MR Imaging Differences in the Circle of Willis between Healthy Children and Adults.

BACKGROUND AND PURPOSE: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults. MATERIALS AND METHODS: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4-74 years of age). We compared arterial diameters measured manually and cerebral perfusion via pseudocontinuous arterial spin-labeling between children and adults. RESULTS: We found that the summed cross-sectional area of the circle of Willis is larger in children than in adults, though the effect size was smaller with T2-SPACE-based measurements than with TOF-MRA. The circle of Willis is also more symmetric in children, and nonvisualized segments occur more frequently in adults than in children. Moreover, the size and symmetry of the circle of Willis correlate with cerebral perfusion. CONCLUSIONS: Our results demonstrate that the circle of Willis is different in size and symmetry in healthy children compared with adults, likely associated with developmental changes in cerebral perfusion. Further work is needed to understand why asymmetric vasculature develops in some but not all adults.

A voxel-wise assessment of growth differences in infants developing autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

White matter microstructural abnormality in children with hydrocephalus detected by probabilistic diffusion tractography.

BACKGROUND AND PURPOSE: Hydrocephalus is a severe pathologic condition in which WM damage is a major factor associated with poor outcomes. The goal of the study was to investigate tract-based WM connectivity and DTI measurements in children with hydrocephalus by using the probabilistic diffusion tractography method. MATERIALS AND METHODS: Twelve children with hydrocephalus and 16 age-matched controls were included in the study. Probabilistic diffusion tractography was conducted to generate tract-based connectivity distribution and DTI measures for the genu of the corpus callosum and the connectivity index. Tract-based summary measurements, including the connectivity index and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity), were calculated and compared between the 2 study groups. RESULTS: Tract-based summary measurement showed a higher percentage of voxels with lower normalized connectivity index values in the WM tracts in children with hydrocephalus. In the genu of the corpus callosum, the left midsegment of the corticospinal tract, and the right midsegment of the corticospinal tract, the normalized connectivity index value in children with hydrocephalus was found to be significantly lower (P < .05, corrected). The tract-based DTI measures showed that the children with hydrocephalus had significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the genu of the corpus callosum, left midsegment of the corticospinal tract, and right midsegment of corticospinal tract and lower fractional anisotropy in the genu of the corpus callosum (P < .05, corrected). CONCLUSIONS: The analysis of WM connectivity showed that the probabilistic diffusion tractography method is a sensitive tool to detect the decreased continuity in WM tracts that are under the direct influence of mechanical distortion and increased intracranial pressure in hydrocephalus. This voxel-based connectivity method can provide quantitative information complementary to the standard DTI summary measures.

CT for pediatric, acute, minor head trauma: clinician conformity to published guidelines.

BACKGROUND AND PURPOSE: In 2001, pediatric radiologists participating in a panel discussion on CT dose reduction suggested that approximately 30% of head CT examinations were performed unnecessarily. With increasing concern regarding radiation exposure to children and imaging costs, this claim warrants objective study. The purpose of this study was to test the null hypothesis that 30% of head CT studies for clinical evaluation of children with acute, minor head trauma do not follow established clinical guidelines. MATERIALS AND METHODS: Retrospective review of 182 consecutive patients with acute, minor head trauma from February 2009 to January 2010 at a tertiary care children's hospital emergency department was performed, and clinician adherence to published clinical guidelines for children younger than 2 years and children 2-20 years of age was determined. The binomial test was used for a null hypothesis of 30% unnecessary examinations against the actual percentage of head CTs deemed unnecessary on the basis of established guidelines. Statistical testing was performed for children younger than 2 years and 2-20 years of age. RESULTS: For children younger than 2 years of age, 2 of 78 (2.6%; 95% CI, 0.5%-8.3%) and, for children 2-20 years of age, 12 of 104 (11.5%; CI, 6.4%-18.7%) did not conform to established guidelines. These percentages were significantly less than the hypothesized value of 30% (P < .001). CONCLUSIONS: Clinician conformity to published guidelines for use of head CT in acute, minor head trauma is better than suggested by a 2001 informal poll of pediatric radiologists.

Diffusion tensor imaging properties and neurobehavioral outcomes in children with hydrocephalus.

BACKGROUND AND PURPOSE: White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were the following: 1) to apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus, 2) to quantify early neuropsychological deficits, and 3) to explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. MATERIALS AND METHODS: A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, and RD, were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical, and motor skills. The correlation between the Motor Scale and DTI indices in the PLIC was analyzed. RESULTS: DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD, driven by the increased RD with statistical significance (P < .05) or trend-level significance (P = .06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (P < .05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills, and motor skills were significantly lower in children with hydrocephalus (all at P < .05). The MD and RD values in the PLIC were found to have trend-level or significant correlation with the Motor Scale (P = .057, .041, respectively). CONCLUSIONS: DTI reveals alterations in the white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.

