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Event-related functional MRI: past, present, and future.

The past two decades have seen an enormous growth in the field of human brain mapping. Investigators have extensively exploited techniques such as positron emission tomography and MRI to map patterns of brain activity based on changes in cerebral hemodynamics. However, until recently, most studies have investigated equilibrium changes in blood flow measured over time periods upward of 1 min. The advent of high-speed MRI methods, capable of imaging the entire brain with a temporal resolution of a few seconds, allows for brain mapping based on more transient aspects of the hemodynamic response. Today it is now possible to map changes in cerebrovascular parameters essentially in real time, conferring the ability to observe changes in brain state that occur over time periods of seconds. Furthermore, because robust hemodynamic alterations are detectable after neuronal stimuli lasting only a few tens of milliseconds, a new class of task paradigms designed to measure regional responses to single sensory or cognitive events can now be studied. Such "event related" functional MRI should provide for fundamentally new ways to interrogate brain function, and allow for the direct comparison and ultimately integration of data acquired by using more traditional behavioral and electrophysiological methods.

Brain↗

Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study.

BACKGROUND: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. METHODS: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. RESULTS: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. CONCLUSIONS: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

Adult↗

The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI.

Research on the prefrontal cortex (PFC) of monkeys and humans indicates that this region supports a heterogeneous repertoire of mental processes that contribute to many complex behaviors, such as working memory. Anatomical evidence for some of these processes derives from functional neuroimaging experiments using blocked experimental designs, which average signal across all components of many trials and therefore cannot dissociate distinct processes with different time courses. Using event-related functional MRI, we were able to isolate temporally the neural correlates of processes contributing to the target presentation, delay, and probe portions of an item-recognition task. Two types of trials were of greatest interest: those with Recent Negative probes that matched an item from the target set of the previous, but not the present, two trials, and those with Nonrecent Negative probes that did not match a target item from either the present or the two previous trials. There was no difference between the two trial types in target presentation (i.e., encoding) or delay-period (i.e., active maintenance) PFC activation, but there was significantly greater activation for Recent Negatives than Nonrecent Negative activation associated with the probe period within left ventrolateral PFC. These findings characterize spatially and temporally a proactive interference effect that may reflect the operation of a PFC-mediated response-inhibition mechanism that contributes to working memory performance.

Adult↗

Functional MRI of the supplementary motor area: comparison of motor and sensory tasks.

PURPOSE: The purpose of this work was to assess the activation of the supplementary motor area (SMA) during simple motor, complex motor, hot sensory, and touch sensory tasks. METHOD: Functional MRI (fMRI) was performed in eight right-handed healthy volunteers. There were four tasks: simple motor, complex motor, hot sensory, and touch sensory. The number of pixels and the average percentage change of signal intensity in the activated SMA were obtained during the four tasks and then compared. RESULTS: The SMA was consistently activated on fMRI during both motor and sensory tasks. The average number of activated pixels during the complex motor task was more than the number during the hot sensory task, but the difference was not statistically significant. The average number of activated pixels during the complex motor task was greater than during the simple motor task. The average number of activated pixels during the hot sensory task was greater than during the touch sensory task. The average percentage change of signal intensity was statistically significant between the simple motor and the complex motor task. The average percentage change of signal intensity was not statistically significant between the complex motor and the hot sensory task. CONCLUSION: The SMA is activated in both motor and sensory tasks. The degree of activation of the SMA differs according to the type of task.

Adult↗

Functional MRI study of the cognitive generation of affect.

OBJECTIVE: The authors investigated, by whole brain functional magnetic resonance imaging (MRI), the neural substrate underlying processing of emotion-related meanings. METHOD: Six healthy subjects underwent functional MRI while viewing 1) alternating blocks of pairs of pictures and captions evoking negative feelings and the same materials irrelevantly paired to produce less emotion (reference pairs); 2) alternating blocks of picture-caption pairs evoking positive feelings and the same materials irrelevantly paired to produce less emotion; and 3) alternating blocks of picture-caption pairs evoking positive feelings and picture-caption pairs evoking negative feelings. RESULTS: Compared with the reference picture-caption pairs, negative pairs activated the right medial and middle frontal gyri, right anterior cingulate gyrus, and right thalamus. Compared with the reference picture-caption pairs, positive pairs activated the right and left insula, right inferior frontal gyrus, left splenium, and left precuneus. Compared with the negative picture-caption pairs, positive pairs activated the right and left medial frontal gyri, right anterior cingulate gyrus, right precentral gyrus, and left caudate. CONCLUSIONS: Contrasts of both 1) negative and reference picture-caption pairs and 2) positive and negative picture-caption pairs activated networks involving similar areas in the medial frontal gyrus (Brodmann's area 9) and right anterior cingu-late gyrus (areas 24 and 32). The area 9 sites activated are strikingly similar to sites activated in related positron emission tomography experiments. Activation of these same sites by a range of evoked affects, elicited by different methods, is consistent with areas within the medial prefrontal cortex mediating the processing of affect-related meanings, a process common to many forms of emotion production.

