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Combining fMRI and MEG increases the reliability of presurgical language localization: a clinical study on the difference between and congruence of both modalities.

To avoid neurological impairment during surgery near language-related eloquent brain areas, we performed presurgical functional brain mapping with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in 172 patients using language tasks. For MEG localizations, we used either a moving equivalent-current dipole fit or a current-density reconstruction using a minimum variance beamformer with a spatial filter algorithm. We localized the Wernicke and Broca language areas for every patient. We integrated the results into a frameless stereotaxy system. To visualize the results in the navigation microscope during surgery, we superimposed the fMRI and MEG findings on the brain surface. MEG and fMRI results differed in 4% of cases, and in 19%, one modality showed activation but not the other. In the vicinity of large gliomas, the BOLD (blood oxygenation level-dependent) effect was suppressed in 53% of our patients. Of the 124 patients who had surgery, only 7 patients (5.6%) experienced a transient language deterioration, which resolved in all cases. We used MEG and fMRI to show different aspects of brain activity and to establish validation between MEG and fMRI. We conclude that measurement by both MEG and fMRI increases the degree of reliability of language area localization and that the combination of fMRI and MEG is useful for presurgical localization of language-related eloquent cortex.

Brain↗

Differences in superficial and deep source contributions to middle latency auditory evoked potential Pa component in normal subjects and patients with neurologic disease.

Multichannel brain-mapped middle latency auditory evoked potential (MLAEP) data obtained from 15 normal subjects and three neurologically impaired subjects using the common average reference (CAR) were converted off-line to source current density (SCD). This technique is sensitive to activity generated in the superficial cerebral cortex. The SCD maps were subtracted from the CAR maps (CAR-SD). The derived CAR-SD maps are believed to represent the proportion of scalp-recorded activity that is generated deep to the cerebral cortex. Topographic analysis of this data manipulation technique supports the hypothesis that Pa originated from within the temporal lobes bilaterally as well as from a deeper subcortical system.

Adult↗

Dissociated expressive and receptive language functions on magnetoencephalography, functional magnetic resonance imaging, and amobarbital studies. Case report and review of the literature.

Dissociated language functions are largely invalidated by standard techniques such as the amobarbital test and cortical stimulation. Language studies in which magnetoencephalography (MEG) and functional magnetic resonance (fMR) imaging are used to record data while the patient performs lexicosemantic tasks have enabled researchers to perform independent brain mapping for temporal and frontal language functions (MEG is used for temporal and fMR imaging for frontal functions). In this case report, the authors describe a right-handed patient in whom a right-sided insular glioma was diagnosed. The patient had a right-lateralized receptive language area, but expressive language function was identified in the left hemisphere on fMR imaging- and MEG-based mapping. Examinations were performed in 20 right-handed patients with low-grade gliomas (control group) for careful comparison with and interpretation of this patient's results. In these tests, all patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMR imaging, and to categorize as abstract or concrete a set of visually presented words consisting of three Japanese letters for fMR imaging and MEG. The most prominent display of fMR imaging activation by the verb-generation task was observed in the left inferior and middle frontal gyri in all participants, including the patient presented here. Estimated dipoles identified with the abstract/concrete categorization task were concentrated in the superior temporal and supramarginal gyri in the left hemisphere in all control patients. In this patient, however, the right superior temporal region demonstrated significantly stronger activations on MEG and fMR imaging with the abstract/concrete categorization task. Suspected dissociation of the language functions was successfully mapped with these two imaging modalities and was validated by the modified amobarbital test and the postoperative neurological status. The authors describe detailed functional profiles obtained in this patient and review the cases of four previously described patients in whom dissociated language functions were found.

Adult↗

[New development of surgical treatment for malignant brain tumors].

