Parsing a sequence of brain activations at psychological times using fMRI.

Identifying the sequence of computations which constitute a cognitive task is a fundamental problem in neuroscience. Here we show, using functional magnetic resonance imaging (fMRI), that we can parse, at the time scale of about 100 ms, the different stages of brain activations which compose a complex sequential task. To identify timing information from the slow blood oxygen level-dependent (BOLD) signal response, we use a simple analytic method, based on periodic stimulation and an analysis of covariation of the spectral parameters (phase and power spectrum at the stimulation frequency) with the different experimental conditions. We implement this strategy in a sequential task, where the onset and duration of different stages are under experimental control. We are able to detect changes in onset latency and in the duration of the response, in an invariant fashion across different brain regions, and reconstruct the stream of activations consistent with five distinct stages of processing of the task. Sensory and motor clusters activate in the expected order and for the expected duration. The timing of sensory activations is more precise than the timing of motor activation. We also parse in time the reading-verbal network: visual extrastriate and phonological access regions (supramarginal gyrus) activate at the time of word presentation, while the inferior frontal gyrus, the anterior cingulate and the supplementary motor area are activated during the rehearsal period.

Longitudinal thalamic diffusion changes after middle cerebral artery infarcts.

BACKGROUND: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery (MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging (DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans. METHODS: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity (MD), fractional anisotropy (FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls. RESULTS: MD significantly increased in the ipsilateral thalamus between the first and the sixth month (0.766 x 10(-3) mm(2)/s first month; 0.792 x 10(-3) mm(2)/s third month; 0.806 x 10(-3) mm(2)/s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month. CONCLUSION: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings.

Brain anatomy in Turner syndrome: evidence for impaired social and spatial-numerical networks.

Analysis of brain structure in Turner syndrome (TS) provides the opportunity to identify the consequences of the loss of one X chromosome on brain anatomy and to characterize the neural bases underlying the specific cognitive profile of TS subjects which includes deficits in spatial-numerical processing and social cognition. Fourteen subjects with TS and fourteen controls were investigated using voxel-based analysis of high resolution anatomical and diffusion tensor images and using sulcal morphometry. The analysis of anatomical images provided evidence for macroscopical changes in cortical regions involved in social cognition such as the left superior temporal sulcus and orbito-frontal cortex and in a region involved in spatial and numerical cognition such as the right intraparietal sulcus. Diffusion tensor images showed a displacement of the grey-white matter interface of the left and right superior temporal sulcus and revealed bilateral microstructural anomalies in the temporal white matter. The analysis of fiber orientation suggests specific alterations of fiber tracts connecting posterior to anterior temporal regions. Last, sulcal morphometry confirmed the anomalies of the left and right superior temporal sulci and of the right intraparietal sulcus. Our results thus provide converging evidence of regionally specific structural changes in TS that are highly consistent with the hallmark symptoms associated with TS.

Brain imaging of language plasticity in adopted adults: can a second language replace the first?

Do the neural circuits that subserve language acquisition lose plasticity as they become tuned to the maternal language? We tested adult subjects born in Korea and adopted by French families in childhood; they have become fluent in their second language and report no conscious recollection of their native language. In behavioral tests assessing their memory for Korean, we found that they do not perform better than a control group of native French subjects who have never been exposed to Korean. We also used event-related functional magnetic resonance imaging to monitor cortical activations while the Korean adoptees and native French listened to sentences spoken in Korean, French and other, unknown, foreign languages. The adopted subjects did not show any specific activations to Korean stimuli relative to unknown languages. The areas activated more by French stimuli than by foreign stimuli were similar in the Korean adoptees and in the French native subjects, but with relatively larger extents of activation in the latter group. We discuss these data in light of the critical period hypothesis for language acquisition.

Modulation of parietal activation by semantic distance in a number comparison task.

The time to compare two numbers shows additive effects of number notation and of semantic distance, suggesting that the comparison task can be decomposed into distinct stages of identification and semantic processing. Using event-related fMRI and high-density ERPs, we isolated cerebral areas where activation was influenced by input notation (verbal or Arabic notation). The bilateral extrastriate cortices and a left precentral region were more activated during verbal than during Arabic stimulation, while the right fusiform gyrus and a set of bilateral inferoparietal and frontal regions were more activated during Arabic than during verbal stimulation. We also identified areas that were influenced solely by the semantic content of the stimuli (numerical distance between numbers to be compared) independent of the input notation. Activation tightly correlated with numerical distance was observed mainly in a group of parietal areas distributed bilaterally along the intraparietal sulci and in the precuneus, as well as in the left middle temporal gyrus and posterior cingulate. Our results support the assumption of a central semantic representation of numerical quantity that relies on a common parietal network shared among notations.