Adult↗

Functional MRI detects posterior shifts in primary sensorimotor cortex activation after stroke: evidence of local adaptive reorganization?

BACKGROUND AND PURPOSE: Further recovery from stroke can occur late, long after the end of the apparent evolution of pathological changes. This observation and evidence obtained from functional imaging for altered patterns of activation after brain injury suggest that cortical reorganization may contribute to recovery. Here, we have tested for potentially adaptive reorganization in the primary sensorimotor cortex. METHODS: We used functional MRI to study brain activation with dominant hand movement in right-handed healthy control subjects (n=20) and in patients after subcortical ischemic infarcts causing mild to moderate right hemiparesis (n=8). The numbers of pixels activated above threshold and the geometric centers of activation clusters were determined. RESULTS: Although random-effects analysis identified some differences in activation maxima, similar regions of the brain were activated with sequential finger tapping in the patient and control groups. However, consistent with the heterogeneity in the locations, sizes, and times after the infarcts, patterns and magnitudes of activation showed some heterogeneity between patients. Nonetheless, for the group as a whole, there was a decreased motor cortex lateralization index (-0.1+/-0.7 in patients and 0.7+/-0.3 in control subjects, P=0.05). The geometric center of activation of the primary sensorimotor cortex activation cluster contralateral to the affected hand in patients was also shifted posteriorly (mean 12 mm, P<0.04) relative to that of the control subjects. To confirm the latter observation, the activation response with a simple hand-tapping task was examined in some of the subjects. With this task, there was also a trend (mean 10 mm, P=0.07) toward a more posterior activation in patients. CONCLUSIONS: These results confirm altered patterns of activation in the contralateral and ipsilateral primary sensorimotor cortices after recovery from strokes causing hemiparesis. These (and other changes) suggest that modulation of widely distributed parts of the cortical network for motor control may contribute to adaptations leading to functional recovery after stroke.

Acute Disease↗

Cortical language activation in stroke patients recovering from aphasia with functional MRI.

BACKGROUND AND PURPOSE: Two mechanisms for recovery from aphasia, repair of damaged language networks and activation of compensatory areas, have been proposed. In this study, we investigated whether both mechanisms or one instead of the other take place in the brain of recovered aphasic patients. METHODS: Using blood oxygenation level-dependent functional MRI (fMRI), we studied cortical language networks during lexical-semantic processing tasks in 7 right-handed aphasic patients at least 5 months after the onset of left-hemisphere stroke and had regained substantial language functions since then. RESULTS: We found that in the recovered aphasic patient group, functional language activity significantly increased in the right hemisphere and nonsignificantly decreased in the left hemisphere compared with that in the normal group. Bilateral language networks resulted from partial restitution of damaged functions in the left hemisphere and activation of compensated (or recruited) areas in the right hemisphere. Failure to restore any language function in the left hemisphere led to predominantly right hemispheric networks in some individuals. However, better language recovery, at least for lexical-semantic processing, was observed in individuals who had bilateral rather than right hemisphere-predominant networks. CONCLUSIONS: The results indicate that the restoration of left-hemisphere language networks is associated with better recovery and inversely related to activity in the compensated or recruited areas of the right hemisphere.

Adult↗

Improved echo volumar imaging (EVI) for functional MRI.

Echo volumar imaging (EVI) is a 3D modification of echo-planar imaging (EPI) that allows data from an entire volume to be acquired following a single RF excitation. EVI provides a high rate of volumar data acquisition, which is advantageous for functional MRI (fMRI). However, few studies to date have applied EVI to fMRI, since because of gradient hardware limitations EVI generally has to be used with long sampling times, resulting in high sensitivity to susceptibility-induced distortions. In this study we modified the EVI sequence to improve its suitability for fMRI. The sampling time is reduced by the use of a high gradient-switching frequency, a small number of echoes, and outer volume suppression (OVS); rewind gradients ameliorate Nyquist ghosting; and phase correction via a calibration scan reduces ghosting and distortion. It is shown that the modified EVI sequence allows fMRI data to be acquired with a temporal resolution of 167 ms.

Brain↗

The effects of anaesthesia on cortical stimulation in rats: a functional MRI study.

