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Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs.

A major attraction of voxel-based morphometry (VBM) is that it allows researchers to explore large datasets with minimal human intervention. However, the validity and sensitivity of the Statistical Parametric Mapping (SPM2) approach to VBM are the subject of considerable debate. We visually inspected the SPM2 gray matter segmentations for 101 research participants and found a gross inclusion of non-brain tissue surrounding the entire brain as gray matter in five subjects and focal areas bordering the brain in which non-brain tissue was classified as gray matter in many other subjects. We also found many areas in which the cortical gray matter was incorrectly excluded from the segmentation of the brain. The major source of these errors was the misregistration of individual brain images with the reference T1-weighted brain template. These errors could be eliminated if SPM2 operated on images from which non-brain tissues (scalp, skull, and meninges) are removed (brain-extracted images). We developed a modified SPM2 processing pipeline that used brain-extracted images as inputs to test this hypothesis. We describe the modifications to the SPM2 pipeline that allow analysis of brain-extracted inputs. Using brain-extracted inputs eliminated the non-brain matter inclusions and the cortical gray matter exclusions noted above, reducing the residual mean square errors (RMSEs, the error term of the SPM2 statistical analyses) by over 30%. We show how this reduction in the RMSEs profoundly affects power analyses. SPM2 analyses of brain-extracted images may require sample sizes only half as great as analyses of non-brain-extracted images.

Adult↗

Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: Inverse relationships during postadolescent brain maturation.

Recent in vivo structural imaging studies have shown spatial and temporal patterns of brain maturation between childhood, adolescence, and young adulthood that are generally consistent with postmortem studies of cellular maturational events such as increased myelination and synaptic pruning. In this study, we conducted detailed spatial and temporal analyses of growth and gray matter density at the cortical surface of the brain in a group of 35 normally developing children, adolescents, and young adults. To accomplish this, we used high-resolution magnetic resonance imaging and novel computational image analysis techniques. For the first time, in this report we have mapped the continued postadolescent brain growth that occurs primarily in the dorsal aspects of the frontal lobe bilaterally and in the posterior temporo-occipital junction bilaterally. Notably, maps of the spatial distribution of postadolescent cortical gray matter density reduction are highly consistent with maps of the spatial distribution of postadolescent brain growth, showing an inverse relationship between cortical gray matter density reduction and brain growth primarily in the superior frontal regions that control executive cognitive functioning. Inverse relationships are not as robust in the posterior temporo-occipital junction where gray matter density reduction is much less prominent despite late brain growth in these regions between adolescence and adulthood. Overall brain growth is not significant between childhood and adolescence, but close spatial relationships between gray matter density reduction and brain growth are observed in the dorsal parietal and frontal cortex. These results suggest that progressive cellular maturational events, such as increased myelination, may play as prominent a role during the postadolescent years as regressive events, such as synaptic pruning, in determining the ultimate density of mature frontal lobe cortical gray matter.

Adolescent↗

Thalamocortical dysrhythmia and the thalamic reticular nucleus in behaving rats.

OBJECTIVES: The aim of this study was to investigate the effects of bilateral chemical lesion of the rostral pole of the thalamic reticular nucleus on EEG activities in freely moving rats applying quantitative analysis and brain mapping of power spectra distribution. METHODS: Ketamine-sedated Sprague-Dawley rats were implanted to monitor behavioral states with frontoparietal electrodes in a first series of experiments and with multiple electrodes along the antero-posterior axis (F1, F2, F7, F8, T3, T4, P3, P4) in a second series. Monopolar and bipolar recordings were obtained in animals stereotaxically injected with ibotenic acid into both rostral poles of the thalamic reticular nucleus. Long-term video-EEG recordings and brain mapping based on quantitative spectral analysis were made. RESULTS: Two forms of dysrhythmia gradually emerged in the neocortical EEG at 12-24h post-injection: potentiation of theta waves and spontaneous high-voltage spindles (HVS) at 4.5-8Hz frequency. Brain mapping during these dysrhythmia shows highest power posteriorly (parietotemporal) for theta and mesiofrontally for HVS. CONCLUSIONS: Given the lack of inhibitory intrinsic interneurons in the rat thalamus, bilateral destruction of a small part of the solely GABAergic population may promote cortical dysrhythmia (probably by dis-inhibition). The topographic differences in power might indicate different involved structures.

