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Biomedical subjects

P van Gelderen

Publications and source records attributed to P van Gelderen.

At least 19 recordsLinked to original sources

fMRI study of effort and information processing in a working memory task.

It is unclear how effort translates into brain function. In this study we endeavored to identify the activity in a working memory task that is related to the allocation of mental resources. Such activity, if present, would be a likely candidate to explain how effort works in terms of brain function. Eleven healthy participants performed a Sternberg task with a memory-set of one, three, or five consonants in an fMRI study. Probe stimuli were either one consonant or one digit. We expected digits to be processed automatically and consonants to require working memory. Because the probe type was unpredictable and subjects had to respond as fast as possible, we expected subjects to allocate mental resources on the basis of the memory-set size, not the probe type. Accordingly, we anticipated that activity in regions involved in effort would be a function of the size of the memory-set, but independent of the type of probe. We found that the reaction-time for digits increased in line with our expectation of automatic processing and the reaction time for letters increased in line with our expectation of controlled processing. fMRI revealed that activity in the right ventral-prefrontal cortex changed as a function of effort. The ventral anterior cingulate cortex and hypothalamus showed reduced activity as a function of effort. Activity in regions regarded as pivotal for working memory (among others, the left dorsolateral prefrontal cortex, anterior cingulate cortex) appeared to be predominantly related to information processing and not involved in effort.

Adult↗

CaB6: a new semiconducting material for spin electronics.

Ferromagnetism was recently observed at unexpectedly high temperatures in La-doped CaB6. The starting point of all theoretical proposals to explain this observation is a semimetallic electronic structure calculated for CaB6 within the local density approximation. Here we report the results of parameter-free quasiparticle calculations of the single-particle excitation spectrum which show that CaB6 is not a semimetal but a semiconductor with a band gap of 0.8+/-0.1 eV. Magnetism in La(x)Ca1-xB6 occurs just on the metallic side of a Mott transition in the La-induced impurity band.

Journal Article↗

High-sensitivity single-shot perfusion-weighted fMRI.

A method is presented for measurement of perfusion changes during brain activation using a single-shot pulsed spin labeling technique. By employing a double-inversion labeling strategy, stationary tissue (background) signal was suppressed while minimally affecting perfusion sensitivity. This allowed omission of the otherwise required reference scan, resulting in twofold-improved temporal resolution. The method was applied to visual and motor cortex activation studies in humans, and compared to standard FAIR-type perfusion labeling techniques. Experiments performed at 1.5T and 3.0T indicate a close to 90% suppression of background signal, at a cost of an 11% and 9%, respectively, reduction in perfusion signal. Combined with the twofold increase in signal averaging, and a reduction in background signal fluctuations, this resulted in a 64% (1.5T, N = 3) and a 128% (3T, N = 4) overall improvement in sensitivity for the detection of activation-related perfusion changes. Magn Reson Med 46:88-94, 2001. Published 2001 Wiley-Liss, Inc.

Brain↗

The role of the medial wall and its anatomical variations for bimanual antiphase and in-phase movements.

The medial wall of the frontal cortex is thought to play an important role for bimanual coordination. However, there is uncertainty regarding the exact neuroanatomical regions involved. We compared the activation patterns related to bimanual movements using functional magnetic resonance imaging in 12 healthy right-handed subjects, paying special attention to the anatomical variability of the frontal medial wall. The subjects performed unimanual right and left and bimanual antiphase and in-phase flexion and extension movements of the index finger. Activation of the right supplementary motor area (SMA) proper, right and left caudal cingulate motor area (CMA), and right and left premotor cortices was significantly stronger during bimanual antiphase than bimanual in-phase movements, indicating an important function of these areas with bimanual coordination. A frequent anatomical variation is the presence of the paracingulate sulcus (PCS), which might be an anatomical landmark to determine the location of activated areas. Seven subjects had a bilateral, three a unilateral right, and two a unilateral left PCS. Because the area around the PCS is functionally closer coupled to the CMA than to the SMA, activation found in the area around the PCS should be attributed to the CMA. With anatomical variations such as the presence of a PCS or a vertical branch of the cingulate sulcus, normalization and determination of the activation with the help of stereotaxic coordinates can cause an incorrect shift of CMA activation to the SMA. This might explain some of the discrepancies found in previous studies.

Adult↗

Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells.

Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

3T3 Cells↗

The variability of serial fMRI data: correlation between a visual and a motor task.

We investigated whether the intersession variability of serial fMRI studies correlates between two activation modalities, i.e. a standardized visual and a standardized motor task. Six volunteers were scanned in at least weekly intervals. The number of pixels activated as well as the activation amplitude varied widely. The maximal difference of the number of pixels activated was 1150%, of the activation amplitude 250%. In three volunteers, the variability was highly correlated between the two tasks. Three other volunteers showed one outlier each. We conclude that the intersession variability is due to global factors affecting the whole brain, but that due to unpredictable outliers, using a standardized task to normalize the data of interest is of limited value.

