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Neuromagnetic localization of rhythmic activity in the human brain: a comparison of three methods.

Cortical rhythmic activity is increasingly employed for characterizing human brain function. Using MEG, it is possible to localize the generators of these rhythms. Traditionally, the source locations have been estimated using sequential dipole modeling. Recently, two new methods for localizing rhythmic activity have been developed, Dynamic Imaging of Coherent Sources (DICS) and Frequency-Domain Minimum Current Estimation (MCE(FD)). With new analysis methods emerging, the researcher faces the problem of choosing an appropriate strategy. The aim of this study was to compare the performance and reliability of these three methods. The evaluation was performed using measured data from four healthy subjects, as well as with simulations of rhythmic activity. We found that the methods gave comparable results, and that all three approaches localized the principal sources of oscillatory activity very well. Dipole modeling is a very powerful tool once appropriate subsets of sensors have been selected. MCE(FD) provides simultaneous localization of sources and was found to give a good overview of the data. With DICS, it was possible to separate close-by sources that were not retrieved by the other two methods.

Alpha Rhythm↗

White matter abnormalities in autism detected through transverse relaxation time imaging.

While neuroimaging studies have reported neurobiological abnormalities in autism, the underlying tissue abnormalities remain unclear. Quantitative transverse relaxation time (T2) imaging permits the examination of tissue abnormalities in vivo, with increased T2 largely reflecting increased tissue water. Blood flow and the presence of tissue iron may also affect T2. In this study, we used voxel-based relaxometry of the cerebrum and global averages to examine T2 abnormalities in autism. Nineteen males with autism (age: 9.2 +/- 3.0 years) and 20 male controls (age: 10.7 +/- 2.9 years) underwent magnetic resonance imaging at 3.0 T. Quantitative T2 maps, generated through gradient echo sampling of the free induction decay and echo, were segmented into gray matter, white matter, and cerebrospinal fluid. Average cerebral gray and white matter T2 were determined and compared between groups. To assess localized T2 differences, the quantitative T2 maps were warped to a template created for this study, smoothed, and compared using statistical parametric mapping. Patients with autism had an increase in average cerebral white matter T2, although no group differences were seen in average cerebral gray matter T2. Patients with autism also had bilateral regional T2 increases in the gray matter and associated white matter of the parietal lobes (primary sensory association areas) and occipital lobes (visual association areas) and in the white matter within the supplementary motor areas in the frontal lobes. The regional and global elevations in white matter T2 suggest abnormalities of white matter tissue water content in autism, which may represent a neurobiological basis for the aberrant cortical connectivity hypothesized to underlie the disorder.

Adolescent↗

Identification of large-scale networks in the brain using fMRI.

Cognition is thought to result from interactions within large-scale networks of brain regions. Here, we propose a method to identify these large-scale networks using functional magnetic resonance imaging (fMRI). Regions belonging to such networks are defined as sets of strongly interacting regions, each of which showing a homogeneous temporal activity. Our method of large-scale network identification (LSNI) proceeds by first detecting functionally homogeneous regions. The networks of functional interconnections are then found by comparing the correlations among these regions against a model of the correlations in the noise. To test the LSNI method, we first evaluated its specificity and sensitivity on synthetic data sets. Then, the method was applied to four real data sets with a block-designed motor task. The LSNI method correctly recovered the regions whose temporal activity was locked to the stimulus. In addition, it detected two other main networks highly reproducible across subjects, whose activity was dominated by slow fluctuations (0-0.1 Hz). One was located in medial and dorsal regions, and mostly overlapped the "default" network of the brain at rest [Greicius, M.D., Krasnow, B., Reiss, A.L., Menon, V., 2003. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the U.S.A. 100, 253-258]; the other was composed of lateral frontal and posterior parietal regions. The LSNI method we propose allows to detect in an exploratory and systematic way all the regions and large-scale networks activated in the working brain.

Adult↗

A curvature-based approach to estimate local gyrification on the cortical surface.

