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[Functional MRI of the human brain responses to olfactory stimulation].

Image artifacts such as signal loss or distortion due to intravoxel phase dispersion at the skull base are problematic in analysis by functional MRI (fMRI). Since the olfactory center of the brain is located in the medial temporal and basal frontal areas, it is a challenge to try to detect the Blood Oxygenation Level Dependent (BOLD) effect during fMRI at olfactory stimulation. We examined 20 normal volunteers with a 1.5-T MR system, employing multishot, interleaved echo-planar imaging (EPI). Olfactory stimulation was performed with 2-methyl-1, 3-cyclo-pentanedione, a caramel-like fragrance, by presenting it for 20 seconds with two cycles of rest-stimulus paradigm. Sites of functional activation were identified by correlation analysis with a threshold of p < 0.01. Most commonly activated areas were the orbitofrontal and primary olfactory cortices. Mild activation was also observed in the cingulate gyrus, lateral temporal cortex, cerebellum, parietal and occipital lobes. These results indicate that olfactory stimulation participates in the emotion and behavior processes. Interestingly, broad activation in the "silent" area of the frontal and temporal lobe was also observed in some cases. Multishot EPI was a useful method to evaluate brain activation at the basal level on fMRI.

Adult↗

Functional MRI of phonological and semantic processing in temporal lobe epilepsy.

Phonological and semantic aspects of language were examined in patients with unilateral temporal lobe epilepsy (TLE) and healthy controls using functional MRI. We expected to replicate previous findings in healthy individuals showing relatively greater activation in frontal regions for phonological compared with semantic processing, and greater activation in temporal regions for semantic compared with phonological processing. We hypothesized that differences between patients with left TLE and healthy controls would be found in the pattern of left temporal cortical activation associated specifically with semantic processing. Patients with right TLE were included as a seizure control group. All TLE patients previously showed left hemisphere language dominance on intracarotid sodium amytal studies. Greater blood oxygen level dependent activation was found during phonological processing compared with semantic processing in frontal regions for healthy participants but, contrary to expectation, semantic processing did not lead to increased temporal lobe activity relative to phonological processing. Furthermore, no differences between left temporal patients and controls were found specifically in left temporal cortex. Rather, patients with left temporal seizure foci showed significantly greater left dorsolateral prefrontal activity compared with controls, as well as increased signal change in left inferior frontal and right middle temporal gyrus. Surprisingly, patients with right, but not left, TLE showed poorer performance on the linguistic tasks compared with controls, as well as a decrease in right superior temporal activation. The results converge with studies of dyslexic patients showing increased left frontal activity in the presence of left temporal dysfunction and are suggestive of both inter- and intra-hemispheric functional reorganization of language representation in left TLE.

Adolescent↗

Functional MRI using sensitivity-encoded echo planar imaging (SENSE-EPI).

Parallel imaging methods become increasingly available on clinical MR scanners. To investigate the potential of sensitivity-encoded single-shot EPI (SENSE-EPI) for functional MRI, five imaging protocols at different SENSE reduction factors (R) and matrix sizes were compared with respect to their noise characteristics and their sensitivity toward functional activation in a motor task examination. At constant echo times, SENSE-EPI was either used to shorten the single volume acquisition times (TR(min)) at matrix size 128 x 100 (22 slices) from 3.9 s (no SENSE) to 2.0 s at R = 3, or to increase the matrix size to 192 x 153 (22 slices), resulting in TR(min) = 5.3 s for R = 2 or TR(min) = 3.4 s for R = 3. At the lower resolution, the bisection of echo train length (R = 2) substantially reduced distortions and blurring, while signal-to-noise and statistical power (measured by cluster size and maximum t value per unit time) were hardly reduced. At R = 3 the additional gain in speed and distortion reduction was quite small, while signal-to-noise and statistical power dropped significantly. With enhanced spatial resolution the time course signal-to-noise was better than expected from theory for purely thermal noise because of a reduced contribution of physiological noise, and statistical power almost reached that of the regular, low-resolution single-shot EPI, with a slight drop off toward R = 3. Thus, SENSE-EPI allows to substantially increase speed and spatial resolution in fMRI. At SENSE reduction factors up to R = 2, the potential drawbacks regarding signal-to-noise and statistical power are almost negligible.

Adult↗

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques.

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high-resolution fast low-angle shot (FLASH) technique (matrix size 1282). The FLASH technique was applied additionally with a 64(2) matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64(2) matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and posterior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 1282 compared to FLASH 64(2) and EPI 64(2), whereas the activated areas proved to be smaller in FLASH 1282 functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 1282. Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.

Adult↗

Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.

Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.

Acoustic Stimulation↗

Correlation between the amplitude of cortical activation and reaction time: a functional MRI study.