Adult↗

The relative metabolic demand of inhibition and excitation.

By using the (14C)2-deoxyglucose method, inhibition has been shown to be a metabolically active process at the level of the synapse. This is supported by recent results from magnetic resonance spectroscopy that related the changes in neuroenergetics occurring with functional activation to neurotransmitter cycling. However, inhibitory synapses are less numerous and strategically better located than excitatory synapses, indicating that inhibition may be more efficient, and therefore less energy-consuming, than excitation. Here we test this hypothesis using event-related functional magnetic resonance imaging in volunteers whose motor cortex was inhibited during the no-go condition of a go/no-go task, as demonstrated by transcranial magnetic stimulation. Unlike excitation, inhibition evoked no measurable change in the blood-oxygenation-level-dependent signal in the motor cortex, indicating that inhibition is less metabolically demanding. Therefore, the 'activation' seen in functional imaging studies probably results from excitation rather than inhibition.

Adult↗

Brain myo-inositol level is elevated in Ts65Dn mouse and reduced after lithium treatment.

The segmental trisomy Ts65Dn mouse is a novel model of Down syndrome (DS). The purpose of this study was to measure brain levels of myo-inositol (ml), N-acetylaspartate (NAA), and other metabolites in Ts65Dn mice using in vivo 1H magnetic resonance spectroscopy (MRS), and to determine whether lithium (Li) treatment alters brain ml level. The ratio of ml over total creatine (Cr), ml/Cr, was significantly elevated (mean change +38%), while NAA/Cr was significantly decreased (mean change -18%) in Ts65Dn mice (n=5) compared with control mice (n= 7). This is consistent with 1H MRS findings in DS human adults. Brain ml/Cr of the entire sample group (n= 12) was reduced (mean change -15%) following Li treatment, supporting the Li-induced ml depletion hypothesis.

Animals↗

Rapid three-dimensional MR imaging method for tracking a bolus of contrast agent through the brain.

A gradient-echo three-dimensional magnetic resonance imaging technique (principles of echo shifting with a train of observations, or PRESTO) is presented for use in tracking a bolus of paramagnetic contrast agent through the brain. The approach combines a segmented echo-planar type of acquisition with echo shifting, which leads to echo times that are longer than the repetition time. Unlike echo-planar imaging, the method maintains image resolution despite drastic T2* changes and frequency shifts.

Adult↗

Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination.

Demyelination is a common pathological finding in human neurological diseases and frequently persists as a result of failure of endogenous repair. Transplanted oligodendrocytes and their precursor cells can (re)myelinate axons, raising the possibility of therapeutic intervention. The migratory capacity of transplanted cells is of key importance in determining the extent of (re)myelination and can, at present, be evaluated only by using invasive and irreversible procedures. We have exploited the transferrin receptor as an efficient intracellular delivery device for magnetic nanoparticles, and transplanted tagged oligodendrocyte progenitor cells into the spinal cord of myelin-deficient rats. Cell migration could be easily detected by using three-dimensional magnetic resonance microscopy, with a close correlation between the areas of contrast enhancement and the achieved extent of myelination. The present results demonstrate that magnetic resonance tracking of transplanted oligodendrocyte progenitors is feasible; this technique has the potential to be easily extended to other neurotransplantation studies involving different precursor cell types.

Animals↗

Increased iron in the dentate nucleus of patients with Friedrich's ataxia.

Friedreich's ataxia (FA) is the most frequently inherited ataxia. To test the hypothesis that iron is increased in the cerebellum of patients with FA, we developed a multigradient echo magnetic resonance sequence for the three-dimensional imaging of brain iron-induced contrast. Relaxation rate (R2*) values in the unaffected globus pallidus were equal in FA patients and controls, although R2* values in the dentate nucleus of patients were significantly higher, which is most likely due to increased iron.

Adolescent↗

The effect of movement amplitude on activation in functional magnetic resonance imaging studies.

To evaluate the effect of movement amplitude on the "blood oxygen level-dependent effect," the authors studied six normal subjects while they extended their index finger with two different amplitudes. Images were analyzed using SPM96. In five subjects, the signal intensity increase in the primary sensorimotor area was significantly greater with the larger amplitude movement. In other areas of interest (supplementary motor area, premotor cortex, insula, postcentral area, cerebellum), the large-amplitude movement often showed significant activation when the small-amplitude movement did not. The authors conclude that, in studies of the motor system, movement amplitude needs to be controlled.

Adult↗

A comparison of fast MR scan techniques for cerebral activation studies at 1.5 tesla.