Using magnetic resonance imaging and a new method to analyze local surface shape, we examined the effects of gender on gyrification in a large and well-matched sample of healthy subjects. Unlike traditional 2D methods that produce whole-brain measurements of cortical complexity or more sophisticated 3D parametric mesh-based techniques that allow only different sections (lobes) of the cortex to be investigated, we employed a novel approach with increased spatial resolution. Although our method is sensitive to similar cortical features like the classic whole-brain gyrification index (depths of sulci and heights of gyri), we are now able to provide detailed and regionally specific estimates of cortical convolution at thousands of points across the cortical surface without introducing any bias through the rater or the selected orientation of the slices. We revealed pronounced gender differences, showing increased gyrification in frontal and parietal regions in females compared to males that agree with recent regions-of-interest findings. In addition, we detected higher female gyrification in temporal and occipital cortices that was not previously identified in studies using more global measures. No cortical area was significantly more convoluted in males compared to females. Our results demonstrate the sensitivity of this automated approach for identifying very local changes in gyrification. This technique may serve to isolate regionally specific changes in fissuration/gyrification in neurodevelopmental or neuropsychiatric disorders.

Adult↗

Parallel networks operating across attentional deployment and motion processing: a multi-seed partial least squares fMRI study.

Anticipatory deployment of attention may operate through networks of brain areas that modulate the representations of to-be-attended items in advance of their occurrence through top-down control. Luks and Simpson (2004) (Luks, T.L., Simpson, G.V., 2004. Preparatory deployment of attention to motion activates higher order motion-processing brain regions. NeuroImage 22, 1515-1522) found activations in both control areas and sensory areas during anticipatory deployment of attention to visual motion in the absence of stimuli. In the present follow-up analysis, we tested which network activity during anticipatory deployment of attention is functionally connected with task-related network activity during subsequent selective processing of motion stimuli. Following a cue (anticipatory phase), participants monitored a sequence of complex motion stimuli for a target motion pattern (task phase). We analyzed fMR signal using a partial least squares analysis with previously identified cue- and motion-related voxels as seed regions. The method identified two networks that covaried with the activity of seed regions during the cue and motion-stimulus-processing phases of the task. We suggest that the first network, involving ventral intraparietal sulcus, superior parietal lobule and motor areas, is related to anticipatory and sustained visuomotor attention. Operating in parallel to this visuomotor attention network, there is a second network, involving visual occipital areas, frontal areas as well as angular and supramarginal gyri, that may underlie anticipatory and sustained visual attention processes.

Adult↗

Functional localization in the human cerebellum based on voxelwise statistical analysis: a study of 90 patients.

The aim of the present study was to examine somatotopy in the cerebellar cortex and a possible differential role of the cerebellar cortex and nuclei in functional outcome. Clinical findings and 3D MRI-based cerebellar lesions site were compared in a group of 90 patients with focal cerebellar lesion using International Cooperative Ataxia Rating Scale (ICARS) and voxel-based lesion-symptom mapping (VLSM). Separate analysis was performed in patients with acute and chronic ischemic lesions (n=43) and patients with acute and chronic surgical lesions (n=47). Thirty-eight patients were included after resection of a cerebellar tumor in childhood or adolescence. The most significant lesion symptom correlations were observed in the subgroup with acute ischemic lesions. Limb ataxia was significantly correlated with lesions of the interposed (NI) and part of the dentate nuclei (ND), ataxia of posture and gait with lesions of the fastigial nuclei (NF) including NI. Correlations with cortical lesions were less significant and present in the superior cerebellum only. Upper limb ataxia was correlated with lesions of vermal, paravermal and hemispheral lobules IV-V and VI, lower limb ataxia with lesions of vermal, paravermal and hemispheral lobules III and VI, dysarthria with lesions of paravermal and hemispheral lobules V and VI and ataxia of posture and gait with lesions of vermal and paravermal lobules II, III and IV. In the subgroups with chronic focal lesions, similar correlations were observed with lesions of the cerebellar nuclei, but significantly less correlations with lesions of the cerebellar cortex. Functional localization based on VLSM backs findings in previous animal and functional brain images studies in healthy human subjects. The lesion site appears to be critical for motor recovery. Lesions affecting the cerebellar nuclei are not fully compensated at any age and independent of the pathology in humans.

Adult↗

3D MTR measurement: from 1.5 T to 3.0 T.