The purpose of this study was to investigate the affects of equithesin and isoflurane on cortical activation in the rat using fMRI. Eight healthy male Sprauge-Dawley rats were anaesthetised separately with isoflurane and equithesin following a week in between. Functional EPI images were acquired in axial and sagittal orientations on a Bruker 47/30 Biospec system. Each experiment included repetitive air puffs over the right face region and was divided into 4 OFF (no stimulation) and 3 ON (repeated air puffs) periods. Changes in the BOLD-fMRI signal response were analysed using a box-car response function (SPM99) correlated against each voxel to determine regions of activation (p Corrected <0.0001, Z score>3.54). Neural activation was not detected when equithesin was used except in one rat compared to consistent activation with isoflurane in all 16 functional EPI scans. Equithesin appears to have effectively reduced brain activity in response to sensory stimuli. Isoflurane anaesthesia (1.6%) showed consistent, robust neural activations. It is therefore recommended that equithesin should be further investigated with other functional modalities or behavioural tests prior to consider it as an anaesthetic agent for future functional MRI studies.

Anesthesia↗

Functional MRI and 18F FDG-positron emission tomography for presurgical planning: comparison with electrical cortical stimulation.

BACKGROUND: In patients with mass lesions near "eloquent" cortical areas different preoperative mapping techniques can be used. Two of the most widely used approaches include positron emission tomography (PET) and functional MRI (fMRI). We employed both methods in the same patients undergoing presurgical evaluation and compared the results to those obtained by direct electrical cortical stimulation (DECS). METHOD: 22 patients with tumours of different aetiology near the central region were investigated. FMRI was performed using a T2(*)-weighted gradient-echo BOLD sequence at 1.5 T, PET was performed after injection of 122-301 MBq (18)F-Fluorodeoxyglucose (18-FDG) under rest and activation conditions. DECS was performed in all patients with recordings of muscles primarily involved in the investigated tasks. FINDINGS: In 19 patients all three modalities could be compared, 1 patient demonstrated discordance between fMRI and PET with DECS speaking in favour of fMRI, 6 patients had neighbouring results of PET and fMRI (between 1-2 cm distance), 12 patients had overlapping results. INTERPRETATION: The high incidence of neighbouring results is presumably related to fMRI specific artefacts. Advantages of fMRI are: Higher spatial and temporal resolution, more and different functional runs, shorter examination time, wider availability, longitudinal examinations, non-invasiveness and cost-effectiveness, easy registration to anatomical images. Advantages of PET are: higher signal-to-noise ratio, lesser susceptibility to artefacts (motion, draining veins), evaluation of tumour metabolism. It is our opinion that the neurosurgeon has to decide on a case-by-case basis which study suits his specific needs in the presurgical evaluation of his patient.

Adult↗

New strategy for reconstructing partial-Fourier imaging data in functional MRI.

Most partial Fourier (PF) approaches use a low-resolution phase estimate in the reconstruction to account for non-zero phases of the image. These methods may fail when there are large phase errors, a situation commonly encountered in T(*)(2)-weighted functional MRI (fMRI). To mitigate this problem, a method was developed based on the inversion of a matrix formulated according to a phase map derived from iterative reconstruction. To make this method computationally practical for fMRI, a strategy was introduced such that the matrix inversion is performed only once for each slice in the time series, assuming that the phase map remains constant in the time series. To ensure the temporal phase invariance, physiological noise correction and global phase correction were applied to the data before the reconstruction. This method was demonstrated to be robust and efficient for fMRI. Magn Reson Med 46:1045-1048, 2001.

Algorithms↗

Functional MRI evidence for disparate developmental processes underlying intelligence in boys and girls.

Previous research has shown evidence for sex differences in the neuroanatomical bases for intelligence in adults. Possible differences in the neuroanatomical correlates of intelligence and their developmental trajectories between boys and girls were investigated using functional MRI (fMRI). A large cohort of over 300 children, ages 5-18, performed the semantic processing task of silent verb generation. Regions were found in the left hemisphere exhibiting positive correlations of blood-oxygenation-level-dependent (BOLD) activation with IQ, including the middle temporal gyrus, prefrontal cortex (Broca's area), medial frontal gyrus, precuneus, and cingulate gyrus, while the superior temporal gyrus in the right hemisphere displayed a negative correlation of BOLD activation with IQ. Significant sex-X-IQ and sex-X-IQ-X-age interaction effects were also seen in the left middle temporal gyrus and left inferior frontal gyrus. Using a data-driven analysis procedure, a sex-X-IQ-X-age interaction was also demonstrated in the functional connectivity between regions in the left hemisphere, parameterized as a weighted sum of pairwise covariances between fMRI time courses. While young girls (<13 years) exhibited no correlation of connectivity with intelligence, older girls (>13 years) demonstrated a positive association of functional connectivity with intelligence. Boys, however, demonstrated the opposite developmental trajectory, from a positive association of connectivity with intelligence in young boys (ages <9 years), to a negative association in older boys (ages >13 years). Our results provide evidence for disparate neuroanatomical trajectories underlying intelligence in boys and girls.