Anesthetics, Dissociative↗

Three-dimensional mapping of brain neuropils in the cockroach, Diploptera punctata.

Herein, we present a complete three-dimensional (3D) map of major neuropil structures in the central brain of the cockroach Diploptera punctata. The positions of the structures have been ascertained by confocal microscopy, which, until now-for reasons of tissue opacity and nonhomogeneity-has been thought impractical in imaging fluorescently labeled structures thicker than 150 microm. In this report, however, we have used digestive enzymes and microwave-aided fixation to stain, clear, and optically section, in its entirety, an intact central brain more than 500 microm thick. The central brain from an adult female cockroach was stained thoroughly with the membrane probe NBD-ceramide and the DNA probe propidium iodide. The central brain as well as such neuropil regions as mushroom bodies, central complex, antennal glomeruli, and lobus glomerulati were individually outlined, segmented, and reconstructed in three dimensions to a spatial resolution of approximately 1 microm in the X-Y plane and 3 microm in the Z plane. The volume and surface area of each neuropil compartment were determined, and Kenyon cells of the mushroom bodies were counted. We determined that each brain hemisphere contains about 230,000 Kenyon cells, 99 antennal lobe glomeruli, and 40 lobus glomerulatus glomeruli. Segmented compartments were assigned as separate channels and merged into a single data base to reconstruct a 3D central brain containing eight different channels. This is the first 3D map at submicron resolution of an entire animal's brain that measures more than 500 microm in thickness.

Animals↗

[The mapping of brain biopotentials during the solving of a verbal task].

Reverse averaging of cortical potentials from the moment of the motor response followed the verbal task solving (anagram riddle) revealed some brain potentials correlations with the process of a decision making. In the case of task solving the negative frontal wave with the latency 900-400 ms from the motor response was recorded. Intracortical interaction mapping of this potential showed the regular patterns of cortical functional connections in different frequency ranges (alpha, beta). Successful solving of the task was characterized with predominant interaction foci topography in the frontal and left-temporal cortical areas in alpha band and parietal zones in beta. The absence of the task solution was characterized with the parieto-occipital interaction foci in alpha band and their frontal localization in beta.

Adolescent↗

[Intraoperative electrical cortical stimulation in cerebral lesions].

INTRODUCTION: Intraoperative brain mapping is used during neurosurgery in functional cortex to facilitate the extent of cortical resection and to identify nonfunctional tissue to remove subcortical lesions. OBJECTIVE: To describe the intraoperative brain mapping protocol that has been utilized in the Hospital Clínico San Carlos of Madrid, Spain. Detailed somatotopic motor, sensitive and language localization is possible using direct cortical electric stimulation in the awake patient. CONCLUSIONS: Intraoperative brain mapping is a surgical adjunct used during lesionectomy in functional cortex. In addition to preserving functions, the other essential goal is to achieve a radical removal while attempting to minimize the associated morbidity.

Brain Diseases↗

Three-dimensional in vivo mapping of brain lesions in humans.

We describe a multistep technique for three-dimensional reconstruction and analysis of brain lesions in vivo, based on the manipulation of magnetic resonance raw data obtained with a special protocol. The technique permits the direct visual identification of neuroanatomical landmarks in each brain specimen and eliminates the need to rely on averaged templates of human brain sections, which can be a source of lesion localization error. The technique also allows for the bidirectional cross-reference between data points in two-dimensional slices and in volume reconstruction and for the projection of subcortical structures onto the three-dimensional cortical surface. The three-dimensional lesion mapping technique can be applied to research with the lesion method in both human and nonhuman primates, to the planning of neurosurgical lesion approach, and to the teaching of neuroanatomy.

Brain Diseases↗

A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory.

Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during a graded auditory-verbal memory task. Subjects were required to remember and then immediately, and freely, recall a series of auditorily presented word lists varying from two to 13 words in length. Significant regional correlations between rCBF and memory load (word list length) were identified using statistical parametric mapping. Increasing memory load correlated with increasing rCBF in the cerebellar vermis and hemispheres, thalamus bilaterally, the superior and middle frontal gyri bilaterally, anterior insular regions bilaterally, anterior cingulate, precuneus and left and right lateral premotor areas. Increasing memory load also correlated with decreasing rCBF in the left and right superior temporal/insular regions, medial frontal gyrus, Brodmann's area 37 bilaterally, cuneus, inferior parietal lobule bilaterally and the mid-portion of the cingulate cortex. The pattern of rCBF change closely resembled that identified in a previously reported study using a cognitive subtraction paradigm and provides further evidence for a widespread neural system subserving auditory-verbal memory. The patterns of rCBF response suggest that the areas identified are associated with limited capacity processes for encoding and retrieval.

Adult↗

Enhanced detection in brain activation maps using a multifiltering approach.

Current methods for detecting activation foci in positron emission tomography difference images include a low pass filtering step aimed at improving the signal-to-noise ratio. However, we show that detection sensitivity depends both on the activation signal and the filter sizes. Therefore, we propose to improve current detection methods by using a multifiltering strategy that is shown to be more sensitive when various kinds of signals are present in the brain activation images.

Brain↗

Rapid and automatic localization of the anterior and posterior commissure point landmarks in MR volumetric neuroimages.

RATIONALE AND OBJECTIVE: Accurate identification of the anterior commissure (AC) and posterior commissure (PC) is critical in neuroradiology, functional neurosurgery, human brain mapping, and neuroscience research. Moreover, major stereotactic brain atlases are based on the AC and PC. Our goal is to provide an algorithm for a rapid, robust, accurate and automatic identification of AC and PC. MATERIALS AND METHOD: The method exploits anatomical and radiological properties of AC, PC and surrounding structures, including morphological variability. The localization is done in two stages: coarse and fine. The coarse stage locates the AC and PC on the midsagittal plane by analyzing their relationships with the corpus callosum, fornix, and brainstem. The fine stage refines the AC and PC in a well-defined volume of interest, analyzing locations of lateral and third ventricles, interhemispheric fissure, and massa intermedia. RESULTS: The algorithm was developed using simple operations, like histogramming, thresholding, region growing, 1D projections. It was tested on 94 diversified T1W and SPGR datasets. After the fine stage, 71 (76%) volumes had an error between 0-1 mm for the AC and 55 (59%) for the PC. The mean errors were 1.0 mm (AC) and 1.0 mm (PC). The accuracy has improved twice due to fine stage processing. The algorithm took about 1 second for coarse and 4 seconds for fine processing on P4, 2.5 GHz. CONCLUSION: The use of anatomical and radiological knowledge including variability in algorithm formulation aids in localization of structures more accurately and robustly. This fully automatic algorithm is potentially useful in clinical setting and for research.

Algorithms↗

Statistical parametric mapping of brain SPECT perfusion abnormalities in patients with Alzheimer's disease.

Brain perfusion in 20 patients with mild Alzheimer's disease (AD), 20 patients with moderate AD and 20 control subjects (matched for age, gender and education) were assessed by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO). SPECT images were transformed to a standard size and shape for group comparisons by the voxel-based t test of the statistical parametric mapping techniques. Cerebral hypoperfusion in the left lower parietal area was found in mild AD patients. In moderate AD patients, significant cerebral hypoperfusion was located in bilateral posterior parietotemporal cortices, contiguous anterior occipital lobes, posterior cingulate gyri and, to a lesser extent, in frontal areas.

Aged↗

Modified Talairach landmarks.

BACKGROUND: Brain atlas-assisted operations, such as targeting in stereotactic and functional neurosurgery, localisation analysis and metanalysis in human brain mapping, or structure segmentation and labelling in neuroradiology, highly depend on the accurate localisation of the landmarks used for atlas-to-data registration. One of practical and widely used registration methods is the Talairach proportional grid system transformation based on the Talairach landmarks. However, there are several problems associated with the original Talairach landmarks. In the Talairach-Tournoux brain atlas, some Talairach landmarks are not available and locations of others contradict their definitions. When dealing with patient-specific data, the definitions of the Talairach landmarks are not constructive enough or make their identification time consuming. Moreover, there is an inconsistency between the Talairach landmarks and Talairach grid. METHOD: The modified Talairach landmarks, conceptually equivalent to the original Talairach landmarks, are introduced here. They have several advantages and overcome some limitations of the original Talairach landmarks. Three various intercommissural distances are defined: central, internal, and tangential, and the formulas determining their lengths and errors associated are derived. An efficient method for calculating the modified cortical landmarks is proposed. FINDINGS: The internal intercommissural distance is the closest to the original Talairach intercommissural distance. Its relative intercommissural error is only 0.5%, as opposed to the central and tangential intercommissural distances resulting in high (about 10%) relative intercommissural errors. On the other hand, the internal and central intercommissural distances result in a high maximum displacement error at cortex amounting to about 11 mm while the tangential intercommissural distance gives only 1 mm error. The sensitivity of the internal intercommissural distance to the actual location of the intercommissural plane is high reaching above 10%. On the other hand, the sensitivity of the central intercommissural distance is below 0.5%. Each of the Talairach cortical landmarks needs three coordinates for its identification that requires the availability of two two-dimensional projections, the generation and analysis of which is computationally expensive. A modified cortical landmark is identified on a single, one-dimensional projection. INTERPRETATION: The modified Talairach landmarks facilitate the rapid and automated calculation of the Talairach transformation and give more flexibility in their use for specific applications. In stereotactic and functional neurosurgery, the internal intercommissural distance is the most suitable to provide a high accuracy for subcortical structures. In localisation analysis in human brain mapping research, a high accuracy has to be achieved at the cortex and the tangential intercommissural line is superior. Human brain mapping metanalysis may benefit from the use of the central intercommissural distance minimising errors due to the intercommissural plane positioning. In neuroradiology, a high accuracy is required both for subcortical and cortical structures and the tangential intercommissural line should be used.

Anthropometry↗

CT-CBF correlations of cognitive deficits in multi-infarct dementia.

Fifteen right-handed patients with Multi-Infarct Dementia underwent cognitive testing by the Jacobs Mini-Mental Scale (MMQ), and xenon contrast CT scanning. Local cerebral blood flow (LCBF) and local partition coefficient (L lambda) values were measured by stable xenon contrast CT scanning and potential methodological errors were discussed. Reduced values were graded: 0 = normal, 1 = mild, 2 = moderate, 3 = severe. Graded values were pooled and plotted on composite brain maps to display locations of abnormal L lambda and LCBF values. Topographic brain maps, showing most frequent locations of reduced L lambda values, confirmed the common anatomical locations of multiple cerebral infarcts to be distributed in both thalami, temporal lobes, basal ganglia, left internal capsule and right cingulate cortex. Gray matter flow values were reduced in similar cortical and subcortical regions. There were no correlations between MMQ scores and reduced LCBF values for caudate and lenticular nuclei. Direct and statistically significant correlations were found between reduced MMQ scores and mean LCBF values for left or right frontal cortex, left or right temporal cortex and left or right thalamus. Subgrouping MMQ tests according to functions assessed, indicated that left mid-temporal ischemia correlated with dyscalculia and memory disturbances while ischemia of both frontal lobes correlated with disorientation to time and place.

Aged↗

Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. II. Event-related synchronization in the gamma band.

It has been shown in animals that neuronal activity in the 'gamma band' (>30 Hz) is associated with cortical activation and may play a role in multi-regional and multi-modal integration of cortical processing. Studies of gamma activity in human scalp EEG have typically focused on event-related synchronization (ERS) in the 40 Hz band. To assess further the gamma band ERS further, as an index of cortical activation and as a tool for human functional brain mapping, we recorded subdural electrocorticographic (ECoG) signals in five clinical subjects while they performed visual-motor decision tasks designed to activate the representations of different body parts in sensorimotor cortex. ECoG spectral analysis utilized a mixed-effects analysis of variance model in which within-trial temporal dependencies were accounted for. Taking an exploratory approach, we studied gamma ERS in 10-Hz-wide bands (overlapping by 5 Hz) ranging from 30 to 100 Hz, and compared these findings with changes in the alpha (8-13 Hz) and beta (15-25 Hz) bands. Gamma ERS (observed in three out of subjects) occurred in two broad bands-'low gamma' included the 35-45 and 40-50 Hz bands, and 'high gamma' the 75-85, 80-90, 85-95 and 90-100 Hz bands. The temporal and spatial characteristics of low and high gamma ERS were distinct, suggesting relatively independent neurophysiological mechanisms. Low gamma ERS often began after onset of the motor response and was sustained through much of it, in parallel with event-related desynchronization (ERD) in the alpha band. High gamma ERS often began during, or slightly before, the motor response and was transient, ending well before completion of the motor response. These temporal differences in low and high gamma suggest different functional associations with motor performance. Compared with alpha and beta ERD, the topographical patterns of low and high gamma ERS were more discrete and somatotopically specific and only occurred over contralateral sensorimotor cortex during unilateral limb movements (alpha and beta ERD were also observed ipsilaterally). Maps of sensorimotor function inferred from gamma ERS were consistent with maps generated by cortical electrical stimulation for clinical purposes. In addition, different task conditions in one subject produced consistent differences in both motor response latencies and onset latency of gamma ERS, particularly high gamma ERS. Compared with alpha and beta ERD, the topography of gamma ERS is more consistent with traditional maps of sensorimotor functional anatomy. In addition, gamma ERS may provide complementary information about cortical neurophysiology that is useful for mapping brain function in humans.

Adult↗

In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon.

BACKGROUND AND PURPOSE: Recent reports have shown an increase in specific binding (in vitro) of [3H]PK 11195 to peripheral-type benzodiazepine receptors in both experimental animals and humans, reflecting a glial/macrophagic reaction within and around focal ischemic insults. We have evaluated by positron emission tomography the time course of changes in brain uptake in vivo of 11C-labeled PK 11195 and flumazenil (an antagonist of central benzodiazepine receptors) as indirect and direct markers of neuronal loss, respectively, after focal cerebral ischemia. METHODS: Ten anesthetized baboons were submitted to sequential positron emission tomography studies between day 1 and day 91 after unilateral middle cerebral artery occlusion. The studies consisted of successive assessments, in the same positron emission tomography session, of [11C]PK 11195, [11C]flumazenil, cerebral blood flow, and oxygen consumption; late computed tomographic scans were obtained to map the approximate contours of infarction and to define a concentric peri-infarct area. RESULTS: We found a significant time-dependent increase in [11C]PK 11195 uptake in the peri-infarcted area, maximum at 20 to 40 days after occlusion. In contrast, there was a time- and perfusion-independent significant decrease in [11C]flumazenil uptake in the infarcted area, stable from day 2 onward, and already present in one baboon at day 1. Challenge studies with saturating doses of cold ligands confirmed that these changes represented alterations in specific binding. [11C]Flumazenil uptake was not affected in hypometabolic (but apparently noninfarcted, ie, deafferented) cortical areas. CONCLUSIONS: The delayed and apparently transient increases in [11C]PK 11195 specific uptake in vivo presumably represent glial/macrophage reaction; the marked depression in [11C]flumazenil specific binding, which appears selective for synaptic damage, is both precocious and sustained and thus may be better suited for the early assessment of ischemic damage in humans.

Animals↗

Quantitative maps of GAbAergic and glutamatergic neuronal systems in the human brain.

GABAergic and glutamatergic neuronal systems in adult normal human brains were shown quantitatively and in detail through the distributions of glutamate decarboxylase (GAD) and glutamate dehydrogenase (GDH), respectively. Consecutive coronal sections containing part of the striatum and the substantia nigra were obtained from the right hemisphere of three deceased persons with no history of neurological or psychiatric diseases and were stained immunohistochemically for GAD and GDH. Each stained section was divided into approximately 3 million microareas and the immunohistochemical fluorescence intensity in each area was measured by a human brain mapping analyzer, which is a microphotometry system for analysis of the distribution of neurochemicals in a large tissue slice. In the analyzed brain regions, conspicuously intense GAD-like immunoreactivity was observed in the substantia nigra, globus pallidus, and hypothalamus. GDH was widely and rather evenly distributed in the gray matter compared to GAD, although intense GDH-like immunoreactivity was observed in the lateral geniculate nucleus and substantia nigra. Within the substantia nigra, the globus pallidus, and other regions, characteristic distributions of GAD- and GDH-like immunoreactivity were found. We believe that the analysis of the human brain by this novel technique can help to understand the functional distribution of neuronal systems in the normal human brain and may be able to identify abnormal changes in the diseased human brain. It can also provide basic data to help in the interpretation of functional magnetic resonance imaging or positron emission tomography.

Aged↗