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PubMed1995

Functional MRI evidence for adult motor cortex plasticity during motor skill learning.

Performance of complex motor tasks, such as rapid sequences of finger movements, can be improved in terms of speed and accuracy over several weeks by daily practice sessions. This improvement does not generalize to a matched sequence of identical component movements, nor to the contralateral hand. Here we report a study of the neural changes underlying this learning using functional magnetic resonance imaging (MRI) of local blood oxygenation level-dependent (BOLD) signals evoked in primary motor cortex (M1). Before training, a comparable extent of M1 was activated by both sequences. However, two ordering effects were observed: repeating a sequence within a brief time window initially resulted in a smaller area of activation (habituation), but later in larger area of activation (enhancement), suggesting a switch in M1 processing mode within the first session (fast learning). By week 4 of training, concurrent with asymptotic performance, the extent of cortex activated by the practised sequence enlarged compared with the unpractised sequence, irrespective of order (slow learning). These changes persisted for several months. The results suggest a slowly evolving, long-term, experience-dependent reorganization of the adult M1, which may underlie the acquisition and retention of the motor skill.

Adult↗
PubMed1999

Comparison of evoked cortical activity in conscious and propofol-anesthetized rats using functional MRI.

Changes in cortical activity during foot shock were assessed under conscious and propofol-anesthetized conditions using functional magnetic resonance imaging (fMRI). Increases in signal intensity were observed in the contralateral somatosensory cortex in response to electrical shock of the hindpaw under both conditions. These increases in cortical signal ranged from 6% to 26% while awake and from 1% to 6% under propofol anesthesia. In each of the six animals studied, the largest increase in blood oxygenation level-dependent (BOLD)-based signal intensity was observed during consciousness. In three of six animals, propofol anesthesia depressed signal intensity by as much as 10-fold, showing that the level of cortical activity during foot shock is dampened by anesthesia. These results indicate it would be advantageous to use fully conscious animals to maximize BOLD-based MRI signal in certain behavioral studies using MR spectrometers with modest field strengths (1.0-2.0 T).

Anesthesia, General↗
PubMed1998

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

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

Adult↗
PubMed2003

Wavelet statistics of functional MRI data and the general linear model.

PURPOSE: To improve the signal-to-noise ratio (SNR) of functional magnetic resonance imaging (fMRI) data, an approach is developed that combines wavelet-based methods with the general linear model. MATERIALS AND METHODS: Ruttimann et al. (1) developed a wavelet-based statistical procedure to test wavelet-space partitions for significant wavelet coefficients. Their method is applicable for the detection of differences between images acquired under two experimental conditions using long blocks of stimulation. However, many neuropsychological questions require more complicated event-related paradigms and more experimental conditions. Therefore, in order to apply wavelet-based methods to a wide range of experiments, we present a new approach that is based on the general linear model and wavelet thresholding. RESULTS: In contrast to a monoresolution filter, the application of the wavelet method increased the SNR and showed a set of clearly dissociable activations. Furthermore, no relevant decrease of the local maxima was observed. CONCLUSION: Wavelet-based methods can increase the SNR without diminishing the signal amplitude, while preserving the spatial resolution of the image. The anatomical localization is strongly improved.

Adult↗
PubMed1998

Functional MRI of somatosensory activation in rat: effect of hypercapnic up-regulation on perfusion- and BOLD-imaging.

Functional activation of somatosensory cortex was studied in alpha-chloralose anesthetized rats by functional magnetic resonance imaging (fMRI), using both perfusion-weighted and T2*-weighted (blood oxygenation level dependent, BOLD) imaging. The sensitivity of functional activation was altered by ventilating animals for 3 minutes with 6% CO2. Before hypercapnic conditioning, electrical stimulation of the left forepaw at a frequency of 3 Hz led to an increase of signal intensity (relative to the unstimulated baseline condition) in the right somatosensory cortex by 6+/-2% (means+/-SD) in T2*-weighted images and by 45%+/-48% in perfusion-weighted images. After hypercapnic conditioning the signal intensity increase in perfusion-weighted images doubled to 91%+/-62% (P=0.034), whereas that of T2*-weighted images only marginally increased to 7+/-4% (not significant). This different behavior in both imaging modalities is interpreted as evidence for an increased flow response in combination with a higher oxygen extraction. Thus, the fMRI data reflect hypercapnia-induced resetting of the functional-metabolic coupling of the tissue during activation.

Animals↗
PubMed2000

Application of cortical unfolding techniques to functional MRI of the human hippocampal region.

We describe a new application of cortical unfolding to high-resolution functional magnetic resonance imaging (fMRI) of the human hippocampal region. This procedure includes techniques to segment and unfold the hippocampus, allowing the fusiform, parahippocampal, perirhinal, entorhinal, subicular, and CA fields to be viewed and compared across subjects. Transformation parameters derived from unfolding high-resolution structural images are applied to coplanar, functional images, yielding two-dimensional "unfolded" activation maps of hippocampi. The application of these unfolding techniques greatly enhances the ability of fMRI to localize and characterize signal changes within the medial temporal lobe. Use of this method on a novelty-encoding paradigm reveals a temporal dissociation between activation along the collateral sulcus and activation in the hippocampus proper.

Adult↗
PubMed2003

Relation between regional functional MRI activation and vascular reactivity to carbon dioxide during normal aging.

Recent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging studies have shown a reduction of cerebral activation during aging, which may be associated with age-related changes of the cerebral vascular system. The authors used a global hypercapnic breath-holding challenge to define nonneuronal contributions to a significantly reduced activation in the primary sensorimotor cortex during finger tapping in a group of old (n = 6; mean age 65 years) compared with a group of young (n = 6; mean age 27 years) subjects. Within significantly activated voxels in both groups during finger tapping, the mean BOLD signal amplitudes were significantly smaller in the group of older subjects for both tasks. In those voxels showing significant activation only in young subjects during finger tapping, the response to hypercapnia was also greatly diminished in older subjects. The attenuated hypercapnic BOLD signal response in older subjects within this region suggests that age-dependent changes of the cerebral vasculature may alter the neuronal-vascular coupling. In older subjects, cerebral vessels may not react as effectively in response to a vasodilating stimulus, which will lead to differences in the number of voxels that pass a criterion threshold despite similar neuronal activation.

Adult↗
PubMed2004

Regional intensive and temporal patterns of functional MRI activation distinguishing noxious and innocuous contact heat.

Cortical responses to painful and nonpainful heat were measured using functional magnetic resonance imaging (fMRI) region of interest analysis (ROI) of primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate (ACC), supplementary motor area (SMA), insula, and inferior frontal gyrus (IFG). Previous studies indicated that innocuous and noxious stimuli of different modalities produce responses with different time courses in S1 and S2. The aim of this study was to 1) determine whether temporally distinct nociceptive blood oxygen level-dependent (BOLD) responses are evoked in multiple somatosensory processing cortical areas and 2) whether these responses discriminate small noxious stimulus intensity differences. Thirty-three subjects underwent fMRI scanning while receiving three intensities of thermal stimuli, ranging from innocuous warm (41 degrees C) to 1 degrees C below tolerance, applied to the dorsum of the left foot. Innocuous and noxious responses were distinguishable in contralateral S1, the mid-ACC, and SMA. The peak of the nociceptive response was temporally delayed from the innocuous response peak by 6-8 s. Responses to noxious but not to innocuous stimuli were observed in contralateral posterior insula. Responses to innocuous and noxious stimuli were not statistically different in contralateral S2. In contralateral S1 only, the nociceptive response could differentiate heat stimuli separated by 1 degrees C. These results show that 1) multiple cortical areas have temporally distinguishable innocuous and noxious responses evoked by a painfully hot thermode, 2) the nociceptive processing properties vary across cortical regions, and 3) nociceptive responses in S1 discriminate between painful temperatures at a level unmatched in other cortical areas.

Adult↗
PubMed2006

Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study.

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 +/- 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.

Adolescent↗
PubMed2002

[Morphological and functional MRI studies after correction of aortic isthmus stenosis].

PURPOSE: To compare the results of different methods for postoperative assessment after coarctation repair by magnetic resonance imaging and to evaluate their reliability. The morphometric results are contrasted to functional parameters of CW Doppler, oscillometric pressure gradient and flow quantification in VEC-MRI. METHODS: 54 patients (age: 6 to 36 years) were assessed by MRI 3 to 31 years after coarctation repair. The aortic diameters were compared to growth-dependent normal values and to the diameter of the ascending (AA) and descending aorta (DA), and their mean values (MV). RESULTS: Patients after coarctation repair had mostly subnormal diameters of AA (mean value: 80% of normal) and AD (95% of normal). Compared to the control group, mean dispersion of AD diameters was significantly larger in the patient group (2.6 vs. 1.5 mm, p < 0.001). Degree of stenosis varied with the method. It was similar when using normal values and the diameter for DA, but dispersion was smaller when normal values were used. Correlation of the functional parameter to the degree of stenosis was weak. The highest correlation (r = 0.78) was reached when using normal values as the reference with mean cross-sectional velocity from VEC-MRI. CONCLUSION: The use of normal values as the reference for quantification of residual coarctation is more reliable than common methods. Since only one measurement is needed, it seems to be less susceptible to errors and more practical. MRI offers not only a tool for accurate morphologic assessment, but with VEC-MRI it is also possible to obtain a functional parameter which is superior to oscillometric pressure gradient and CW Doppler.

Adolescent↗
PubMed2004

Functional MRI of the rodent somatosensory pathway using multislice echo planar imaging.

A multislice EPI sequence was used to obtain functional MR images of the entire rat brain with BOLD contrast at 11.7 T. Ten to 11 slices covering the rat brain, with an in-plane resolution of 300 microm, provided enough sensitivity to detect activation in brain regions known to be involved in the somatosensory pathway during stimulation of the forelimbs. These regions were identified by warping a digitized rat brain atlas to each set of images. Data analysis was constrained to four major areas of the somatosensory pathway: primary and secondary somatosensory cortices, thalamus, and cerebellum. Incidence maps were generated. Electrical stimulation at 3 Hz led to significant activation in the primary sensory cortex in all rats. Activation in the secondary sensory cortex and cerebellum was observed in 70% of the studies, while thalamic activation was observed in 40%. The amplitude of activation was measured for each area, and average response time courses were calculated. Finally, the frequency dependence of the response to forepaw stimulation was measured in each of the activated areas. Optimal activation occurred in all areas at 3 Hz. These results demonstrate that whole-brain fMRI can be performed on rodents at 11.7 T to probe a well-defined neural network.

Animals↗
PubMed1999

High-resolution mapping of discrete representational areas in rat somatosensory cortex using blood volume-dependent functional MRI.

The present study documents the use of an iron oxide-based blood-pool contrast agent in functional magnetic resonance imaging to monitor activity-related changes in cerebral blood volume (CBV) resulting from peripheral sensory stimulation and the application of this technique to generate high-resolution functional maps. Rats, anesthetized with alpha-chloralose, were imaged during electrical stimulation (3 ms, 3 Hz, 3 V) of forelimb or hindlimb. Activation maps were generated by cross-correlation of the measured signal response and a square-wave function representative of the stimulus for each image pixel. Multislice imaging produced functional maps consistent with the known functional anatomy of rat primary somatosensory (S-I) cortex. Imaging with improved temporal resolution demonstrated rapid (<6 s) CBV increases which were sustained and relatively stable (coefficient of variation = 0.17 +/- 0.02) for forelimb stimulation periods of up to 5 min. Enabled by this sustained response we generated high-resolution (approximately 100 micrometer in-plane) functional maps showing discrete forelimb and hindlimb activation. This technique offers many advantages over other methods for the study of brain activity in the rat and has resolution sufficient to be useful in reorganization studies.

Animals↗
PubMed2006

The assessment of hemispheric lateralization in functional MRI--robustness and reproducibility.

Various methods have been proposed to calculate a lateralization index (LI) on the basis of functional magnetic resonance imaging (fMRI) data. Most of them are either based on the extent of the activated brain region (i.e., the number of "active" voxels) or the magnitude of the fMRI signal change. The purpose of the present study was to investigate the characteristics of various variants of these approaches and to identify the one that yields the most robust and reproducible results. Robustness was assessed by evaluating the dependence on arbitrary external parameters, reproducibility was assessed by Pearson's correlation coefficient. LIs based on active voxels counts at one single fixed statistical threshold as well as LIs based on unthresholded signal intensity changes (i.e., based on all voxels in a region of interest) yielded neither robust nor reproducible laterality results. Instead, the lateralization of a cognitive function was best described by "thresholded" signal intensity changes where the activity measure was based on signal intensity changes in those voxels in a region of interest that exceeded a predefined activation level. However, not all other approaches should be discarded completely since they have their own specific application fields. First, LIs based on active voxel counts in the form of p-value-dependent lateralization plots (LI=LI(p)) can be used as a straightforward measure to describe hemispheric dominance. Second, LIs based on active voxel counts at variable thresholds (standardized by the total number of active voxels) are a good alternative for big regions of interest since LIs based on signal intensity changes are restricted to small ROIs.