Susceptibility-weighted imaging: a new tool in the diagnosis and evaluation of abnormalities of the vein of Galen in children.

We retrospectively identified 9 consecutive children, 3 males and 6 females (age 5.2 ± 6.3 years, range 1 day to 18 years), with known or suspected AVGs who underwent MR imaging, including SWI, at our institution between January 2007 and March 2011. On the SWI sequence, arterialized blood flow was considered to be present in the vein of Galen or its tributaries when these showed abnormal signal hyperintensity from arteriovenous shunting. SWI findings were correlated with findings from DSA studies or findings from time-of-flight or contrast-enhanced MR angiography sequences. SWI was found to accurately differentiate between high-flow and low-flow AVGs and was also useful in characterizing the arterial supply and venous drainage patterns associated with high-flow AVGs.

A pilot randomized education rehabilitation trial is feasible in sickle cell and strokes.

A randomized trial was completed to assess the feasibility of a 2-year education rehabilitation program for students with sickle cell disease and memory deficits. Eleven students were assigned to tutoring with or without memory training for 2 years. Eighty-two percent completed the program. Evidence of improvement in memory and academic achievement existed. Educational rehabilitation is a feasible strategy, but further investigation is needed to assess the benefit in a multi center trial.

The NIH MRI study of normal brain development (Objective-2): newborns, infants, toddlers, and preschoolers.

The Magn. Reson. Imaging (MRI) study of normal brain development currently conducted by the Brain Development Cooperative Group represents the most extensive MRI study of brain and behavioral development from birth through young adulthood ever conducted. This multi-center project, sponsored by four Institutes of the National Institutes of Health, uses a combined longitudinal and cross-sectional design to characterize normal, healthy brain and behavioral development. Children, ages newborn through 18-plus years of age, receive comprehensive behavioral, neurological and multimodal MRI evaluations via Objective-2 (birth through 4-years 5-months of age) and Objective-1 (4-years 6-months through 18 years of age and older). This report presents methods (e.g., neurobehavioral assessment, brain scan) and representative preliminary results (e.g., growth, behavior, brain development) for children from newborn through 4-years 5-months of age. To date, 75 participants from birth through 4-years 5-months have been successfully brain scanned during natural sleep (i.e., without sedation); most with multiple longitudinal scans (i.e., 45 children completing at least three scans, 22 completing four or more scans). Results from this younger age range will increase our knowledge and understanding of healthy brain and neurobehavioral development throughout an important, dynamic, and rapid growth period within the human life span; determine developmental associations among measures of brain, other physical characteristics, and behavior; and facilitate the development of automated, quantitative MR image analyses for neonates, infants and young children. The correlated brain MRI and neurobehavioral database will be released for use by the research and clinical communities at a future date.

A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns.

OBJECTIVE: To establish the magnitude and time course of the changes in water diffusion coefficient (D(av)) following newborn infant brain injury. METHODS: Ten newborn infants at high risk for perinatal brain injury were recruited from the neonatal intensive care unit. Conventional and diffusion tensor MRI was performed on three occasions during the first week of life. Regions of injury were determined by evaluating conventional MR images (T1, T2, fluid-attenuated inversion recovery) at 1 week after injury. D(av) values were determined for these regions for all three scans. RESULTS: D(av) values were decreased in most infants 1 day after injury, but injury was not evident or underestimated in 4 of 10 infants despite the presence of injury on conventional imaging at 1 week. By the third day, D(av) values were decreased in injured areas in all infants, reaching a nadir of approximately 35% less than normal values. By the seventh day after injury, D(av) values were returning to normal (pseudonormalization). CONCLUSIONS: MR diffusion images (for which contrast is determined by changes in D(av)) obtained on the first day after injury do not necessarily show the full extent of ultimate injury in newborn infants. Images obtained between the second and fourth days of life reliably indicate the extent of injury. By the seventh day, diffusion MR is less sensitive to perinatal brain injury than conventional MR because of transient pseudonormalization of D(av). Overall, diffusion MR may not be suitable as a gold standard for detection of brain injury during the first day after injury in newborn infants.

Normal brain maturation during childhood: developmental trends characterized with diffusion-tensor MR imaging.