Diffusion tensor imaging study of subcortical gray matter in cadasil.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown. METHODS: We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images. RESULTS: A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score. CONCLUSIONS: Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.

Human cortical networks for new and familiar sequences of saccades.

Visual exploration is organized in sequences of saccadic eye movements that depend on both perceptual and cognitive context. Using functional magnetic resonance imaging, we studied the neural basis of sequential oculomotor behavior and its dependence on different types of memory by analyzing cerebral activity during performance of newly learned and familiar sequences of eye movements. Compared to a resting condition, both types of sequences activated a common fronto-parietal network, including frontal and supplementary eye fields, and several parietal areas. Within this network, newly learned sequences induced stronger activation than familiar sequences, probably reflecting higher attentional demands. In addition, specific regions were recruited for the performance of new sequences, including pre-supplementary eye fields, the precuneus and the caudate nucleus. This indicates that in addition to attentional modulation, novelty of saccadic sequences requires specific cortical resources, probably related to effortful sequence preparation and coordination as well as to spatial working memory. For familiar sequences, recalled from long-term memory, we observed specific right medial temporo-occipital activation in the vicinity of the boundary between the parahippocampal and lingual gyri, as well as an activation site in the parieto-occipital fissure. We conclude that neuronal resources recruited by the gaze system can change with the familiarity of the scanpath to be executed. This study is important to better understand how the brain implements memorized scanpaths for visual exploration and orienting.

Functional imaging in the work-up of childhood epilepsy.

In children with medically intractable lesional epilepsy, surgery is deemed successful if the epileptogenic focus can be removed while major neurological functions are spared. Current techniques rely on invasive intracranial recordings. The new developments in functional imaging offer the possibility of localizing the epileptogenic focus noninvasively (PET/SPECT) and mapping cognitive functions (fMRI). Ictal SPECT shows hyperperfusion in the focus and has proved to have better localizing value than interictal PET or SPECT, which show focal hypometabolism or hypoperfusion. Ictal SPECT is useful for deciding on the placement of intracranial electrodes in extratemporal epilepsies, particularly in young children. Functional MRI has proved highly accurate for localizing motor and language networks, thus offering the possibilities of replacing the Wada test (language hemispheric lateralization) and studying postlesional brain plasticity. Despite the difficulties of functional imaging in children owing to the limited cooperation that can be expected, ethical constraints, and poor normative data, SPECT/PET and fMRI provide clinically useful information for presurgical work-up of childhood epilepsies.

Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults.

OBJECTIVE: To identify age-dependent activation patterns of verbal fluency with functional MRI (fMRI). BACKGROUND: Few fMRI language studies have been performed in children, and none provide comparison data to adult studies. Normative data are important for interpretation of similar studies in patients with epilepsy. METHODS: A total of 10 normal children (5 boys, 5 girls; mean age, 10.7 years; range, 8.1 to 13.1 years) and 10 normal adults (5 men, 5 women; mean age, 28.7 years; range, 19.3 to 48 years) were studied on a 1.5-T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation to letters. Studies were analyzed with a cross-correlation algorithm (r = 0.7). A region-of-interest analysis was used to determine the extent, magnitude, and laterality of brain activation. RESULTS: Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca's area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% greater extent of activation than adults, with a trend for greater magnitude of activation. Children also had significantly more right hemisphere and inferior frontal gyrus activation than adults. CONCLUSIONS: In a test of verbal fluency, children tended to activate cortex more widely than adults, but activation patterns for fluency appear to be established by middle childhood. Thus, functional MRI using verbal fluency paradigms may be applied to pediatric patient populations for determining language dominance in anterior brain regions. The greater activation found in children, including the right inferior frontal gyrus, may reflect developmental plasticity for the ongoing organization of neural networks, which underlie language capacity.

An anatomical landmark for the supplementary eye fields in human revealed with functional magnetic resonance imaging.

Together with the frontal and parietal eye fields, the supplementary eye field (SEF) is involved in the performance and control of voluntary and reflexive saccades and of ocular pursuit. This region was first described in non-human primates and is rather well localized on the dorsal surface of the medial frontal cortex. In humans the site of the SEF is still ill-defined. Functional imaging techniques have allowed investigation of the location and function of the SEF. However, there is great variability with regard to the published standardized coordinates of this area. We used here the spatial precision of functional magnetic resonance imaging (fMRI) in order to better localize the SEF in individuals. We identified as the SEF a region on the medial wall that was significantly activated when subjects executed self-paced horizontal saccades in darkness as compared to rest. This region appeared to be predominantly activated in the left hemisphere. We found that, despite a discrepancy of >2 cm found in the standardized Talairach coordinates, the location of this SEF-region could be precisely and reliably described by referring to a sulcal landmark found in each individual: the upper part of the paracentral sulcus.

Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study.

Neuropsychological studies have shown that the prefrontal cortex is important in planning and monitoring everyday behaviour. In this study, using functional magnetic resonance imaging (fMRI), we investigated whether specific prefrontal regions are involved in processing a sequence of actions. Subjects were required to perform two different tasks: Script-event order and Sentence-word order. Script sequence and word sequence processing were found to activate partially overlapping areas which are known to be implicated in language processing. In addition, the Script-task activated a large area in the dorsolateral prefrontal cortex (Brodmann area 6 and 8, BA 6 and 8), in both the left and right hemispheres, as well as the left supplementary motor area and left angular gyrus (BA 39). Our results suggest that these prefrontal areas may be more specifically involved in the process of analysing sequential links in the action domain.

Functional lateralization of human gustatory cortex related to handedness disclosed by fMRI study.

Ten healthy subjects aged 20-25 including five right-handed and five left-handed according to the Dellatolas test participated in this functional magnetic resonance imaging (fMRI) study. A 3 Tesla whole-body MR scanner allowed echo planar imaging (EPI)-64 x 64 pixels, repetition time (TR) = 6 s, field of view (FOV) = 20 x 20 cm2--associated to acute anatomical localization of activated foci (256 x 256 pixels). Subjects were bilaterally stimulated with NaCl 85 mM, aspartame 2 mM, quinine hydrochloride 1 mM, glycyrrhizic acid 0.5 mM, guanosine monophosphate 1 mM and D-threonine 250 mM alternating with water. Stimuli and rinse were continuously pushed as bolus of 50 microliters every 3 s to the subject's mouth through microsyringes. We detected brain activated areas by correlation of the MR signal to an on-line perception profile recorded for each experiment and each subject with the finger-span method. We found most activations in the insula and the perisylvian region in agreement with previous electrophysiological studies on monkeys and clinical reports in humans. The superior part of the insula was bilaterally activated, in accordance with a whole-mouth stimulation. A striking lateralization related to handedness was found in a lower part of the insula. This projection in the dominant hemisphere, located in the same coronal plane as the upper insular activation, is the first evidence of a functional lateralization of brain processing involved in taste perception.

Flow-sensitive magnetic resonance imaging in the evaluation of cerebrospinal fluid leaks.

Cerebrospinal fluid (CSF) leaks involving the skull base are associated with considerable morbidity and mortality, and often present a diagnostic challenge. Current diagnostic methods are invasive and cumbersome and involve substantial radiation exposure of the patient. The authors identified seven patients with clinically suspected CSF leaks and evaluated them with a flow-sensitive magnetic resonance imaging (MRI) sequence in addition to more conventional studies. In cases with active CSF leakage, flow characteristics were documented with slow-flow and diffusion-weighted MRI. Unlike current approaches, MRI offers the advantages of rapidity, non-invasiveness, and absence of ionizing radiation. Preliminary results suggest that flow-sensitive MRI may have a role in the evaluation of CSF leaks involving the skull base and temporal bone.

Estimation of the effective self-diffusion tensor from the NMR spin echo.

The diagonal and off-diagonal elements of the effective self-diffusion tensor, Deff, are related to the echo intensity in an NMR spin-echo experiment. This relationship is used to design experiments from which Deff is estimated. This estimate is validated using isotropic and anisotropic media, i.e., water and skeletal muscle. It is shown that significant errors are made in diffusion NMR spectroscopy and imaging of anisotropic skeletal muscle when off-diagonal elements of Deff are ignored, most notably the loss of information needed to determine fiber orientation. Estimation of Deff provides the theoretical basis for a new MRI modality, diffusion tensor imaging, which provides information about tissue microstructure and its physiologic state not contained in scalar quantities such as T1, T2, proton density, or the scalar apparent diffusion constant.

MR diffusion tensor spectroscopy and imaging.

This paper describes a new NMR imaging modality--MR diffusion tensor imaging. It consists of estimating an effective diffusion tensor, Deff, within a voxel, and then displaying useful quantities derived from it. We show how the phenomenon of anisotropic diffusion of water (or metabolites) in anisotropic tissues, measured noninvasively by these NMR methods, is exploited to determine fiber tract orientation and mean particle displacements. Once Deff is estimated from a series of NMR pulsed-gradient, spin-echo experiments, a tissue's three orthotropic axes can be determined. They coincide with the eigenvectors of Deff, while the effective diffusivities along these orthotropic directions are the eigenvalues of Deff. Diffusion ellipsoids, constructed in each voxel from Deff, depict both these orthotropic axes and the mean diffusion distances in these directions. Moreover, the three scalar invariants of Deff, which are independent of the tissue's orientation in the laboratory frame of reference, reveal useful information about molecular mobility reflective of local microstructure and anatomy. Inherently tensors (like Deff) describing transport processes in anisotropic media contain new information within a macroscopic voxel that scalars (such as the apparent diffusivity, proton density, T1, and T2) do not.