Adult↗
PubMed2005

A functional MRI comparison of patients with obsessive-compulsive disorder and normal controls during a Chinese character Stroop task.

Recent functional neuroimaging and neuropsychological studies have suggested that abnormal activity in the anterior cingulate cortex (ACC) might cause an action-monitoring dysfunction in obsessive-compulsive disorder (OCD). To identify the relationship between brain dysfunction and cognitive dysfunction, we examined regional brain changes in OCD with functional magnetic resonance imaging (fMRI) during the performance of a cognitive task. Participants comprised 24 patients with OCD and 14 normal controls. First, we compared the cognitive function in the two groups as assessed by several neuropsychological tests. Then we used fMRI to explore brain correlates of their performance during the Chinese character version of the Stroop test, a task that is strongly related to action-monitoring function. The two groups did not differ on the neuropsychological tests. Both groups also showed similar activation pattern on fMRI. The patients, however, showed weaker activation than the normal controls in the ACC and the right caudate nucleus.

Adult↗
PubMed1998

High-field (3.0 T) functional MRI sequential epoch analysis: an example for motion control analysis.

The widely accepted method of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is a subtractive approach of state related analysis based on pictorial statistics, analogous to its predecessor, H2O(15) positron emission tomography (H2O(15)-PET). Although BOLD-fMRI has been shown to have several definite advantages over H2O(15)-PET, it has also been found to be much more artifact prone. This is primarily due to pixel misalignment of raw image data. Furthermore, similar to H2O(15)-PET, conventional means for pictorial analysis in BOLD-fMRI tends to be limited by the relatively low specificity of the observed activation. To overcome this limitation, we investigated a technique for BOLD-fMRI, sequential epoch analysis (SEA), on a high-field (3.0 T) system. The method allows for experimental designs comparable to neurophysiological techniques in primates and enables determination of activation of a selected cerebral cortical region of interest corresponding to a specific task. Utilizing SEA, we successfully identified a specific area within the premotor cortex which is activated complementary to the contralateral hand motion. The findings have strong implications regarding the neurological substrate responsible for the well described clinical phenomenon of physiological mirror movements in infants. The current study validated SEA BOLD-fMRI on a high-field system as a complementary method in the pictorial analysis of conventional fMRI, effectively offsetting the inherent problems of the conventional method, principally pixel misalignment and the relatively low specificity of the observed activation.

Adolescent↗
PubMed1999

The effects of k-space data undersampling and discontinuities in keyhole functional MRI.

The effects of the k-space data undersampling and the discontinuities associated with the keyhole approach in functional magnetic resonance imaging (fMRI) have been addressed. Undersampling of high k-space data increases the high spatial-frequency noise by a factor of square root m, where m is the number of images sharing the high k-space data. However, the effects of the noise can be effectively removed using clustered-pixel statistical analysis. The amplitude and phase discontinuities may result in an increase in the low spatial-frequency noise level, which has no impact on specificity and only a minimal impact on sensitivity. Although dramatically reducing acquisition time and preserving the spatial resolution of functional magnetic resonance imaging, the keyhole technique may have a limited capability in detecting highly focal activations.

Algorithms↗
PubMed1997

Somatotopy in the human motor cortex hand area. A high-resolution functional MRI study.

Fine-scale somatotopic encoding in brain areas devoted to sensorimotor processing has recently been questioned by functional neuroimaging studies which suggested its absence within the hand area of the human primary motor cortex. We re-examined this issue by addressing somatotopy both in terms of functional segregation and of cortical response preference using oxygenation-sensitive magnetic resonance imaging at high spatial resolution. In a first step, spatial representations of self-paced isolated finger movements were mapped by using motor rest as a control state. A subsequent experimental design studied the predominance of individual finger movements by using contrasting finger movements as the control task. While the first approach confirmed previous reports of extensive overlap in spatial representations, the second approach revealed foci of differential activation which displayed an orderly mediolateral progression in accordance with the classical cortical motor homunculus. We conclude that somatotopy within the hand area of the primary motor cortex does not present as qualitative functional segregation but as quantitative predominance of certain movement or digit representation embedded in an overall joint hand area.

Adult↗