This study investigates some of the issues involved in magnetization transfer ratio (MTR) acquisition, and in particular aims to determine whether high quality in vivo MTR measurements can be made at 3.0 T. The dependency of the MTR white-to-grey matter contrast to noise ratio (CNR) on MT pulse characteristics at 1.5 T and at 3.0 T was investigated using an established two-pool model for MT. The simulations showed that MT pulse parameters optimizing the CNR can be derived for both field strengths. Both the SNR and the CNR of MTR maps at 3.0 T were increased compared to 1.5 T. Images obtained using a safe in vivo MTR acquisition protocol based on results of simulations at 3.0 T are presented.

Artifacts↗

Gender difference analysis of cortical thickness in healthy young adults with surface-based methods.

We have examined gender differences of cortical thickness using a 3-D surface-based method that enables more accurate measurement in deep sulci and localized regional mapping compared to volumetric analyses. Cortical thickness was measured using a direct method for calculating the distance between corresponding vertices from inner and outer cortical surfaces. We normalized cortical surfaces using 2-D surface registration and performed diffusion smoothing to reduce the variability of folding patterns and to increase the power of the statistical analysis. In stereotaxic space, significant localized cortical thickening in women was found extensively in frontal, parietal and occipital lobes, including the superior frontal gyrus (SFG), superior parietal gyrus (SPG), inferior frontal gyrus (IFG) and postcentral gyrus (PoCG) in the left hemisphere and mostly in the parietal lobe, including the SPG in the right hemisphere. In the temporal lobe, small regions of the left and right caudal superior temporal gyrus (STG) and the left temporal pole showed significantly greater cortical thickness in women. The temporal lobe shows relatively less significant thickening than other lobes in both hemispheres. In native space, significantly greater cortical thickness in women was detected in left parietal region, including SPG and PoCG. No significant local increases of cortical thickness were observed in men in both spaces. These findings suggest statistically significant cortical thickening in women in localized anatomical regions, which is consistent with several previous studies and may support a hypothesis of sexual dimorphism.

Adolescent↗

Regional cortical thickness matters in recall after months more than minutes.

The aim of this study was to determine the role of regional cortical thickness in recall of verbal material over an extended time period. MRI scans of healthy adults of varying ages were obtained. Two scans were averaged per person to achieve high spatial resolution, and a semi-automated method for continuous measurement of thickness across the entire cortical mantle was employed. Verbal memory tests assessing recall after 5 min, 30 min, and a mean interval of 83 days were administered. A general linear model (GLM) of the effects of thickness at each vertex on the different memory indices was computed, controlling for gender, age, IQ, and intracranial volume. These analyses were repeated with hippocampal volume as an additional variable to be controlled for, to assess to which extent effects of cortical thickness were independent of hippocampal size. Minute effects of cortical thickness were observed with regard to shorter time intervals (5 and 30 min). However, even when controlling for the effects of hippocampal volume, higher recall across months was associated with thicker cortex of distinct areas including parts of the gyrus rectus, the middle frontal gyrus, the parieto-occipital sulcus and the lingual gyrus of both hemispheres. In addition, hemisphere-specific associations were found in parts of the right temporal and parietal lobe as well as parts of the left precuneus. This supports a unique and critical role of the thickness of distinct cortical areas in recall after months, more than after minutes.

Adult↗

Hierarchical microimaging for multiscale analysis of large vascular networks.

There is a wide range of diseases and normal physiological processes that are associated with alterations of the vascular system in organs. Ex vivo imaging of large vascular networks became feasible with recent developments in microcomputed tomography (microCT). Current methods permit to visualize only limited numbers of physically excised regions of interests (ROIs) from larger samples. We developed a method based on modified vascular corrosion casting (VCC), scanning electron microscopy (SEM), and desktop and synchrotron radiation microCT (SRmicroCT) technologies to image vasculature at increasing levels of resolution, also referred to as hierarchical imaging. This novel approach allows nondestructive 3D visualization and quantification of large microvascular networks, while retaining a precise anatomical context for ROIs scanned at very high resolution. Scans of entire mouse brain VCCs were performed at 16-microm resolution with a desktop microCT system. Custom-made navigation software with a ROI selection tool enabled the identification of anatomical brain structures and precise placement of multiple ROIs. These were then scanned at 1.4-microm voxel size using SRmicroCT and a local tomography setup. A framework was developed for fast sample positioning, precise selection of ROIs, and sequential high-throughput scanning of a large numbers of brain VCCs. Despite the use of local tomography, exceptional image quality was achieved with SRmicroCT. This method enables qualitative and quantitative assessment of vasculature at unprecedented resolution and volume with relatively high throughput, opening new possibilities to study vessel architecture and vascular alterations in models of disease.