To evaluate the sensitivity of fast, gradient-echo MR scan techniques in their ability to detect blood oxygenation level dependent (BOLD) signal changes in task activation studies, three dedicated fast scan techniques, each with whole-brain coverage, were compared during a 3-min finger tapping paradigm on nine normal volunteers on a clinical 1.5 T scanner. Multislice (2D) single-shot spiral, 3D spiral, and multislice (2D) single-shot EPI scan techniques were done with similar temporal and spatial resolutions on each of the volunteers in random order. After image registration and statistical analysis, the sensitivity to detect activation was evaluated for the techniques by calculating t scores and number of activated voxels in predetermined regions of interest, including the contralateral primary sensorimotor cortex, the premotor region, the parietal region, the supplementary motor area, and the ipsilateral cerebellum. Baseline images acquired with the three techniques were qualitatively comparable and had a similar effective spatial resolution of around 5 x 5 x 5 mm3, as determined from autocorrelation analysis. The anatomical coverage was somewhat reduced (4 less slices per volume) with EPI at the identical temporal resolution of 1.76 s for all techniques. The use of multislice 2D spiral scan for motor cortex fMRI experiments provided for a superior overall temporal stability, and an increased sensitivity compared with multislice 2D EPI, and 3D spiral scan. The difference in sensitivity between multislice 2D spiral and EPI scans was small, in particular in the case of a ramp-sampled version of EPI. The difference in performance is attributed mainly to the difference in scan-to-scan stability.

Brain↗

Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia.

Functional magnetic resonance imaging (fMRI) is a potential paradigm shift in psychiatric neuroimaging. The technique provides individual, rather than group-averaged, functional neuroimaging data, but subtle methodological confounds represent unique challenges for psychiatric research. As an exemplar of the unique potential and problems of fMRI, we present a study of 10 inpatients with schizophrenia and 10 controls performing a novel "n back" working memory (WM) task. We emphasize two key design steps: (1) the use of an internal activation standard (i.e., a physiological control region) to address activation validity, and (2) the assessment of signal stability to control for "activation" artifacts arising from unequal signal variance across groups. In the initial analysis, all but one of the patients failed to activate dorsolateral prefrontal cortex (DLPFC) during the working memory task. However, some patients (and one control) also tended to show sparse control region activation in spite of normal motor performance, a result that raises doubts about the validity of the initial analysis and concerns about unequal subject motion. Subjects were then matched for signal variance (voxel stability), producing a subset of six patients and six controls. In this comparison, the internal activation standard (i.e., motor activation) was similar in both groups, and five of six patients, including two whom were neuroleptic-naive, failed to activate DLPFC. In addition, a tendency for overactivation of parietal cortex was seen. These results illustrate some of the promise and pitfalls of fMRI. Although fMRI generates individual brain maps, a specialized survey of the data is necessary to avoid spurious or unreliable findings, related to artifacts such as motion, which are likely to be frequent in psychiatric patients.

Adult↗

Single-shot diffusion MRI of human brain on a conventional clinical instrument.

A single-shot diffusion MRI technique on a standard clinical 1.5T scanner is presented. The method incorporates the following elements: (a) an inversion RF pulse followed by a delay of 1.3 s to null cerebral spinal fluid (CSF) signal, (b) a stimulated echo sequence (TE = 56 ms, TM = 100 ms) to obtain strong diffusion weighting, (c) a single-shot gradient- and spin-echo (GRASE) sequence for imaging with a modified k-space trajectory and Carr-Purcell Meiboom-Gill (CPMG)-phase cycle. The trace of the diffusion coefficient obtained with this approach is in good agreement with values reported for animal brain, and for recent human studies. It is demonstrated that single-shot diffusion imaging of human brain is feasible on an unmodified standard instrument without high-gradient slew rate or extreme field homogeneity.

Brain↗

Fast 3D functional magnetic resonance imaging at 1.5 T with spiral acquisition.

A new method to perform rapid 3D fMRI in human brain is introduced and evaluated in normal subjects, on a standard clinical scanner at 1.5 Tesla. The method combines a highly stable gradient echo technique with a spiral scan method, to detect brain activation related changes in blood oxygenation with high sensitivity. A motor activation paradigm with a duration of less than 5 min, performed on 10 subjects, consistently showed significant changes in signal intensity in the area of the motor cortex. In all subjects, these changes survived high statistical thresholds.

Brain↗

fMRI applications in schizophrenia research.

fMRI has unique potential in the study of psychiatric patients, particularly in characterizing individual variations and changes over time. We have performed four studies of patients with schizophrenia, using three different fMRI acquisition protocols: (1) 3-D echo-shifted FLASH, a multishot volumetric approach; (2) 3-D PRESTO, a hybid of multishot and echo-planar imaging (EPI) methods that also acquires true volumetric data; and (3) a whole-brain isotropic, multislice EPI technique. Patients were studied during sensorimotor activation and during a novel "N back" working memory paradigm. In general, patients show normal sensorimotor activation responses, although motor cortical activation tends to be less completely lateralized. Prefrontal activation during working memory tends to be reduced in patients with schizophrenia even when performance is normal. A major potential confound in studying this patient population with fMRI is the effect of motion. We propose several methodological standards to address this problem, including comparisons of motion corrections parameters, voxel variances, and the use of an "internal activation standard."

Adult↗