PURPOSE: To characterize the maturational changes in water diffusion within central gray matter nuclei and central white matter pathways of the human brain by using diffusion-tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Retrospective analysis of normal MR examination findings in 153 subjects (age range, 1 day to 11 years) referred for clinical neuroimaging was performed. All studies included diffusion tensor-encoded echo-planar MR imaging. Isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) were measured in the corpus callosum, internal capsule, caudate nucleus, lentiform nucleus, and thalamus. RESULTS: exhibited biexponential decay with age in gray and white matter regions, except for monoexponential decay in the genu of the corpus callosum. There was a steep nonlinear increase of A(sigma) in white matter tracts that paralleled the time course of the decline in D. In basal ganglia, only a small linear increase in A(sigma) was observed in patients. A(sigma) changes in the thalamus were intermediate between basal ganglia and white matter structures. CONCLUSION: Changes in magnitude and anisotropy of water diffusion follow stereotypical time courses during brain development that can be empirically described with multiexponential regression models, which suggests that quantitative scalar parameters derived from diffusion-tensor MR imaging may provide clinically useful developmental milestones for brain maturity.

Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging.

OBJECTIVE: MR imaging of central nervous system (CNS) malignancies falls short of a definitive evaluation. Tissue diagnosis remains the gold standard. Diffusion-tensor MR imaging measures the apparent diffusion coefficient and diffusion anisotropy of water in tissue. The purpose of this study was to test the hypothesis that the apparent diffusion coefficient may improve the MR imaging evaluation of newly diagnosed CNS neoplasms. We examined the relationship between the apparent diffusion coefficient, anisotropy, and tumor cellularity in 12 pediatric patients. MATERIALS AND METHODS: On the basis of histopathologic evaluation, tumors in this case series were segregated into three types: low-grade gliomas, embryonal tumors, and nonembryonal high-grade tumors. Mean apparent diffusion coefficient and anisotropy values obtained from the solid components of each tumor were compared with cellularity, total cellular area, and total nuclear area derived from biopsy material. RESULTS: The apparent diffusion coefficient ratio (tumor to normal brain) correlated well with tumor classification (p = 0.001). Anisotropy was decreased similarly in all tumor classifications. The absolute apparent diffusion coefficient correlated well with cellularity (p = 0.014) and total nuclear area (p = 0.005) per high-power field. The correlation between apparent diffusion coefficient and total cellular area per high-power field was not statistically significant. CONCLUSION: The apparent diffusion coefficient may be predictive of tumor classification and may be a useful tool in characterizing tumor cellularity and total nuclear area. These parameters are not available in standard MR imaging. Therefore, diffusion-tensor imaging may enhance the diagnostic process in pediatric CNS malignancies.

Principles and applications of echo-planar imaging: a review for the general radiologist.

Echo-planar imaging is a very fast magnetic resonance (MR) imaging technique capable of acquiring an entire MR image in only a fraction of a second. In single-shot echo-planar imaging, all the spatial-encoding data of an image can be obtained after a single radio-frequency excitation. Multishot echo-planar imaging results in high-quality images comparable to conventional MR images. However, echo-planar imaging offers major advantages over conventional MR imaging, including reduced imaging time, decreased motion artifact, and the ability to image rapid physiologic processes of the human body. The use of echo-planar imaging has already resulted in significant advances in clinical diagnosis and scientific investigation, such as in evaluation of stroke and functional imaging of the human brain, respectively. The clinical indications for echo-planar imaging are expanding rapidly, and it can now be applied to many parts of the body, including the brain, abdomen, and heart. Today, with the availability of echo-planar imaging-capable MR imagers at many sites, the general radiologist can benefit from echo-planar imaging and its clinical applications.

Reversible posterior leukoencephalopathy syndrome: evaluation with diffusion-tensor MR imaging.

PURPOSE: To characterize the changes in brain water diffusion caused by reversible posterior leukoencephalopathy syndrome (RPLS). MATERIALS AND METHODS: Twelve patients with the clinical features and conventional magnetic resonance (MR) imaging findings of RPLS underwent diffusion-tensor echo-planar MR imaging. The isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) were measured in posterior regions of diffusion abnormality and in anterior areas of normal-appearing brain. RESULTS: Across all 12 subjects, the mean D of (1.09 +/- 0.13 [SD]) x 10(-3) mm(2)/sec in affected posterior regions was 26% greater than its value of (0.87 +/- 0.07) x 10(-3) mm(2)/sec in normal-appearing anterior regions. The mean A(sigma) of 0.15 +/- 0.03 in posterior regions was 35% less than its value of 0.23 +/- 0.02 in anterior regions (t(11) = 9.58; P <.001). There was a significant inverse correlation between D and A(sigma) in posterior regions (r = -0.67; P <.018) but not in anterior regions (r = -0.12; P =.719). A follow-up study performed in one patient after resolution of symptoms documented reversal of elevated isotropic diffusion and at least partial recovery of anisotropy loss. CONCLUSION: The increased magnitude of brain water diffusion characteristic of RPLS is accompanied by reduced A(sigma). The magnitudes of these two effects are correlated and may be reversible. These observations support the proposal that vasogenic edema due to cerebrovascular autoregulatory dysfunction is the underlying pathophysiologic mechanism in uncomplicated RPLS.

