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Functional MRI localizing in the cerebellum.

Mapping of cerebellar function by functional MRI now enables us not only to re-establish older anatomic findings of somatotopic representations but to gain new insights in the function of the cerebellum and its intimate relations of cerebral regions to serving sensorimotor function, sensory discrimination, and cognitive processing. Consequently, it will change our understanding of neurologic and psychologic failures in patients with inborn errors or neurodegenerative diseases or after neurosurgical procedures.

Brain Mapping↗

Functional MRI experiments: acquisition, analysis and interpretation of data.

Functional MRI is widely used to address basic and clinical neuroscience questions. In the key domains of fMRI experiments, i.e. acquisition, processing and analysis, and interpretation of data, developments are ongoing. The main issues are sensitivity for changes in fMRI signal that are associated with brain function, and the design of tasks with which brain functions are invoked. In this paper we address these issues, in terms of strengths, weaknesses and future developments. Acquisition of data is commonly achieved with techniques that measure blood oxygen level-dependent (BOLD) signal changes. Although the mechanisms that affect BOLD signal are complex and not well understood, fMRI yields results that agree with known functional topography. Sensitivity for task-related brain activity is expected to benefit from technological advances in acquisition, i.e. SENSE or parallel imaging, and higher field scanners (3 T). Data analysis is geared towards modelling sources of signal variation, i.e. reducing noise in the data time-series, and the cerebrovascular response to task-related changes in neuronal activity. Analytical algorithms such as connectivity and component analysis contribute to the extraction of meaningful information from fMRI datasets. The choice of tasks, and consequently of the statistical evaluation procedures, is best guided by the specific questions that are formulated a priori. The future is expected to bring more sophisticated questions, and tasks that allow for accurate modelling of involved brain functions. An example of a hypothesis-driven experiment is presented, where we investigated whether practise of a working memory task caused a shift in the neuronal representation of working memory or not.

Brain↗

Motor cortex localization using functional MRI and transcranial magnetic stimulation.

OBJECTIVE: Congenital brain lesions producing focal seizures may be accompanied by reorganization of the areas responsible for motor and sensory functions within the brain due to a phenomenon that has been termed "neuronal plasticity." This can be studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Using either method, the motor cortex can be localized noninvasively, but to date there have been few studies correlating the level of agreement between the two techniques. METHODS: We used fMRI and TMS to localize the motor cortex in a young woman with intractable focal seizures, congenital left arm weakness, and a dysplastic right hemisphere on MRI. RESULTS: There was excellent agreement in the localization of motor representation for each hand. Both were predominantly located in the left hemisphere. fMRI also showed an area of posterior activation in the right hemisphere, but there was no evidence of descending corticospinal projections from this site using TMS, direct cortical stimulation, and Wada testing. CONCLUSIONS: Functional MRI (fMRI) and transcranial magnetic stimulation (TMS) were successfully used to localize cortical motor function before epilepsy surgery. Each technique demonstrated migration of motor function for the left hand to the left motor cortex. After resection of the dysplastic right precentral gyrus there was no permanent increase in weakness or disability. The two techniques are complementary; fMRI indicates all cortical areas activated by the motor task, whereas TMS identifies only those areas giving rise to corticospinal projections.

Adult↗

Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes.

Functional neuroimaging studies of episodic recognition memory consistently demonstrate retrieval-associated activation in right prefrontal regions, including the right anterior and right dorsolateral prefrontal cortices. In theory, these activations could reflect processes associated with retrieval success, retrieval effort or retrieval attempt; each of these hypotheses has some support from previous studies. In Experiment 1, we examined these functional interpretations using functional MRI to measure prefrontal activation across multiple levels of recognition performance. Results revealed similar patterns of right prefrontal activation across varying levels of retrieval success and retrieval effort, suggesting that these activations reflect retrieval attempt. Retrieval attempt may include initiation of retrieval search or evaluation of the products of retrieval, such as scrutiny of specific attributes of the test item in an effort to determine whether it was encountered previously. In Experiment 2, we examined whether engagement of retrieval attempt is context-dependent by varying the context in which retrieval was performed; this was done by changing test instructions. Importantly, study and test stimuli were held constant, with only the test instructions varying across conditions. Results revealed that the pattern of right prefrontal activation varied across retrieval contexts. Collectively, these experiments suggest that right prefrontal regions mediate processes associated with retrieval attempt, with the probability of engaging these regions depending upon the retrieval context. Conflicting results across previous studies may be reconciled if the influence of retrieval context on the adopted retrieval strategy is considered. Finally, these results suggest that right prefrontal regions activated during recognition are not critical for successful performance as similar magnitudes of activation were present across multiple levels of performance. These findings reconcile imaging results with the selective effects of prefrontal lesions on retrieval-intensive episodic memory tests.

