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Spatiotemporal wavelet resampling for functional neuroimaging data.

The study of dynamic interdependences between brain regions is currently a very active research field. For any connectivity study, it is important to determine whether correlations between two selected brain regions are statistically significant or only chance effects due to non-specific correlations present throughout the data. In this report, we present a wavelet-based non-parametric technique for testing the null hypothesis that the correlations are typical of the data set and not unique to the regions of interest. This is achieved through spatiotemporal resampling of the data in the wavelet domain. Two functional MRI data sets were analysed: (1) Data from 8 healthy human subjects viewing a checkerboard image, and (2) "Null" data obtained from 3 healthy human subjects, resting with eyes closed. It was demonstrated that constrained resampling of the data in the wavelet domain allows construction of bootstrapped data with four essential properties: (1) Spatial and temporal correlations within and between slices are preserved, (2) The irregular geometry of the intracranial images is maintained, (3) There is adequate type I error control, and (4) Expected experiment-induced correlations are identified. The limitations and possible extensions of the proposed technique are discussed.

Adult↗

A new approach to neuroimaging with magnetoencephalography.

We discuss the application of beamforming techniques to the field of magnetoencephalography (MEG). We argue that beamformers have given us an insight into the dynamics of oscillatory changes across the cortex not explored previously with traditional analysis techniques that rely on averaged evoked responses. We review several experiments that have used beamformers, with special emphasis on those in which the results have been compared to those observed in functional magnetic resonance imaging (fMRI) and on those studying induced phenomena. We suggest that the success of the beamformer technique, despite the assumption that there are no linear interactions between the mesoscopic local field potentials across distinct cortical areas, may tell us something of the balance between functional integration and segregation in the human brain. What is more, MEG beamformer analysis facilitates the study of these complex interactions within cortical networks that are involved in both sensory-motor and cognitive processes.

Algorithms↗

Meta-analysis of neuroimaging studies of the Wisconsin card-sorting task and component processes.

A quantitative meta-analysis using the activation likelihood estimation (ALE) method was used to investigate the brain basis of the Wisconsin Card-Sorting Task (WCST) and two hypothesized component processes, task switching and response suppression. All three meta-analyses revealed distributed frontoparietal activation patterns consistent with the status of the WCST as an attention-demanding executive task. The WCST was associated with extensive bilateral clusters of reliable cross-study activity in the lateral prefrontal cortex, anterior cingulate cortex, and inferior parietal lobule. Task switching revealed a similar, although less robust, frontoparietal pattern with additional clusters of activity in the opercular region of the ventral prefrontal cortex, bilaterally. Response-suppression tasks, represented by studies of the go/no-go paradigm, showed a large and highly right-lateralized region of activity in the right prefrontal cortex. The activation patterns are interpreted as reflecting a neural fractionation of the cognitive components that must be integrated during the performance of the WCST.

Brain↗

Stuttered and fluent speech production: an ALE meta-analysis of functional neuroimaging studies.

This study reports an activation likelihood estimation (ALE) meta-analysis of imaging studies of chronic developmental stuttering in adults. Two parallel meta-analyses were carried out: (1) stuttered production in the stutterers; (2) fluent production in the control subjects. The control subjects' data replicated previous analyses of single-word reading, identifying activation in primary motor cortex, premotor cortex, supplementary motor area, Rolandic operculum, lateral cerebellum, and auditory areas, among others. The stuttering subjects' analysis showed that similar brain areas are involved in stuttered speech as in fluent speech, but with some important differences. Motor areas were over-activated in stuttering, including primary motor cortex, supplementary motor area, cingulate motor area, and cerebellar vermis. Frontal operculum, Rolandic operculum, and anterior insula showed anomalous right-laterality in stutterers. Auditory activations, due to hearing one's own speech, were essentially undetectable in stutterers. The phenomenon of efference copy is proposed as a unifying account of the pattern activation revealed within this ALE meta-analysis. This provides the basis for a stuttering system model that is testable and should help to advance the understanding and treatment of this disorder.

Brain↗

Neuroimaging H.M.: a 10-year follow-up examination.

In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient H.M.'s surgical resection, based on a comprehensive analysis of magnetic resonance imaging (MRI) scans collected in 1992 and 1993 (Corkin et al. (1997) J Neurosci 17:3964-3979). We subsequently scanned H.M. on several occasions, employing more advanced data acquisition and analysis methods, and now describe additional details about his brain anatomy and pathology. This account combines results from high-resolution T1-weighted scans, which provide measures of cortical and subcortical morphometry, diffusion tensor images, which provide quantitative information about white matter microstructure and the anatomy of major fasciculi, and T2-weighted images, which highlight damage to deep white matter. We applied new MRI analysis techniques to these scans to assess the integrity of areas throughout H.M.'s brain. We documented a number of new changes, including cortical thinning, atrophy of deep gray matter structures, and a large volume of abnormal white matter and deep gray matter signal. Most of these alterations were not apparent in his prior scans, suggesting that they are of recent origin. Advanced age and hypertension likely contributed to these new findings.