Differences between gray matter and white matter water diffusion in stroke: diffusion-tensor MR imaging in 12 patients.

PURPOSE: To investigate differences in water diffusion between white matter and gray matter in acute to early subacute stroke with diffusion-tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twelve patients with unilateral middle cerebral arterial infarcts were examined with diffusion tensor-encoded echo-planar MR imaging 17 hours to 5 days after stroke onset. Isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) images were computed. (D) values were measured in ischemic and contralateral gray matter and white matter by using A(sigma) images to differentiate white matter from gray matter. (D) images were compared with unidirectional and directionally averaged diffusion-weighted images. RESULTS: In all patients, (D) images showed two distinct levels of diffusion reduction in the infarct; more severe reduction occurred exclusively in white matter. (D) values were significantly less in infarcted white matter than in infarcted gray matter, whereas (D) values in the contralateral white matter and gray matter were not significantly different. Relative to the contralateral side, (D) values in the infarct were reduced by 46% in white matter and by 31% in gray matter (P <.001). Diffusion-weighted imaging caused underestimation of the magnitude and, in some cases, the spatial extent of the white matter diffusion abnormality. CONCLUSION: Isotropic diffusion is more reduced in white matter than in gray matter in acute to early subacute middle cerebral arterial stroke. Diffusion-tensor imaging may be more sensitive than diffusion-weighted imaging to white matter ischemia.

Quantitative diffusion-tensor anisotropy brain MR imaging: normative human data and anatomic analysis.

PURPOSE: To obtain normative human cerebral data and evaluate the anatomic information in quantitative diffusion anisotropy magnetic resonance (MR) imaging. MATERIALS AND METHODS: Quantitative diffusion anisotropy MR images were obtained in 13 healthy adults by using single-shot echo-planar MR imaging and a combination of tetrahedral and orthogonal gradient encoding (whole-brain coverage in about 1 minute). White matter (WM) anatomy was assessed at visual inspection, and values were measured in various brain regions. Different anisotropy measures, including total anisotropy (A sigma), were compared on the basis of information content, rotational invariance, and susceptibility to noise. Partial volume and noise effects were simulated. RESULTS: Anisotropy MR images depicted WM features not typically seen on conventional MR images (e.g., external capsule, thalamic substructures, basal ganglia, occipital WM, thickness of the internal capsule). Statistically significant anisotropy differences occurred across brain regions, which were reproducible within and across subjects. A sigma was highest in commissural WM and progressively lower in projection and association WM. This order paralleled that of known resistance to spread of vasogenic edema, which suggested that anisotropy may be sensitive to WM histologic structure. Gray matter (GM) A sigma data were consistent with zero anisotropy, and partial volume WM-GM effects were approximately linear. A sigma image quality could be effectively improved by means of averaging. CONCLUSION: Quantitative diffusion anisotropy images can be obtained rapidly and demonstrate subtle WM anatomy. Different histologic types of WM have significant and reproducible anisotropy differences.

Tracking neuronal fiber pathways in the living human brain.

Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109-110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.

Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging.

PURPOSE: To establish quantitative standards for the directionally averaged water apparent diffusion coefficient (D) and quantitative diffusion anisotropy (A sigma) of normal brains in newborns by using diffusion tensor magnetic resonance (MR) imaging. MATERIALS AND METHODS: Diffusion tensor MR imaging was performed during the first 36 hours of life in 22 newborns (gestational age range, 31-41 weeks). Values of D and A sigma were measured in regions of interest chosen in the cortical gray matter, centrum semiovale, caudate nuclei, lentiform nuclei, thalami, internal capsules, and cerebellar hemispheres. RESULTS: The D values in the gray and white matter in newborns are considerably higher than those in adults. There is a striking correlation between gestational age and D, with D decreasing as gestational age increases. The A sigma values in the white matter in newborns are lower than those in adults. Values of A sigma show statistically significant correlations with gestational age only in the white matter of the centrum semiovale, in which A sigma values increase sharply near term. CONCLUSION: The D values primarily reflect overall brain water content. The A sigma values are more sensitive to tissue microstructure (e.g., white matter packing and myelination). The D and A sigma images reveal information and not apparent on T1- and T2-weighted images.

Functional MRI studies of word-stem completion: reliability across laboratories and comparison to blood flow imaging with PET.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated.