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Non-invasive regime for language lateralization in right- and left-handers by means of functional MRI and dichotic listening.

Language lateralization was assessed by two independent functional techniques, fMRI and a dichotic listening test (DLT), in an attempt to establish a reliable and non-invasive protocol of dominance determination. This should particularly address the high intraindividual variability of language lateralization and allow decision-making in individual cases. Functional MRI of word classification tasks showed robust language lateralization in 17 right-handers and 17 left-handers in terms of activation in the inferior frontal gyrus. The DLT was introduced as a complementary tool to MR mapping for language dominance assessment, providing information on perceptual language processing located in superior temporal cortices. The overall agreement of lateralization assessment between the two techniques was 97.1%. Conflicting results were found in one subject, and diverging indices in ten further subjects. Increasing age, non-familial sinistrality, and a non-dominant writing hand were identified as the main factors explaining the observed mismatch between the two techniques. This finding stresses the concept of an intrahemispheric distribution of language function that is obviously associated with certain behavioral characteristics.

Adult↗

Effect of acute hyperglycemia on visual cortical activation as measured by functional MRI.

To determine whether acute hyperglycemia changes the hyperemic response to functional activation of brain, the area and magnitude of the activation were measured in healthy volunteers maintained at euglycemia and then at hyperglycemia using the hyperglycemic clamp technique. Activation of the visual cortex (8-16 Hz) was assessed by functional MRI with blood oxygenation level dependent (BOLD) contrast using a 4 Tesla magnet and a multi-slice echo-planar imaging sequence (TE = 30 msec, TR = 1.5 sec). At euglycemia (4.8 +/- 0.2 mM, mean +/- SEM, n = 6), the number of activated pixels in the occipital lobe was 79 +/- 10 and the intensity of activation was 4.5 +/- 0.5%. During hyperglycemia (plasma glucose 300% of control), the number of activated pixels was 90 +/- 20% of control and the BOLD activation was 3.5 +/- 0.3%, respectively. The change in BOLD signal was below 0.2%/mM plasma glucose. This study demonstrates that acute hyperglycemia is without substantial effect on the size and intensity of activation of the occipital cortex. The results further suggest that fluctuations in blood glucose within the physiologic range are without effect on the functional activation of the cerebral cortex measured by BOLD fMRI.

Adult↗

Eye dominance in the visual cortex using functional MRI at 1.5 T: an alternative method.

PURPOSE: To develop a functional MRI method for producing eye dominance histograms in humans at 1.5 Tesla (T). METHODS: In the first set of experiments, 8 normal persons were tested. The eye dominance of each voxel within the person's visually activated primary visual cortex was determined with Student t statistics during a left eye versus right eye contrast. Eye dominance distribution was plotted, and the mean t statistic was used to describe the histogram asymmetry. In the second set of experiments, the effect of monocular optical blur and decreased luminance via filter was studied, and eye dominance distributions were similarly determined. RESULTS: The eye dominance histogram in each of the 8 normals was approximately symmetric; the average mean t value was +0.13. All 4 subjects with the right eye blurred had histograms approximately symmetric or slightly shifted toward the left eye (average mean t = +0.56), and all 4 subjects with the right eye filtered had histograms dramatically shifted toward the left eye (average mean t = +2.22). The average mean t for the group with the right eye filtered was significantly different from that of the other 2 groups (P <.0001). CONCLUSIONS: With noninvasive methods in normal persons, functional magnetic resonance imaging techniques at 1.5 T were able to characterize the distribution of eye dominance of voxels in primary visual cortex, based upon their t statistic in the left eye versus right eye contrast. The method is sensitive to filtering but relatively insensitive to visual blur. This approach may have a future use in the study of amblyopia in humans.

Adolescent↗

Recovery of semantic word processing in global aphasia: a functional MRI study.

One important issue concerning the recovery of higher cognitive functions-such as word comprehension in aphasia-is to what extent impairments can be compensated for by intact parts of the network of areas normally involved in a closely related function ("redundancy recovery"). In a previous functional MRI investigation, we were able to show that left hemispheric redundancy recovery within a distributed system of related lexical-semantic functions was the most probable basis of recovery of comprehension from transcortical sensory aphasia. The question remained, however, whether redundancy recovery may play a more general role in the recovery of comprehension after large left hemispheric lesions and severe aphasia. We had the possibility, using the same fMRI paradigm, to study seven cases with left middle cerebral artery (MCA) infarction and partial recovery of comprehension > or =6 months after presentation with global aphasia on acute assessment. Lateralization of activation did not differ significantly between patients and controls. The most consistent regions of activation included the left extrasylvian posterior temporal and the right posterior parietal cortex. Recovery of language comprehension was associated predominantly with activations in regions, which were also activated in several normal subjects. We suggest that a redundancy recovery mechanism within multiple representations of closely related functions was more important than take-over of function by previously unrelated areas (vicariation) as the basis of recovery of word comprehension in our patients in spite of extensive left hemispheric damage. We conclude that redundancy within the lexical-semantic system seems to make an important contribution to recovery of comprehension even in severe aphasia.

Acoustic Stimulation↗

Brain activation during the fist-edge-palm test: a functional MRI study.

The purpose of our study is to clarify, using functional MRI, brain regions activated during the fist-edge-palm task (FEP) compared to relatively simple hand motor tasks using either the right or the left hand in right-handed normal volunteers. The FEP was introduced to detect a disorder of voluntary movement, and it is believed to be closely related to contralateral frontal lobe damage. However, this assumption still remains controversial. Ten subjects participated in this study. Hand motor tasks were as follows: (1) the FEP, in which the subjects were requested to place their hand in three different positions sequentially: a fist resting horizontally, a palm resting vertically, and a palm resting horizontally; (2) a fist-palm task (FP), in which the subjects were asked to clench and unclench their fist alternately; and (3) a control task requiring the subjects to knock lightly with their clenched fist. The contralateral sensomotor and premotor areas were activated in the FP with the right hand and the contralateral sensorimotor, premotor, and supplementary motor areas (SMA) were activated in the FP with the left hand. In the FEP with either hand, bilateral premotor and left parietal areas and ipsilateral cerebellum were also activated as well as contralateral sensorimotor area and SMA. Our results suggest that successful performance of the FEP requires the participation of more brain areas than FP, which may explain why some patients without frontal lobe damage failed to perform the FEP.

Adult↗

Functional MRI using steady-state arterial water labeling.

Flow-sensitive functional MRI (fMRI) was performed using steady-state arterial water labeling (SS-AWL). Arterial water labeling was accomplished by flow induced adiabatic fast passage. The signal intensity of the visual cortex in arterial water labeled images decreased by approximately 1.4% during visual stimulation of the brain. Acquisition of arterial water unlabeled and labeled images allows measurement of relative cerebral blood flow increase during brain activation. During visual stimulation, cerebral blood flow in the visual cortex increased by 17 to 35% as measured by SS-AWL. Quantitation of brain activation in terms of a physiological parameter using SS-AWL will facilitate comparative fMRI studies under different conditions.

Adult↗

Hemodynamic and electroencephalographic responses to illusory figures: recording of the evoked potentials during functional MRI.

The feasibility of recording event-related potentials (ERP) during functional MRI (fMRI) scanning using higher level cognitive stimuli was studied. Using responses to illusory figures in a visual oddball task, evoked potentials were obtained with their expected configurations and latencies. A rapid stimulation scheme using randomly varied trial lengths was employed, and class-wise characteristics of the hemodynamic response were obtained by a nonlinear analysis of the fMRI time series. Implications and limitations of conducting combined ERP-fMRI experiments using higher level cognitive stimuli are discussed. EEG/fMRI results revealed a sequential activation of striate and extrastriate occipital cortex along the ventral path of object processing for Kanizsa figures. Interestingly, Kanizsa figures activated the human motion area MT. Targets resulted in activations of frontal and parietal cortex which were not activated for standard stimuli.

Adult↗

Functional MRI of galvanic vestibular stimulation with alternating currents at different frequencies.

Functional MRI was performed in 28 healthy volunteers to study the effects of galvanic vestibular stimulation with alternating currents (AC-GVS) of different frequencies on brain activation patterns. The aims of this study were (1) to identify specific areas within the vestibular cortical network that are involved in the processing of frequency-specific aspects by correlation analyses, (2) to determine the optimal frequency for stimulation of the vestibular system with respect to perception, and (3) to analyze whether different frequencies of AC-GVS are mediated in different cortical areas or different sites within the vestibular cortex. AC-GVS was performed using sinusoidal stimulation currents with an amplitude of +/-2.5 mA, and frequencies of 0.1 Hz, 0.3 Hz, 0.8 Hz, 1.0 Hz, 2.0 Hz, and 5.0 Hz were applied. Regardless of the applied stimulation frequency, AC-GVS elicited activations within a network of multisensory areas similar to those described in earlier studies using direct currents. No mapping of different stimulation frequencies to different cortical locations was observed. Additional activations of somatosensory cortex areas were observed during stimulation with 5 Hz only. The strongest vestibular sensations were reported during stimulation with 1 Hz and 2 Hz. Correlation analyses between blood oxygenation level dependent (BOLD) signal changes and stimulation frequency revealed a positive dependency in areas of the supramarginal gyrus, posterolateral thalamus, cerebellar vermis, posterior insula, and in the hippocampal region/uncus. These regions represent areas involved in the processing of vestibular information for head and body orientation in space.

Adult↗

"Willed action": a functional MRI study of the human prefrontal cortex during a sensorimotor task.

Functional MRI (fMRI) was used to examine human brain activity within the dorsolateral prefrontal cortex during a sensorimotor task that had been proposed to require selection between several responses, a cognitive concept termed "willed action" in a positron emission tomography (PET) study by Frith et al. [Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991) Proc. R. Soc. London Ser. B 244, 241-246]. We repeated their sensorimotor task, in which the subject chooses to move either of two fingers after a stimulus, by fMRI experiments in a 2.1-T imaging spectrometer. Echo-planar images were acquired from four coronal slices in the prefrontal cortex from nine healthy subjects. Slices were 5 mm thick, centers separated by 7 mm, with nominal in-plane spatial resolution of 9.6 x 5.0 mm2 for mean data. Our mean results are in agreement with the PET results in that we saw similar bilateral activations. The present results are compared with our previously published fMRI study of a verbal fluency task, which had also been proposed by Frith et al. to elicit a "willed action" response. We find a clear separation of activation foci in the left dorsolateral prefrontal cortex for the sensorimotor (Brodmann area 46) and verbal fluency (Brodmann area 45) tasks. Hence, assigning a particular activated region to "willed action" is not supported by the fMRI data when examined closely because identical regions are not activated with different modalities. Similar modality linked activations can be observed in the original PET study but the greater resolution of the fMRI data makes the modality linkages more definite.

Female↗

Creating connected representations of cortical gray matter for functional MRI visualization.

We describe a system that is being used to segment gray matter from magnetic resonance imaging (MRI) and to create connected cortical representations for functional MRI visualization (fMRI). The method exploits knowledge of the anatomy of the cortex and incorporates structural constraints into the segmentation. First, the white matter and cerebral spinal fluid (CSF) regions in the MR volume are segmented using a novel techniques of posterior anisotropic diffusion. Then, the user selects the cortical white matter component of interest, and its structure is verified by checking for cavities and handles. After this, a connected representation of the gray matter is created by a constrained growing-out from the white matter boundary. Because the connectivity is computed, the segmentation can be used as input to several methods of visualizing the spatial pattern of cortical activity within gray matter. In our case, the connected representation of gray matter is used to create a flattened representation of the cortex. Then, fMRI measurements are overlaid on the flattened representation, yielding a representation of the volumetric data within a single image. The software is freely available to the research community.

Cerebral Cortex↗

Myths and truths in functional MRI: a basic guide for practitioners.

Since the first successful demonstration of primary visual cortex "activation" by Sokoloff in 1961, activation studies based on regional blood flow alteration became one of the gold standards for neuroscientific investigation. The rapid advancement of non-invasive imaging techniques provided an appropriate stage for the human application of this original method. Following the tremendous success of positron emission tomography (PET) utilizing O(15) labeled H(2)O (H(2)O(15)-PET), the magnetic resonance imaging (MRI) version, which is now referred to as functional MRI (fMRI), was introduced. fMRI is the method created based on the empirical observation that MRI exhibits spontaneous signal alteration associated with blood flow changes. It is now believed that the principle of fMRI is identical to H(2)O(15)-PET, namely, that it is blood flow based in accordance with the well-known Munro-Kellie doctrine which predicts a decline in cerebral venous blood volume secondary to an increase in cerebral arterial blood volume. The method is inherently qualitative and does not provide quantitative information regarding flow alteration. With the growing use of fMRI, however, exponentially increasing well founded criticism questioning the validity of fMRI data has been raised. The majority of validation issues arise during the process of obtaining raw images, which eventually provides raw numerical data for post-processing statistical analysis. This article provides a distillation of the essential knowledge necessary for the non-MR physicist fMRI investigator.

Brain Mapping↗

Fuzzy clustering of gradient-echo functional MRI in the human visual cortex. Part I: reproducibility.

Reproducibility of human functional MRI (fMRI) studies is essential for clinical and neuroresearch applications of this new human brain mapping method. Based on a recently presented study on reproducibility of gradient-echo fMRI in the human visual cortex (Moser et al. Magn Reson Imaging 1996; 14:567-579), comparing the performance of three different threshold strategies for correlation analysis, we demonstrate that (a) fuzzy clustering is a robust, model-independent method to extract functional information in time and space; (b) intertrial reproducibility of cortical activation is significantly improved by the capability of fuzzy clustering to separate signal contributions from larger vessels, running perpendicular to the slice orientation, from activation apparently close to the primary visual cortex; and (c) for repeated single subject studies, SDs of <20% for signal enhancement in approximately 80% of the studies and SDs of <30% for activated area size in approximately 65% of the studies are obtained. This, however, depends also on signal-to-noise ratio, (motion) artifacts, and subject cooperation.

Adult↗

Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical power analyses.

Estimation of statistical power in functional MRI (fMRI) requires knowledge of the expected percent signal change between two conditions as well as estimates of the variability in percent signal change. Variability can be divided into intra-subject variability, reflecting noise within the time series, and inter-subject variability, reflecting subject-to-subject differences in activation. The purpose of this study was to obtain estimates of percent signal change and the two sources of variability from fMRI data, and then use these parameter estimates in simulation experiments in order to generate power curves. Of interest from these simulations were conclusions concerning how many subjects are needed and how many time points within a scan are optimal in an fMRI study of cognitive function. Intra-subject variability was estimated from resting conditions, and inter-subject variability and percent signal change were estimated from verbal working memory data. Simulations derived from these parameters illustrate how percent signal change, intra- and inter-subject variability, and number of time points affect power. An empirical test experiment, using fMRI data acquired during somatosensory stimulation, showed good correspondence between the simulation-based power predictions and the power observed within somatosensory regions of interest. Our analyses suggested that for a liberal threshold of 0.05, about 12 subjects were required to achieve 80% power at the single voxel level for typical activations. At more realistic thresholds, that approach those used after correcting for multiple comparisons, the number of subjects doubled to maintain this level of power.

Adult↗

[Functional MRI of the pelvic floor. The methods and reference values].

PURPOSE: Functional cine MRI of the pelvic floor is a yet another modality in addition to various radiological fluoroscopic techniques. This article describes our own method in view of the recent literature and provides morphometric reference values. MATERIAL AND METHOD: We examined 20 nulliparous women (range of age: 25-51 years) with normal findings in the gynecological and urodynamic examination. Functional cine MRI was performed on a 1.5 Tesla equipment after opacification of the vagina and rectum. We used a T2-weighted gradient-echo sequence (Ture-FISP) to determine the position of the reference organs at rest and during straining/defecation. Two different reference lines were used. In addition 29 morphometric and functional parameters were measured, all of them being observer independent. RESULTS: Functional cine MRI was able to show the extent and interaction of the pelvic floor organs in all cases with the reference organs always remaining above the pubococcygeal reference line. The depth of the rectocele was 2 cm. With the exception of the diameter of urogenital hiatus the different parts of the levator ani muscle could not be determined. DISCUSSION: Functional cine MRI using an appropriate organ opacification and slice positioning is an objective, unifying diagnostic approach of the pelvic floor. The reference data given can be of help to distinguish normal from abnormal findings.

Adult↗

Functional MRI today.

Most brain imaging researchers would agree with the assertion that functional MRI (fMRI) is progressing. Since fMRI began in 1991, the number of people, papers, and abstracts related to fMRI has been increasing; the technology and methodology has shown advances in robustness and sophistication; the physiology of the signal is better understood; and, even though it hasn't yet made significant headway into the clinical setting, applications are widening. Questions that stem from this optimistic and perhaps overly general set of observations include those that ask what the ultimate theoretical and practical limits of fMRI are and how close are we to approaching these limits. In this commentary, I attempt to provide a snapshot of fMRI as it exists at the end of 2005, and to give a clear impression that not only are we progressing by "dotting the i's and crossing the t's" but that fundamental changes in fMRI methodology and processing are being put forth as the field matures.

Bibliometrics↗

Quantitative assessment of skeletal muscle activation using muscle functional MRI.

The purpose of the present study is to determine whether muscle functional MRI (mfMRI) can be used to obtain three-dimensional (3-D) images useful for evaluating muscle activity, and if so, to measure the distribution of muscle activity within a medial gastrocnemius (MG) muscle. Seven men performed 5 sets of 10 repetitions of a calf-raise exercise with additional 15% of body-weight load. Magnetic resonance images were obtained before and immediately after the exercise. To threshold images, only those pixels showing transverse relaxation time (T2) greater than the mean+1 S.D. of the entire regions of interest (ROIs) in the preexercise image and T2 lower than the mean+1 S.D. of the entire ROIs in the postexercise image were identified. The survived pixels showing T2 are defined as active muscle. Those thresholded images were 3-D reconstructed, and this was used to determine area of active muscle along transverse, longitudinal and vertical axes. At the exercise level used in the present study, the percentage volume of activated muscle in the MG was 62.8+/-4.5%. There was a significant correlation between percentage volume of activated muscle and integrated electromyography (r=.78, P<.05). Percentage areas of activated muscle were significantly larger in the medial than in the lateral region, in the anterior than in the posterior region and in the distal than in the proximal region (P<.05). These results suggest that mfMRI can be used to evaluate the muscle activity and to determine intramuscular variations of activity within skeletal muscle.

Adult↗

Functional MRI of auditory verbal working memory: long-term reproducibility analysis.

Although functional MRI (fMRI) has shown to be a tool with great potential to study the normal and diseased human brain, the large variability in the detected hemodynamic responses across sessions and across subjects hinders a wider application. To investigate the long-term reproducibility of fMRI activation of verbal working memory (WM), eight normal subjects performed an auditory version of the 2-back verbal WM task while fMRI images were acquired. The experiment was repeated nine times with the same settings for image acquisition and fMRI task. Data were analyzed using SPM99 program. Single-session activation maps and multi-subject session-specific activation maps were generated. Regions of interest (ROIs) associated to specific components of verbal WM were defined based on the voxels' coordinates in Talairach space. Visual observation of the multi-subject activation maps showed similar activation patterns, and quantitative analysis showed small coefficients of variance of activation within ROIs over time, suggesting small longitudinal variability of activation. Visual observation of the activation maps of individual sessions demonstrated striking variation of activation across sessions and across subjects, and quantitative analysis demonstrated larger contribution from between-subject variation to overall variation than that from within-subject variation. We concluded that by multi-subject analysis of data from a relatively small number of subjects, reasonably reproducible activation for the 2-back verbal WM paradigm can be achieved. The level of reproducibility encourages the application of this fMRI paradigm to the evaluation of cognitive changes in future investigations. The quantitative estimation of the proportions of within-subject and between-subject variabilities in the overall variability may be helpful for the design of future studies.

Acoustic Stimulation↗

Statistical methods for detecting activated regions in functional MRI of the brain.

Two statistical tests for detecting activated pixels in functional MRI (fMRI) data are presented. The first test (t-test) is the optimal solution to the problem of detecting a known activation signal in Gaussian white noise. The results of this test are shown to be equivalent to the cross-correlation method that is widely used for activation detection in fMRI. The second test (F test) is the optimal solution when the measured data are modeled to consist of an unknown activation signal that lies in a known lower dimensional subspace of the measurement space with added Gaussian white noise. A model for the signal subspace based on a truncated trigonometric Fourier series is proposed for periodic activation-baseline imaging paradigms. The advantage of the second method is that it does not assume any information about the shape or delay of the activation signal, except that it is periodic with the same period as the activation-baseline pattern. The two models are applied to experimental echo-planar fMRI data sets and the results are compared.

Algorithms↗