not confined to developing neurons, and raise the possibility that a similar mechanism may be responsible for some naturally occurring cell deaths in nonneural tissues.

Dead cells are observed in many developing animal tissues, but the causes of these normal cell deaths are mostly unknown. We show that about 50% of oligodendrocytes normally die in the developing rat optic nerve, apparently as a result of a competition for limiting amounts of survival signals. Both platelet-derived growth factor and insulin-like growth factors are survival factors for newly formed oligodendrocytes and their precursors in culture. Increasing platelet-derived growth factor in the developing optic nerve decreases normal oligodendrocyte death by up to 90% and doubles the number of oligodendrocytes in 4 days. These results suggest that a requirement for survival signals is more general than previously thought and that some normal cell deaths in nonneural tissues may also reflect competition for survival factors.

A remarkable feature of nerve cells is the complex and variable pattern of their axonal and dendritic branches. Quantitative studies of a simple part of the nervous system in mammals provide evidence that neuronal geometry and innervation are regulated by long-term trophic interactions between neurons and their targets. This trophic linkage may explain how nerve cells adjust their function to the needs of bodies that vary markedly in size and form.

Axons in vertebrate peripheral nerves are ensheathed by Schwann cells. For some axons, this sheath consists of a single layer of glial cell cytoplasm and plasma membranes; for other axons, Schwann cells form multilayered myelin. Whether or not a Schwann cell makes myelin is determined by a signal from the axon, but the nature of this signal is not known. Here I show that sympathetic postganglionic axons, which are normally not myelinated, become myelinated when their calibre is increased as a result of increasing the size of the peripheral target they innervate. This result implies that axon calibre, which is known to be correlated with myelination, is in fact the crucial determinant of whether an axon becomes myelinated. Furthermore, the finding that increasing or decreasing target size causes corresponding increases or decreases in axon size indicates that axon calibre is itself regulated by retrograde signals from peripheral target tissues.

The distribution of presynaptic endings on the surfaces of autonomic ganglion cells was mapped in living mice after intravenous administration of a styryl pyridinium dye. The staining and imaging techniques did not appear to damage the ganglion cells, or the synapses on them; these procedures could therefore be repeated after an arbitrary period. Observations of the same neurons at intervals of up to 3 weeks indicate that the pattern of preganglionic terminals on many of these nerve cells gradually changes.