Adolescent↗

Functional MRI with variable echo time acquisition.

A new functional MRI protocol that integrates variable echo time (TE) acquisition and a block-design paradigm is proposed and evaluated with finger-tapping motor task. Simulations and experimental data show that the blood oxygenation level-dependent (BOLD) sensitivity achieved with this approach is comparable to that achieved using a conventional constant-TE protocol. The proposed variable-TE fMRI protocol provides valuable information that cannot be obtained with the constant-TE protocol. First, a field inhomogeneity map can be derived from the multi-TE data and used to correct EPI geometric distortions. Second, changes of T2* values due to the BOLD effect can be quantified. Third, for brain regions with pronounced susceptibility field gradients, the reduced BOLD sensitivity may be compensated for when the acquired multi-TE data are processed appropriately (e.g., with weighted summation). Fourth, large venules and veins may possibly be identified (depending on the vessel orientation and volume fraction) by evaluating the phase values of the multi-TE data. Finally, magnetic field drift over time can be measured from dynamic field maps available with this protocol.

Algorithms↗

[Motor functional MRI by spiral scan--compared with GRE].

Recently, functional MRI (fMRI) has been performed in two methods using 1.5 tesla machine. One was performed using gradient recalled echo (GRE), the other was performed using echo planner imaging (EPI). There is a third method for fMRI called spiral scan. This method is applicable without strong gradient magnetic field such as required by EPI. In this study, motor fMRI was performed in ten normal volunteers by both spiral scan and GRE. Less than 1% risk (t-test), spiral scan showed the reactive area more clearly than GRE. And GRE showed higher signal intensity changing ratio than spiral scan, but there was no significant difference between spiral scan and GRE. The acquisition time of spiral scan was 2 seconds per image, and that of GRE was 10.5 seconds. Spiral scan has good temporal resolution and contrast-noise ratio. These are very advantageous for fMRI.

Adult↗

Retrospective estimation and correction of physiological fluctuation in functional MRI.

Image-to-image fluctuation due to physiological motion is a major limitation to the accurate detection of neuronal activity with functional MRI. In this paper, a new and general technique for the estimation and compensation of the physiological effects is presented. By simultaneously monitoring the respiration and heart beat during the acquisition of imaging data, and retrospectively synchronizing the imaging data with physiological activity, physiological effects are estimated and removed. This technique does not rely on the periodicity of the respiration or the heart beat, does not affect the signal changes arising from neuronal activation, and is beneficial to images acquired with any speed. Experimental studies performed with FLASH and EPI sequences have demonstrated that the new technique is effective in reducing physiological fluctuation and improving the sensitivity of functional MRI and is generally applicable.

Algorithms↗

Evaluation of respiratory artifact correction techniques in multishot spiral functional MRI using receiver operator characteristic analyses.

Navigator corrections and low-spatial frequency (LSF) oversampling are investigated as methods for reducing respiration-related effects in multishot functional MRI. Both techniques take advantage of the smoothly varying or nearly constant phase variations linked to the respiration cycle. These techniques were tested in functional MRI studies with spiral k-space acquisitions. Receiver operator characteristic (ROC) analyses and the temporal variance averaged across the brain were used to evaluate their effectiveness. Both methods were found to increase the area under the ROC curve and to reduce the standard deviation, with the LSF oversampling method being more effective.

Artifacts↗

Local vascular CO2 reactivity in the infant brain assessed by functional MRI.

The local cerebral vascular response to hyperventilation was investigated in five distressed, intubated infants by means of a T2 sensitive gradient-echo MRI technique at 1.5 T. In one preterm infant, the MR signal change during hyperventilation was sparse. In four term infants, the mean MR signal of the brain slice investigated decreased by 1.2-2.6% per kPa change in PCO2 as a reflection of decreased cerebral blood flow during hyperventilation. Pixel-wise analysis revealed absence of vascular response in the basal ganglia, the thalamus or in the occipital region. In two adult controls, who hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional MRI.

Adult↗

Functional MRI for presurgical planning: problems, artefacts, and solution strategies.