Aged↗

Discovery and disclosure of incidental findings in neuroimaging research.

PURPOSE: To examine different protocols for handling incidental findings on brain research MRIs, and provide a platform for establishing formal discussions of related ethical and policy issues. MATERIALS AND METHODS: Corresponding authors identified from a database of peer-reviewed publications in 1991-2002 involving functional MRI (fMRI), alone or in combination with other imaging modalities, were invited to participate in this web-based survey. The survey asked questions regarding knowledge and handling of incidental findings, as well as characteristics of the scanning environment, training required, IRB protocol requirements, and neuroradiologist involvement. RESULTS: Seventy-four investigators who conduct MRI studies in the United States and abroad responded. Eighty-two percent (54/66) reported discovering incidental findings in their studies, such as arteriovenous malformations, brain tumors, and developmental abnormalities. Substantial variability was found in the procedures for handling and communicating findings to subjects, neuroradiologist involvement, personnel permitted to operate equipment, and training. CONCLUSION: Guidelines for minimum and optimum standards for detecting and communicating incidental findings on brain MRI research are needed.

Biomedical Research↗

Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study.

We report on a patient with adult-onset Niemann-Pick type C (NPC) disease, carrying the mutations P1007 and I1061T in the NPC1 gene, presenting with marked psychiatric changes followed by dystonia and cognitive impairment. Filipin staining, single photon emission computed tomography perfusional, positron emission tomography metabolic, conventional magnetic resonance imaging, and magnetic resonance spectroscopy findings suggested a pathophysiological correlation with phenotype expression. This case expands the clinical and genetic spectrum of the rare adult-onset NPC disease phenotype.

Adult↗

Discrimination of large venous vessels in time-course spiral blood-oxygen-level-dependent magnetic-resonance functional neuroimaging.

A technique is described for discriminating blood-oxygen-level-dependent (BOLD) signal changes originating from large venous vessels and those that arise from the cortical parenchyma based on examining the temporal delay of each pixel's response. Photic stimulation experiments were performed with a conventional 1.5 T scanner and correlated each pixel's time-course with sine and cosine functions at the frequency of the stimulus. It was found that the signal in pixels anatomically associated with gray matter was delayed between 4 and 8 s compared with the stimulus, whereas the signal in pixels correlated with visible vessels and sulci was generally delayed from 8 to 14 s. This larger delay is consistent with the longer time required for blood to reach the larger vessels. Finally, stimulus-induced NMR phase changes were observed for the largest vessels, which are attributed to bulk susceptibility shifts.

Brain↗

Mitigation of susceptibility-induced signal loss in neuroimaging using localized shim coils.

Correction of magnetic field distortions is essential for obtaining accurate brain blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) activation maps. The present work introduces an active shimming method that utilizes the magnetic field generated by resistive shim coils placed in the mouth to locally homogenize the magnetic field in the inferior portion of the frontal lobe, where the field is most seriously distorted. The shimming field can be optimized in situ patient by patient for the region of interest of the scanner operator's choice. The method at 1.5 T is shown to be effective in reducing field inhomogeneity and in recovery of fMRI signal. For example, in a region of interest approximately of 149 cm3, a coil of simple geometry can reduce the root mean square of the magnetic field by more than 50% and the recovered signal increases the extent of activation detected in a breath-holding fMRI experiment.

Artifacts↗

Deaf poor readers' pattern reversal visual evoked potentials suggest magnocellular system deficits: implications for diagnostic neuroimaging of dyslexia in deaf individuals.

Deafness and developmental dyslexia in the same individual may jointly limit the acquisition of reading skills for different underlying reasons. A diagnostic marker for dyslexia in deaf individuals must therefore detect the presence of a neurobiologically based dyslexia but be insensitive to the ordinary developmental influences of deafness on reading skill development. We propose that the functional status of the magnocellular visual system in deaf individuals is potentially such a marker. We present visual evoked potential (VEP) evidence that adult deaf poor readers as a group display magnocellular system deficits not observed in deaf good readers. We recorded pattern-reversal VEPs to high- and low-contrast checkerboard stimuli, which primarily activate the parvocellular and magnocellular pathways, respectively. Principal components analysis of these VEPs produced a time-ordered sequence of three early components that displayed interactions between reading skill and stimulus contrast across multiple scalp recording sites. Deaf poor readers displayed an abnormal absence of contrast-sensitive VEP responses at occipital sites during early visual processing (75 ms poststimulus), whereas deaf good readers showed the expected early contrast-sensitive occipital VEP responses. Over the subsequent 225 ms, the occipital VEP behavior of deaf poor readers closely approximated that of deaf good readers. The VEPs of deaf poor readers were apparently characterized by delayed responses to low-contrast stimuli compared with deaf good readers. Our results provide the first neurobiological evidence that developmental dyslexia exists within the deaf population and is associated with the same underlying magnocellular system deficit that has been observed in hearing dyslexics. Direct neural imaging of the status of the magnocellular visual system in deaf individuals may eventually provide differential diagnosis of developmental dyslexia in the deaf population.

Adult↗

AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.

A package of computer programs for analysis and visualization of three-dimensional human brain functional magnetic resonance imaging (FMRI) results is described. The software can color overlay neural activation maps onto higher resolution anatomical scans. Slices in each cardinal plane can be viewed simultaneously. Manual placement of markers on anatomical landmarks allows transformation of anatomical and functional scans into stereotaxic (Talairach-Tournoux) coordinates. The techniques for automatically generating transformed functional data sets from manually labeled anatomical data sets are described. Facilities are provided for several types of statistical analyses of multiple 3D functional data sets. The programs are written in ANSI C and Motif 1.2 to run on Unix workstations.

Brain↗

Parametric analysis of functional neuroimages: application to a variable-rate motor task.

Positron emission tomography (PET) has proven to be a powerful tool in identifying the functional neuroanatomy underlying cognitive and sensorimotor processing. In this paper, we present a method for mathematically modeling the changes in regional cerebral blood flow (rCBF) as a function of experimental parameters using step and linear functions. PET was used to measure rCBF in six subjects who tracked a target moving with constant amplitude across a computer screen at four different frequencies. Each subject tracked the target by flexing and extending the wrist. Two scans were performed at each frequency. The data for each subject were normalized by the mean blood flow in each scan and scaled to the mean blood flow at rest. Scaled rCBF was regressed onto movement frequency to identify voxels which had either a significant linear or step function response to the frequency of movement. A group analysis was also performed to identify significant functional changes common to all subjects. Significant rCBF increases in relation to movement frequency were found in the supplementary motor area, primary motor cortex, premotor cortex, thalamus, and cerebellum and localized using the Talairach atlas. Habituation of responses was not observed.

Adult↗

Functional magnetic resonance neuroimaging data acquisition techniques.

Functional MRI studies of human brain require rapid data acquisition techniques, to map dynamic changes with sufficient anatomical coverage. In addition, task activation studies employing functional MRI require a high scan sensitivity, in order to discriminate the small, activation-related signal changes from background noise. An overview is given of current fast scan methods, which are sensitized to detect susceptibility changes related to task-induced changes in blood oxygenation. Sources of artifacts are discussed, as well as their effect on image quality.

Artifacts↗

Psychophysiological and modulatory interactions in neuroimaging.

In this paper we introduce the idea of explaining responses, in one cortical area, in terms of an interaction between the influence of another area and some experimental (sensory or task-related) parameter. We refer to these effects as psychophysiological interactions and relate them to interactions based solely on experimental factors (i.e., psychological interactions), in factorial designs, and interactions among neurophysiological measurements (i.e., physiological interactions). We have framed psychophysiological interactions in terms of functional integration by noting that the degree to which the activity in one area can be predicted, on the basis of activity in another, corresponds to the contribution of the second to the first, where this contribution can be related to effective connectivity. A psychophysiological interaction means that the contribution of one area to another changes significantly with the experimental or psychological context. Alternatively these interactions can be thought of as a contribution-dependent change in regional responses to an experimental or psychological factor. In other words the contribution can be thought of as modulating the responses elicited by a particular stimulus or psychological process. The potential importance of this approach lies in (i) conferring a degree of functional specificity on this aspect of effective connectivity and (ii) providing a model of modulation, where the contribution from a distal area can be considered to modulate responses to the psychological or stimulus-specific factor defining the interaction. Although distinct in neurobiological terms, these are equivalent perspectives on the same underlying interaction. We illustrate these points using a functional magnetic resonance imaging study of attention to visual motion and a position emission tomography study of visual priming. We focus on interactions among extrastriate, inferotemporal, and posterior parietal regions during visual processing, under different attentional and perceptual conditions.

Attention↗

Functional clustering: identifying strongly interactive brain regions in neuroimaging data.

Brain imaging data are generally used to determine which brain regions are most active in an experimental paradigm or in a group of subjects. Theoretical considerations suggest that it would also be of interest to know which set of brain regions are most interactive in a given task or group of subjects. A subset of regions that are much more strongly interactive among themselves than with the rest of the brain is called here a functional cluster. Functional clustering can be assessed by calculating for each subset of brain regions a measure, the cluster index, obtained by dividing the statistical dependence within the subset by that between the subset and rest of the brain. A cluster index value near 1 indicates a homogeneous system, while a high cluster index indicates that a subset of brain regions forms a distinct functional cluster. Within a functional cluster, individual brain regions are ranked at the center or at the periphery according to their statistical dependence with the rest of that cluster. The applicability of this approach has been tested on PET data obtained from normal and schizophrenic subjects performing a set of cognitive tasks. Analysis of the data reveals evidence of functional clustering. A comparative evaluation of which regions are more peripheral or more central suggests distinct differences between the two groups of subjects. We consider the applicability of this analysis to data obtained with imaging modalities offering higher temporal resolution than PET.

Adult↗