Animals↗

Voxel-based morphometry in adolescents with bipolar disorder: first results.

Bipolar disorder is an increasingly recognized cause of significant morbidity in the pediatric age group. However, there is still a large degree of uncertainty regarding the underlying neurobiological deficits. In this preliminary study, we performed automated volumetric studies and whole-brain voxel-based morphometry (VBM) on gray matter. Imaging data from 10 adolescents with bipolar disorder were compared with data from 52 age- and gender-matched healthy controls. Previously defined brain parcellations and optimized VBM protocols were used, based on custom-made pediatric reference data. An additional, exploratory whole-brain comparison was also implemented. The volumetric region-of-interest study revealed significantly greater gray matter volume in central gray matter structures bilaterally (including the basal ganglia and the thalamus) and the left temporal lobe in the bipolar group. VBM confirmed bilaterally larger basal ganglia. Localized gray matter deficits in bipolar subjects were found in the medial temporal lobe, orbito-frontal cortex, and the anterior cingulate, confirming and extending earlier studies.

Adolescent↗

Assessment of the mean-value of 17-hydroxypregnenolone in the umbilical blood of newborns by the exploratory analysis of biochemical data.

The main aim of data analysis in biochemical metrology is the extraction of relevant information from biochemical data measurements. A system of extended exploratory data analysis (EDA) based on the concept of graphical tools for sample data summarization and exploration is proposed and the original EDA algorithm in S-Plus is available on the Internet at http://www.trilobyte.cz/EDA. To check basic assumptions about biochemical and medical data is to examine the independence of sample elements, sample normality and homogeneity. The exact assessment of the mean-value and the variance of steroid levels in controls is necessary for the correct assessment of the samples from patients. Data examination procedures are illustrated by a determination of the mean-value of 17-hydroxypregnenolone in the umbilical blood of newborns. For an asymmetric, strongly skewed sample distribution corrupted with outliers the best estimate of location seems to be the median. The Box-Cox transformation improves a sample symmetry. The proposed procedure gives reliable estimates of a mean-value for an asymmetric distribution of 17-hydroxypregnenolone when the arithmetic mean can not be used.

17-alpha-Hydroxypregnenolone↗

Distance measurements in nucleic acids using windowless dipolar recoupling solid state NMR.

A windowless, homonuclear dipolar recoupling pulse sequence (DRAWS) is described and a theoretical basis for describing its recoupling performance is developed using numerical techniques. It is demonstrated that DRAWS recouples weak dipolar interactions over a broad range of experimental and molecular conditions. We discuss two spectroscopic control experiments, which help to take into account effects due to insufficient proton decoupling, relaxation, and static dipolar couplings to nearby 13C spins at natural abundance. Finally DRAWS is used in combination with selective 13C labeling to measure 13C-13C distances in five doubly labeled DNA dodecamers, [d(CGCGAAT*T*CGCG)]2, which contain the binding site for the restriction enzyme EcoRI. The longest distance reported is 4.8 A. In most cases the distances agree well with those derived from X-ray crystallographic data, although small changes in hydration level can result in relatively large changes in internuclear distances.

Carbon Isotopes↗

Generalized least-squares method applied to fMRI time series with empirically determined correlation matrix.

Functional magnetic resonance imaging (fMRI) time series analysis and statistical inferences about the effect of a cognitive task on the regional cerebral blood flow (rCBF) are largely based on the linear model. However, this method requires that the error vector is a gaussian variable with an identity correlation matrix. When this assumption cannot be accepted, statistical inferences can be made using generalized least squares. In this case, knowledge of the covariance matrix of the error vector is needed. In the present report, we propose a method that needs stationarity of the autocorrelation function but is more flexible than autoregressive model of order p (AR(p)) models because it is not necessary to predefine a relation between coefficients of the correlation matrix. We tested this method on sets of simulated data (with presence of an effect of interest or not) representing a time series with a monotonically decreasing autocorrelation function. This time series mimicked an experiment using a random event-related design that does not create correlation between scans. The autocorrelation function is empirically determined and used to reconstitute the correlation matrix as the toeplitz matrix built from the autocorrelation function. When applied to simulated time series with no effect of interest, this method allows the determination of F values corresponding to the accurate false positive level. Moreover, when applied to time series with an effect of interest, this method gives a density function of F values which allows the rejection of the null hypothesis. This method provides a flexible but interpretable time domain noise model.

Attention↗

Comparing event-related and epoch analysis in blocked design fMRI.

In this study we demonstrate that, even in blocked design fMRI, an event-related analysis may provide a more accurate model of the hemodynamic responses than an epoch-related analysis. This is because the temporal shape of the predicted response differs between the event-related and the epoch model, with the former reaching its peak sooner and returning to baseline later than the latter. We present data from a blocked design fMRI study of single word reading alternated with rest. Conventionally, such a design would be analyzed using an epoch analysis with boxcar regressors. However, here we used a combined model in which trials were modeled as both single events and epochs. This allowed us to estimate the variance in the BOLD signal that was explained by either the event-related or the epoch regressors having discounted the effect of the other. We found that, in a number of language regions, the event-related model explained changes in activity that were not accounted for by the epoch model. In addition, we show that the advantage of the event-related over epoch model was engendered by its early onset rather than its late offset, relative to the epoch model.

Adult↗

Maintenance versus manipulation in verbal working memory revisited: an fMRI study.

Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.

Adult↗

EEG-correlated fMRI of human alpha activity.

Electroencephalography-correlated functional magnetic resonance imaging (EEG/fMRI) can be used to identify blood oxygen level-dependent (BOLD) signal changes associated with both physiological and pathological EEG events. Here, we implemented continuous and simultaneous EEG/fMRI to identify BOLD signal changes related to spontaneous power fluctuations in the alpha rhythm (8-12 Hz), the dominant EEG pattern during relaxed wakefulness. Thirty-two channels of EEG were recorded in 10 subjects during eyes-closed rest inside a 1.5-T magnet resonance (MR) scanner using an MR-compatible EEG recording system. Functional scanning by echoplanar imaging covered almost the entire cerebrum every 4 s. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. The average alpha power over 1-s epochs was derived at several electrode positions using a Fast Fourier Transform. The power time course was then convolved with a canonical hemodynamic response function, down-sampled, and used for statistical parametric mapping of associated signal changes in the image time series. At all electrode positions studied, a strong negative correlation of parietal and frontal cortical activity with alpha power was found. Conversely, only sparse and nonsystematic positive correlation was detected. The relevance of these findings is discussed in view of the current theories on the generation and significance of the alpha rhythm and the related functional neuroimaging findings.

Adult↗

Cerebellar volume and long-term use of phenytoin.

OBJECTIVES: To perform MRI cerebellum volumetry in patients exposed to phenytoin and to identify factors associated with cerebellar atrophy (CA). METHODS: From 100 consecutive epilepsy patients we selected those with phenytoin use for more than 2 months and with MRI scan available for volumetric studies. We obtained cerebellar volumes corrected for total intracranial volume. Volumes below 2 standard deviations from the mean of control group were considered abnormal. RESULTS: We studied 56 patients (33 women). Mean age was 33.6 years and mean duration of epilepsy was 17.6 years. Mean daily dose of phenytoin was 301 mg. CA was detected in 20 (35.7%) patients. CA was not associated with frequent generalised seizures. CA correlated with duration of epilepsy (r=-0.34; P=0.01) and years of treatment with phenytoin (r=-0.48; P=0.001), but not with age and mean daily dosage of phenytoin (P>0.05). However, a multiple correlation analysis as well as a backward stepwise multiple regression analysis including all variables showed that only duration of treatment was significantly associated with CA (P=0.001). CONCLUSIONS: CA is frequently associated with long-term use of phenytoin. Although duration of epilepsy may have an influence in the CA, this is clearly less important than the time of exposure to phenytoin.

Adolescent↗