OBJECTIVES: Presurgical mapping of motor function is a widely used clinical application of functional (f) MRI, employing the blood oxygenation level dependent contrast. The aim of this study was to report on 3 years experience of 194 fMRI studies on the representation of motor function in 103 patients and to describe the problems and artefacts that were typically present. METHODS: An evaluation was carried out to determine whether the patients' age, type or location of the tumourous lesion, severity of the paresis, or the tasks used during the investigation have an effect on artefacts of fMRI studies and how these artefacts are best overcome. RESULTS: Functional MRI identified the motor regions in 85% of all investigated paradigms. In 11% of the investigated patients no information at all on functional localisation was obtained. A draining vein within the central sulcus was present in all patients that showed activation within the parenchyma of the precentral gyrus but also in three patients in whom no parenchymal activation was present. Head movement artefacts were the most frequent cause for fMRI failure, followed by low signal to noise ratio. Motion artefacts were correlated with the degree of paresis and with the functional task. Tasks involving more proximal muscles led to significantly more motion artefacts when compared with tasks that primarily involved distal muscles. Mean MR signal change during task performance was 2.5%. CONCLUSIONS: Most of the artefacts of functional MRI can be reliably detected and at least in part be reduced or eliminated with the help of mathematical algorithms, appropriate pulse sequences and tasks, and-probably most important-by evaluating the fMRI raw data-that is, the MR signal time courses.

Adolescent↗

Modeling the hemodynamic response in single-trial functional MRI experiments.

Today, most studies of cognitive processes using functional MRI (fMRI) experiments adopt a single-trial design. Highly flexible stimulation paradigms require new statistical models in which not only the activation amount but also the time course of the measured hemodynamic response is analyzed. Most previous approaches have been based on a linear regression context and have introduced hemodynamic model functions to improve the signal detection. In this report a nonlinear regression context is derived, from which shape parameters for the hemodynamic response are obtained per trial and per region of interest. These parameters allow the investigation of stimulus-induced shape variations of the hemodynamic response. By embedding the estimation into a robust statistical framework and rigorously analyzing the spatiotemporal interactions in the fMRI data, it is possible to derive statistically valid descriptions of single hemodynamic responses. The model, estimation algorithm, validation, and an example analysis from a single-trial fMRI study are reported. Magn Reson Med 42:787-797, 1999.

Algorithms↗

[Heschl's gyrus identification using functional MRI: neurosurgical issue].

AIM: Localizing Heschl's gyrus with functional MRI (fMRI) is a particularly difficult challenge due to the noise of the echo planar sequences and the frequent activation of language areas during auditory paradigms. The goal of this study was to search for a paradigm capable of assessing only pure primary auditory cortex activation with fMRI. MATERIAL AND METHOD: Ten healthy adults were studied. Subjects were asked to continuously perform a visual decisional task while passively listening to an ON-OFF randomized paradigm of tones and rhythmic stimuli. Data were analyzed with SPM. RESULTS: Auditory cortex activation was assessed by observing activated pixels in functional images. Due to the distraction effect of the visual decisional task, functional images of pure primary auditory cortex were obtained in all subjects, with strong and selective activation in the Heschl's gyrus. CONCLUSION: This technique, coupled with fMRI data of language areas can be used as a preoperative tool for surgical preplanning in the left superior temporal region. It shows a clear distinction between resectable areas (primary auditory cortex) and not resectable essential areas (language areas).

Acoustic Stimulation↗

Determination of language dominance using functional MRI: a comparison with the Wada test.

We performed functional MRI (FMRI) in 22 consecutive epilepsy patients undergoing intracarotid amobarbital (Wada) testing and compared language lateralization measures obtained with the two procedures. FMRI used a single-word semantic decision task previously shown to activate lateralized language areas in normal adults. Correlation between the two tests was highly significant (r = 0.96; 95% CIs 0.90 to 0.98; p < 0.0001). These results validate the FMRI technique and suggest that "active" areas observed with this semantic processing task correspond to those underlying hemispheric dominance for language. This strong correlation observed supports the view that language lateralization is a continuous rather than a dichotomous variable. In addition to lateralization information, FMRI consistently demonstrated focal regions of activity in lateral frontal and temporo-parieto-occipital cortex. These functional maps may be helpful in defining the boundaries of surgical excisions.

Adolescent↗

Brain activation during silent word generation evaluated with functional MRI.