The most important prognosticator for malignant brain tumor patients is the degree of tumor removal. On the other hand, surgical removal should not induce aggravation of the patient performance status. In accordance with the result, surgical planning for glioma should be carefully considered. However, there is no standard guide for preoperative planning to date. However, there is no standard guide for preoperative planning to the present. We attempted to divide gliomas into 5 stages according to the difficulty of the surgery and analyzed the relation between the removal rate and each stage. The results demonstrated that the stage is correlated with the removal rate. This staging might contribute to standardization of glioma surgery. For surgical planning of tumors around the motor area, fiber tractography and magnetoencephalography should be very useful. As an intraoperative examination, monitoring of motor evoked potential is necessary to resect tumors around the motor area. For resection of tumors around the speech area, functional brain mapping under awake surgery is the most reliable method. In addition to these techniques for safe surgery, neuro-navigation and chemical navigation using 5-aminolevulinic acid are used to achieve of the maximum removal rate. Finally, development of preoperative examinations, microsurgical technique, and intraoperative monitoring enabled us to do safer and move sure surgery.

Astrocytoma↗

On the nature of the BOLD fMRI contrast mechanism.

Since its development about 15 years ago, functional magnetic resonance imaging (fMRI) has become the leading research tool for mapping brain activity. The technique works by detecting the levels of oxygen in the blood, point by point, throughout the brain. In other words, it relies on a surrogate signal, resulting from changes in oxygenation, blood volume and flow, and does not directly measure neural activity. Although a relationship between changes in brain activity and blood flow has long been speculated, indirectly examined and suggested and surely anticipated and expected, the neural basis of the fMRI signal was only recently demonstrated directly in experiments using combined imaging and intracortical recordings. In the present paper, we discuss the results obtained from such combined experiments. We also discuss our current knowledge of the extracellularly measured signals of the neural processes that they represent and of the structural and functional neurovascular coupling, which links such processes with the hemodynamic changes that offer the surrogate signal that we use to map brain activity. We conclude by considering applications of invasive MRI, including injections of paramagnetic tracers for the study of connectivity in the living animal and simultaneous imaging and electrical microstimulation.

Animals↗

Correlation of sensorimotor activation with functional magnetic resonance imaging and magnetoencephalography in presurgical functional imaging: a spatial analysis.

In this study we investigated the spatial heterotopy of MEG and fMRI localizations after sensory and motor stimulation tasks. Both methods are frequently used to study the topology of the primary and secondary motor cortex, as well as a tool for presurgical brain mapping. fMRI was performed with a 1.5T MR system, using echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI activation was determined with a cross-correlation analysis. MEG source localization was performed with a single equivalent current dipole model and a current density localization approach. Distances between MEG and fMRI activation sites were measured within the same anatomical 3-D-MR image set. The central region could be identified by MEG and fMRI in 33 of 34 cases. However, MEG and fMRI localization results showed significantly different activation sites for the motor and sensory task with a distance of 10 and 15 mm, respectively. This reflects the different neurophysiological mechanisms: direct neuronal current flow (MEG) and secondary changes in cerebral blood flow and oxygenation level of activated versus non activated brain structures (fMRI). The result of our study has clinical implications when MEG and fMRI localizations are used for pre- and intraoperative brain mapping. Although both modalities are useful for the estimation of the motor cortex, a single modality may err in the exact topographical labeling of the motor cortex. In some unclear cases a combination of both methods should be used in order to avoid neurological deficits.

Adolescent↗

The present and future of cerebral tumor surgery in children.

Cerebral hemisphere tumors are less common than posterior fossa tumors in children, but are still important among childhood tumors. At the present time, many are low grade and can be treated satisfactorily with modern surgical techniques. These techniques include image-guided surgery in the conventional operating room, brain mapping, and surgery in the intraoperative MRI. Technical sophistication is the chief characteristic of present approaches to cerebral cortical tumors. In the future, surgery for these tumors will require both technical and biological sophistication. Malignant cerebral tumors are invasive and heterogeneous and require new understandings of biology to develop effective treatments. These biological understandings will be added to sophisticated surgical techniques for surgical resection, perhaps with local delivery methods.

Brain Mapping↗

Combined neurophysiological studies in Creutzfeldt-Jakob disease: a case report.

EEG and brain mapping (on basal conditions and after i.v. administration of diazepam) and visual, somatosensory and auditory evoked potentials have been performed on a patient at terminal evolution of CJD. These combined neurophysiologic studies indicated that very important functional impairments of either thalamic-frontal circuits and frontal, parietal and occipital cortex were associated with absent or mild dysfunction of the visual, somatosensory and auditory subcortical pathways. Combined neurophysiologic studies are important to better understand the pathophysiologic mechanisms of neurodegenerative diseases.