MR of diffusion slowing in global cerebral ischemia.

PURPOSE: To investigate the causal connections between ischemia and the hyperintensity in diffusion-weighted MR images that has been associated with it. METHODS: Diffusion-weighted and T2-weighted MR imaging were used in a feline global cerebral ischemia/reperfusion model. Single 30-minute vascular occlusions followed by reperfusion were studied. Global occlusions were used to avoid interpretive complications associated with the temporally unstable hemodynamics of the penumbral zones around focal occlusions and the possible growth of the ischemic and penumbral regions with time. RESULTS: Diffusion-weighted hyperintensity and the associated diffusional slowing were not attributable exclusively to the cessation of blood flow because: 1) it does not appear abruptly at the onset of ischemia; 2) it resolves slowly early in reperfusion; and 3) it reappears after prolonged reperfusion. CONCLUSION: The times during which diffusion-weighted hyperintensity is manifested during ischemia, and recovers with reperfusion, point to a role for energy metabolism failure.

Sacral meningeal cysts: evaluation with MR imaging.

It is often difficult for the radiologist to determine if a given sacral meningeal cyst is causing symptoms. Radiographic criteria for identifying cysts likely to be symptomatic are needed. Using conventional magnetic resonance (MR) imaging along with a specifically designed flow-sensitive sequence, the authors characterized 24 cysts (19 patients) with respect to diameter and communication with the subarachnoid space. They found no significant difference in size between symptomatic and asymptomatic cysts (P > .05) but did observe a clear-cut disparity in the context of communication: Five of five asymptomatic cysts were shown to communicate on MR flow studies, while seven of seven symptomatic cysts were not shown to communicate. The authors propose that flow-sensitive MR imaging is useful in differentiating communicating from noncommunicating sacral meningeal cysts and that this information may be of value in classifying these lesions as more or less likely to be symptomatic.

MR of slow CSF flow in the spine.

PURPOSE: To evaluate a slow-flow MR sequence in normal CSF flow and in CSF flow disturbance in cases of spinal stenosis. METHOD: The method was tested for flow sensitivity and applied to 67 sites of spinal canal compromise. RESULTS: Phantom studies show that flow can be depicted at a velocity of 0.5-1 mm/sec. On clinical images, stagnant CSF is black, flowing CSF is bright. Typically, in high-grade (90%-100%) stenosis, CSF above and below the site of spinal canal compromise (SCC) is black. With intermediate stenosis (50%-89%), CSF above the SCC remains white but becomes black distal to the SCC. Low-grade stenosis shows only localized flow disturbances. CONCLUSION: This easy-to-use sequence can solidify the MR diagnosis of high-grade stenosis when a distinct flow pattern is recognized. Flow patterns for intermediate and low-grade stenosis are less reliable.

On the accuracy of noninvasive thermometry using molecular diffusion magnetic resonance imaging.

Temperature measurement using magnetic resonance imaging (MRI) of water self-diffusion is investigated. Diffusion images and derived temperatures are obtained in polyacrylamide gel phantom. The temperatures measured from MRI are compared with those from temperature probes to verify their accuracy. In general, the difference between temperatures determined from MRI diffusion images over 0.3 cm3 regions of interest and from temperature probes were 0.2 degrees C. It is concluded that current MRI technology allows noninvasive temperature tomography that is comparable with invasive thermometry with respect to temperature accuracy, has spatial and time resolutions that would be useful in hyperthermic oncology.

Hyperthermia system combined with a magnetic resonance imaging unit.

Magnetic resonance imaging (MRI) has recently been proposed as a method to monitor, noninvasively, temperature, blood flow, and cell metabolism during oncologic hyperthermia (HT). To heat and "image" simultaneously, it is necessary to combine a HT device and a MRI unit. As a demonstrative example of the problems associated with implementing such a system, a mini-annular phased array hyperthermia applicator was combined with a 0.5-T whole body MRI unit. With the aid of filters, baluns, and switches, the HT applicator and the MRI unit were made compatible. The overall system was tested using a muscle-equivalent, cylindrically shaped polyacrylamide gel phantom. No interference between the HT device and the MRI unit was observed. Noninvasive temperature images, with a resolution better than 1 degree C/cm, were obtained from images of molecular diffusion recorded before and during heating.