OBJECTIVE: We sought to examine the correlation between reaction time and the amplitude of cortical activation during the performance of a visuomotor response-time task in a functional MRI (fMRI) experiment. We hypothesized that the fMRI blood oxygenation level-dependent (BOLD) amplitude may have a negative correlation with a subject's reaction time: the lower the amplitude within the cortical areas along the visuomotor pathway, the slower the response. A larger amplitude of the fMRI signal would reflect faster response times. SUBJECTS AND METHODS: During a single-event fMRI experiment, the reaction times (in milliseconds) of 32 right-handed subjects responding to a visual cue were recorded. Analysis of the single-event paradigm using Statistical Parametric Mapping (SPM99) was performed, activation maps were produced for each subject, and then a random effects group analysis was performed. The maximum amplitudes of cortical activation (percent signal change) in four activated cortical regions were estimated and tabulated. The regions of interest included were the right and left occipital visual cortices, the supplementary motor area, and the left sensorimotor area. Simple and multiple regressions were performed between the mean reaction times of the subjects and the BOLD amplitudes in each region of interest and for the composite region of interest. RESULTS: The results showed significant negative associations between the reaction times and maximum amplitudes in the right occipital, left occipital, and left sensorimotor area cortical regions (p < 0.05). However, no significant association was found between reaction times and the amplitude within the supplementary motor area. When the effects of age and sex on these associations were analyzed, we found that age had an impact on the results for individual regions of interest in the left occipital and left sensorimotor areas, but the composite amplitude of activation remained significantly correlated with reaction times. CONCLUSION: The degree of signal change in BOLD fMRI response of the right occipital, left occipital, and left sensorimotor areas reflects the speed of performance during the visuomotor response time task by the subject. Thus, the amplitude of activation can be used as one parameter to assess change in function.

Adult↗

Broca's area and the discrimination of frequency transitions: a functional MRI study.

The left inferior frontal lobe has been traditionally viewed as a "language area," although its involvement in the discrimination of rapid nonverbal frequency changes has been also shown. Using functional MRI, we studied seven healthy adults during discrimination of relatively slow (200 ms) tonal frequency glides. Compared to a control task, in which subjects indiscriminately responded to white noise bursts, tonal discrimination was associated with bilateral superior and middle temporal and medial frontal activations. Inferior frontal activations were bilateral, but stronger on the left. Contrary to previous studies comparing discrimination of slow frequency changes to rest, our results suggest that such discriminations-when compared to an auditory control task-activate the left inferior frontal gyrus. Our findings are consistent with a participation of Broca's area in nonlinguistic processes besides its known roles in semantic, syntactic, and phonological functions.

Adult↗

Comparison of functional MRI image realignment tools using a computer-generated phantom.

This study discusses the development of a computer-generated phantom to compare the effects of image realignment programs on functional MRI (fMRI) pixel activation. The phantom is a whole-head MRI volume with added random noise, activation, and motion. It allows simulation of realistic head motions with controlled areas of activation. Without motion, the phantom shows the effects of realignment on motion-free data sets. Prior to realignment, the phantom illustrates some activation corruption due to motion. Finally, three widely used realignment packages are examined. The results showed that the most accurate algorithms are able to increase specificity through accurate realignment while maintaining sensitivity through effective resampling techniques. In fact, accurate realignment alone is not a powerful indicator of the most effective algorithm in terms of true activation.

Adult↗

Rapid self-paced event-related functional MRI: feasibility and implications of stimulus- versus response-locked timing.

Many cognitive paradigms require self-paced responses or examine events that occur at unpredictable times. To explore whether functional MRI (fMRI) can accommodate such paradigms, a method allowing rapid, unpredictable trial pacing was developed and tested on 17 subjects using activation of the motor network as a model. Trial onset was determined solely by the subjects' self-paced responses and trials occurred, on average, less than 2 s apart. The hemodynamic response was estimated both in relation to stimulus onset (stimulus-locked) and in relation to behavioral response time (response-locked). Results yielded robust activation maps and hemodynamic response estimates. Specifically, significant activation in motor cortex, supplementary motor area (SMA), and cerebellum was observed both at the group and at the individual-subject level, confirming predicted patterns of brain activity. Moreover, the self-paced design resulted in even temporal sampling of the hemodynamic response across the image acquisition, allowing estimation of response parameters. Stimulus-locked analysis demonstrated strong correlation between hemodynamic- and behavioral-response timing both within and across subjects. Conversely, response-locked analysis showed minimal correlation with behavioral timing, suggesting effective resynchronization of the timing parameters. These results demonstrate fMRI procedures that can accommodate rapid, arbitrarily timed events and, in doing so, provide precise temporal estimates of the hemodynamic response.