This is a study of word generation during functional MRI (fMRI). Eleven normal healthy subjects were instructed to generate words covertly, (i.e., silently) that began with particular letters. Images were acquired on a conventional 1.5T scanner at three contiguous axial planes encompassing language-related areas of the temporal and frontal lobe. The data were analyzed at the level of a Talairach box, after individually fitting the proportional Talairach grid system to each slice. The main variable of interest was the number of activated pixels within a Talairach box. Boxes with a significant increase in the proportion of activated pixels were located in three regions of the left neocortex: (1) Brodmann areas 44 and 45 in the dorsolateral frontal cortex (Broca's area), (2) areas 21 and 37 in the temporal cortex, (3) and the striate/extrastriate cortex (areas 17 & 18). The results are discussed in terms of a cognitive model of word generation and are compared, in detail, with the results of prior relevant imaging studies.

Adolescent↗

Motor functional MRI for pre-operative and intraoperative neurosurgical guidance.

Functional MRI (fMRI) may provide a means of locating areas of eloquent cortex that can be used to guide neurosurgeons in their quest to maximize intracerebral tumour resection whilst minimizing post-procedural neurological deficits. This work aimed to develop and provide an initial assessment of such a technique. 19 patients with mass lesions close to the primary motor cortex underwent fMRI at 1.5T. A single shot echo planar technique was used to acquire data corresponding to right and left hand movement. Resultant activation maps were used to aid pre-surgical planning. Data was used in conjunction with an intraoperative navigation system in 13 cases. Activation was attributed to primary motor, primary somatosensory or supplementary motor cortex in 17 of 19 subjects. No permanent changes in motor deficit were detected post surgery. The additional information provided by fMRI, particularly when incorporated into a neuronavigation guided craniotomy, was deemed highly valuable to the neurosurgeon as it enabled safe resection of tumour in anatomical locations previously deemed to be too high risk for safe resection using conventional (non-fMRI-guided) technique. This observation is reinforced by the fact that no patients suffered permanent neurological deficit after radical tumour debulking (surgical estimates >90% tumour resection).

Adolescent↗

Spatio-temporal imaging of focal interictal epileptiform activity using EEG-triggered functional MRI.

EEG-triggered, blood oxygen level-dependent functional MRI (BOLD-fMRI) was used in 24 patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes) to identify those brain areas involved in generating the spikes, and to study the evolution of the BOLD signal change over time. The location of the fMRI activation was compared with the scalp EEG spike focus and the structural MR abnormality. Twelve patients (50%) had an fMRI activation concordant with the EEG focus and structural brain abnormalities where present (n = 7). In 2 other patients, the fMRI activation was non-concordant with electroclinical findings. The remaining 10 patients (41.7%) showed no significant fMRI activation. These patients had significantly lower mean spike amplitudes compared to those with positive fMRI results (p = 0.03). The time course of the BOLD response was studied in 3 patients and this revealed a maximum signal change 1.5 to 7.5 sec after the spike. In conclusion, EEG-triggered fMRI can directly identify the generators of interictal epileptiform activity, with high spatial resolution, in selected patients with frequent spikes. The superior spatial resolution obtainable through EEG-triggered fMRI may provide an additional non-invasive tool in the presurgical evaluation of patients with intractable focal seizures.

Action Potentials↗

Multiresolution data acquisition and detection in functional MRI.

In an investigation of a multiresolution and multistaged approach in functional MRI, the relationship between spatial resolution and detection of functional activation is examined. The difference between functional detection and mapping is defined, and a multiresolution approach to functional detection is analyzed by constructing simple theoretical and experimental models simulating variations of in-plane resolution. Experimentally measured blood oxygenation level-dependent (BOLD) signal changes as well as BOLD contrast-to-noise ratio (CNR) with respect to different spatial resolutions are compared with results from theoretical predictions and simulation. From both an experimental and a theoretical perspective, it is shown that BOLD CNR and, thus, the concomitant detection of the functional activation are maximized when the resolution matches the size of activation.

Adult↗

The application of functional MRI of memory in temporal lobe epilepsy: a clinical review.

Functional MRI (fMRI) is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions. Since its introduction, there has been considerable speculation regarding the role it may play in the presurgical assessment of temporal lobe epilepsy (TLE). This review considers the progress made to date in using fMRI to investigate memory processing in the medial temporal lobe in normal subjects and in those with TLE. Results so far suggest that fMRI will be incorporated into the presurgical assessment of TLE in the coming years to improve definition of eloquent cerebral areas, with the objective of minimizing the adverse cognitive sequelae of anterior temporal lobe resection.

Brain Mapping↗