Adolescent↗

Functional MRI reveals spatially specific attentional modulation in human primary visual cortex.

Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention.

Attention↗

Functional MRI of the pre-ictal state.

The mechanisms underlying the transition from interictal to ictal states are poorly understood. Non-linear mathematical analysis of EEG frequency components has confirmed the presence of a pre-ictal state in focal epilepsy. We report on functional MRI (fMRI) analysis of the pre-ictal state in three patients with intractable focal epilepsy. Each subject had a typical partial seizure in the scanner while continuous blood oxygen level dependent (BOLD) fMRI images were acquired. The pre-ictal BOLD changes were first analysed by statistically comparing BOLD signals of two one-minute blocks. Further examination of the full time course was then performed. Each patient showed highly significant, focal BOLD signal changes. In Patient 1, a striking pre-ictal BOLD signal increase was seen over the region of the seizure focus identified on complementary epilepsy investigations. No significant BOLD signal decreases were observed. Patient 2 showed widespread pre-ictal BOLD increase contralateral to the presumed seizure focus, as well as a focal BOLD decrease near the presumed seizure focus. In Patient 3, pre-ictal BOLD increase was co-localized with the site of hyperperfusion seen on ictal single photon emission computed tomography (SPECT). However, this was contralateral to the seizure focus localization based on seizure symptomatology. No significant BOLD decreases were seen. The time course data in each patient studied showed change of the BOLD signal several minutes before the onset of the seizure. Highly significant BOLD fMRI signal changes occur before the onset of seizures, supporting the presence of a pre-ictal state. These changes can be localized to the site of the presumed seizure focus, as well as to other brain regions, suggesting that the pre-ictal BOLD signal changes and their underlying mechanisms are complex.

Adolescent↗

Non-invasive assessment of language lateralization by transcranial near infrared optical topography and functional MRI.

Near infrared optical topography (OT) is the simultaneous acquisition of hemoglobin absorption from an array of optical fibers on the scalp to construct maps of cortical activity. We demonstrate that OT can be used to determine lateralization of prefrontal areas to a language task that has been validated by functional MRI (fMRI). Studies were performed on six subjects using a visually presented language task. Laterality was quantified by the relative number of activated pixels in each hemisphere for fMRI, and the total hemoglobin responses in each hemisphere for OT. All subjects showed varying degrees of left hemisphere language dominance and the mean laterality indices for subjects who underwent both OT and fMRI were in good agreement. These studies demonstrate that OT gives predictions of hemispheric dominance that are consistent with fMRI. Due to the ease of use and portable nature of OT, it is anticipated that optical topography will be valuable tool for neurological examinations of cognitive function.

Adult↗

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis.

OBJECTIVE: To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours. METHODS: Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation-that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI. RESULTS: The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy. CONCLUSION: In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

Aged↗

Functional MRI in symptomatic proliferative angiopathies.

Seizures, the main expression of cerebral arteriovenous malformations (AVMs) can be difficult to control medically. We studied fMRI in correlation with clinical findings cerebral activation clusters patterns in relation with singular AVMs (proliferative angiopathy). We carried out blood oxygen-level dependent functional MRI (fMRI) in seven patients with language problems due to capillary ectasia with verbal fluency and repetition language tasks in box-car paradigms. fMRI maps were calculated with cross-correlation coefficients and superimposed on brain anatomy. Five patients had perimalformative and/or contralateral areas of ipsi- and contralateral activation clusters redistribution. One patient who underwent fMRI after a severe focal post-ictal deficit had total hemisphere contralateral activation clusters redistribution.

Adolescent↗

Mechanisms of working memory dysfunction after mild and moderate TBI: evidence from functional MRI and neurogenetics.

Cognitive complaints are a frequent source of distress and disability after mild and moderate traumatic brain injury (TBI). While there are deficits in several cognitive domains, many aspects of these complaints and deficits suggest that problems in working memory (WM) play an important role. Functional imaging studies in healthy individuals have outlined the neural substrate of WM and have shown that regions important in WM circuitry overlap with regions commonly vulnerable to damage in TBI. Use of functional MRI (fMRI) in individuals with mild and moderate TBI suggests that they can have problems in the activation and allocation of WM, and several lines of evidence suggest that subtle alterations in central catecholaminergic sensitivity may underlie these problems. We review the evidence from fMRI and neurogenetic studies that support the role of catecholaminergic dysregulation in the etiology of WM complaints and deficits after mild and moderate TBI.

Brain Injuries↗