Adult↗

EEG quality during simultaneous functional MRI of interictal epileptiform discharges.

This article concerns the evaluation of the quality of interictal epileptiform EEG discharges recorded throughout simultaneous echo planar imaging (EPI). BOLD (blood oxygen level dependent) functional MRI (fMRI) images were acquired continuously on a patient with intractable epilepsy. EEG was sampled simultaneously, during and after imaging, with removal of pulse and imaging artifacts by subtraction of channel-specific running averages. Contiguous EEG epochs recorded with and without fMRI (fMRI+ve vs. fMRI-ve) were next randomized and presented to two blinded observers. Epileptiform discharges were identified retrospectively, and comparison was made in terms of the number of identified events, their amplitude, and spatiotemporal distribution. A spectral analysis was also performed on the EEG. In the randomized comparison of EEG segments, 80 (fMRI+ve) vs. 69 (fMRI-ve) discharges were noted with good interobserver agreement (69%). There were no significant differences in amplitude or spatio-temporal distribution. Comparison of the events detected and measured by two expert observers demonstrated that the Interictal Epileptiform Discharge (IED) characteristics were indistinguishable with and without scanning. We review briefly the existing literature on EEG recording quality for combined EEG/fMRI.

Artifacts↗

Right hemispheric dominance of inhibitory control: an event-related functional MRI study.

Normal human behavior and cognition are reliant on a person's ability to inhibit inappropriate thoughts, impulses, and actions. The temporal and spatial advantages of event-related functional MRI (fMRI) were exploited to identify cortical regions that showed a transient change in fMRI signal after the withholding of a prepotent motor response. The temporal specificity of the event-related fMRI design also minimized possible contamination from response inhibition errors (i. e., commission errors) and other extraneous processes. Regions identified were strongly lateralized to the right hemisphere and included the middle and inferior frontal gyri, frontal limbic area, anterior insula, and inferior parietal lobe. Contrary to the prominence traditionally given to ventral frontal regions for response inhibition, the results suggest that response inhibition is accomplished by a distributed cortical network.

Adult↗

Functional MRI follow-up study of language processes in healthy subjects and during recovery in a case of aphasia.

BACKGROUND AND PURPOSE: The goal of this study was to develop a functional MRI (fMRI) paradigm robust and reproducible enough in healthy subjects to be adapted for a follow-up study aiming at evaluating the anatomical substratum of recovery in poststroke aphasia. METHODS: Ten right-handed subjects were studied longitudinally using fMRI (7 of them being scanned twice) and compared with a patient with conduction aphasia during the first year of stroke recovery. RESULTS: Controls exhibited reproducible activation patterns between subjects and between sessions during language tasks. In contrast, the patient exhibited dynamic changes in brain activation pattern, particularly in the phonological task, during the 2 fMRI sessions. At 1 month after stroke, language homotopic right areas were recruited, whereas large perilesional left involvement occurred later (12 months). CONCLUSIONS: We first demonstrate intersubject robustness and intrasubject reproducibility of our paradigm in 10 healthy subjects and thus its validity in a patient follow-up study over a stroke recovery time course. Indeed, results suggest a spatiotemporal poststroke brain reorganization involving both hemispheres during the recovery course, with an early implication of a new contralateral functional neural network and a later implication of an ipsilateral one.

Acoustic Stimulation↗

Spatial working memory in obsessive-compulsive disorder improves with clinical response: A functional MRI study.

To date, only a few studies have examined whether executive dysfunctions in obsessive-compulsive disorder (OCD) are state or trait dependent and almost none of these studies have used functional neuroimaging techniques. We conducted a functional MRI study before and after 12 weeks of pharmacological treatment in 14 psychotropic-free patients with OCD without comorbidity. Subjects performed a spatial variant of a working memory task with four increasing levels of difficulty (n-back task). Responders and non-responders did not differ in clinical and demographical characteristics or brain activation patterns before treatment. Performance improved only in responders and was associated with a change in the overall pattern of brain activity during the task. We found no correlations between (changes in) scores on symptom scales, brain activity and performance. Our preliminary findings suggests that spatial working memory deficits in OCD and their functional anatomical correlates, as assessed with a spatial n-back task, are, at least to some extent, state dependent.

Adult↗

Functional MRI activation of somatosensory and motor cortices in a hand-grafted patient with early clinical sensorimotor recovery.

The aim of this study was to investigate somatosensory and motor cortical activity with functional MRI (fMRI) in a hand-grafted patient with early clinical recovery. The patient had motor fMRI examinations before transplantation, and motor and passive tactile stimulations after surgery. His normal hand and a normal group were studied for comparison. A patient with complete brachial plexus palsy was studied to assess the lack of a fMRI signal in somatosensory areas in the case of total axonal disconnection. Stimulating the grafted hand revealed significant activation in the contralateral somatosensory cortical areas in all fMRI examinations. The activation was seen as early as 10 days after surgery; this effect cannot be explained by the known physiological mechanisms of nerve regeneration. Although an imagination effect cannot be excluded, the objective clinical recovery of sensory function led us to formulate the hypothesis that a connection to the somatosensory cortex was rapidly established. Additional cases and fundamental studies are needed to assess this hypothesis, but several observations were compatible with this explanation. Before surgery, imaginary motion of the amputated hand produced less intense responses than executed movements of the intact hand, whereas the normal activation pattern for right-handed subjects was found after surgery, in agreement with the good clinical motor recovery.

Adult↗

[Diffusion, perfusion and activation functional MRI studies of brain arteriovenous malformations].

The management of Brain Arteriovenous Malformations continues to be challenged by a lack of understanding and control of pathophysiological processes implied in the clinical symptoms. New data from functional MRI with diffusion-weighted, perfusion-weighted and neuronal activation highlight abnormal brain areas near or remote to the AVM nidus. Moreover, these techniques are able to show hemodynamic and neuronal adaptative phenomena involved in brain plasticity. They reflect the instantaneous hemodynamic brain conditions that may help to correlate the clinical symptoms with the anatomical and functional substratum and to influence any invasive therapy.

Brain↗

Comparison of spike-triggered functional MRI BOLD activation and EEG dipole model localization.

We studied six patients with localization-related epilepsy, frequent interictal epileptiform discharges, and positive spike-triggered blood oxygen level-dependent functional MRI (BOLD-fMRI) findings. EEG source analysis solutions based on 64-channel EEG recorded in a separate session outside the scanner were obtained using dipole models and compared to the BOLD localization. The BOLD and structural images were coregistered, allowing the measurement of distances between the generator models and BOLD activation(s) and structural lesion when present. In all cases dipole models could be found that explained a sufficient amount of the data and that were anatomically concordant with the BOLD localization. In the five cases with structural abnormality visible on T1 scans, the BOLD activation overlapped or was in close proximity to the abnormality. The overall mean distance between the main moving dipole and the center of the nearest BOLD activation was 3.5 and 2.2 cm for the negative and positive peaks, respectively, including one case of a deep BOLD activation, in which the distance was 5 cm. In conclusion, the degree of agreement between the BOLD and EEG source localization indicates that the combination of these two noninvasive techniques offers the possibility of advancing the study of the generators of epileptiform electrical activity.

Adult↗

The lag of cerebral hemodynamics with rapidly alternating periodic stimulation: modeling for functional MRI.

A mathematical model that characterizes the response of venous oxygenation to changes in cerebral blood flow (rCBF) and oxygen consumption has been previously presented. We use this model to examine the dampening phenomenon in functional MRI (fMRI) signals with rapidly alternating periodic stimulation bursts. Using a mass balance approach, the equations for an input-output model are derived and solved using Matlab (the Math Works Inc.). Changes in venous oxygenation are related to the results of fMRI experiments using progressively shorter periods of stimulation. An impulse-response function for the model is derived in an attempt to explore the source of the lag in cerebral hemodynamics. Increasing the frequency of stimulation bursts eventually produces a dampening in the fMRI signal. The dampening phenomenon in fMRI signals occurs with stimulation of high frequency on-off alternation. The dynamics of signal dampening, as well as the impulse-response function of a blood oxygen level-dependent model, lend strong indirect support to the hypothesis that blood oxygen level-dependent contrast at the level of the venous blood pool, rather than R1 inflow effects or changes in oxygenation at the level of the capillary bed, underlies the observed signal changes in fMRI.

Blood Flow Velocity↗

Brain reorganization during attention and memory tasks in multiple sclerosis: insights from functional MRI studies.

Deficits in memory and attention frequently occur during the course of multiple sclerosis (MS). In patients with MS the severity of cognitive manifestations is not closely related to indices of structural brain damage on both conventional and non conventional magnetic resonance imaging (MRI). It is conceivable that the ability of the brain to compensate for tissue impairment or loss may contribute to the maintenance of normal performance despite scattered brain lesions. Accordingly, using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of brain activation during motors tasks than controls. Changes in functional organization of the cerebral cortex have also been reported by fMRI studies comparing the activation patterns during cognitive tasks in patients with MS and in healthy subjects. Differences in patients' selection, activation paradigm, experimental design and MR acquisition parameters make, however, the results obtained from fMRI studies difficult to be compared and may explain, at least partially, some discrepant findings. Nevertheless, fMRI studies provide a new interesting way of understanding how the brain can change its functional organization in response to MS pathology, and might be useful in the study of the effects of either rehabilitation or pharmacological agents on brain plasticity.

Attention↗