Aged↗

Intraoperative electrocorticography during tumor resection: impact on seizure outcome in patients with gangliogliomas.

Gangliogliomas are indolent neoplasms that are often associated with long-standing intractable seizures. The seizure-free outcome following ganglioglioma resection alone (or "lesionectomy") has been generally favorable, ranging in most series from 50% to 65%. Thus, the value of resection of epileptogenic cortex in addition to tumor with regard to seizure outcome has been the subject of controversy. The authors describe a series of 12 patients with frontal or temporal lobe gangliogliomas associated with long-standing intractable seizures. In these patients, intraoperative electrocorticography was used to guide the resection of epileptogenic cortex along with tumor. Functional brain mapping, interictal and ictal monitoring of seizures, as well as thorough neuropsychological assessments were performed prior to resection in all cases. Outcome with regard to seizures, tumor recurrence, and neurological deficits was assessed with a mean follow-up period of 3.1 years. There was universal freedom from seizures postoperatively in 11 patients in whom complete or near-complete resection of epileptogenic cortex was achieved. In one patient in whom complete tumor resection and subtotal removal of epileptogenic cortex was achieved, a 95% reduction in seizure frequency was identified. No tumor recurrence or neurological deficits were observed. In a subset of four patients, neuropsychological and cognitive function were evaluated pre- and postoperatively. In these four, a clear trend toward improvement was noted in most functions. Thus, resection of epileptogenic cortex along with tumor may improve seizure outcome in selected patients with tumor-associated epilepsy without engendering identifiable neurological or cognitive deficits attributable to the incremental resection.

Adolescent↗

Writing-specific sites in frontal areas: a cortical stimulation study.

OBJECT: The aim of this study was to determine whether cortical areas involved in the writing process are associated with reading or naming areas in patients undergoing surgery for brain tumors in frontal areas. This study was undertaken to spare all language areas found in patients during surgery. METHODS: Fourteen patients (eight women and six men [mean age 47 years] of whom 12 were right handed, two left handed, 12 monolingual, and two bilingual) who harbored brain tumors in the left (11 patients) or right (three patients) frontal gyri or in rolandic areas, were tested by direct stimulation by using the awake surgery technique for direct brain mapping. Mapping of the frontal gyri was performed using naming, reading, and writing under dictation tasks in the appropriate language(s). Considerable individual variability in language organization among patients was observed. Interferences in writing were found during direct stimulation in the frontal gyri, in cortical sites common or not common to interferences in naming or reading. In dominant regions, patterns of writing dysfunctions were variable and included writing arrest, illegible script, letter omissions, and paragraphia. These dysfunctions were nonspecific (stimulation-induced eye movements) in nondominant frontal regions and in rolandic gyri (hand contractions). In the same patient, different writing impairments could sometimes be observed during stimulation of different sites. As is the case for naming or reading interference sites, writing interference sites could be extremely localized (1 cm2 in diameter). In this group of patients, writing interference sites found in Broca areas were associated with other sites of language interference, whereas writing-specific interference sites were found twice in the dominant middle frontal gyrus. CONCLUSIONS: In this series, we found that writing interference sites could be detected by direct cortical stimulation in dominant inferior and middle frontal gyri regardless of whether they were associated with naming or reading interference sites. Writing disorders elicited by direct stimulation in the frontal lobes are varied and probably depend on the functional status of the stimulated cortical area.

Adolescent↗

Frameless stereotaxy without rigid pin fixation during awake craniotomies.

OBJECTIVE: The accuracy and precision of resection with awake brain mapping is augmented when combined with frameless stereotaxy. Frameless stereotactic assisted surgery, however, typically involves immobilization in Mayfield pins. Rigid fixation, however, may be problematic for individuals undergoing awake craniotomy. We describe an alternate method of frameless stereotaxy without the use of pin fixation. METHODS: The MRI fiducials are placed in proximity to the proposed incision and prepared and draped in the operative field. After craniotomy, the epidural skull clamp (standardly used to support the electrode holder during corticography) is attached. Using the Stealth Navigational System, a spinal reference arc is then clamped onto the skull clamp base. After the fiducials and arc are registered, the probe is used for frameless guidance. RESULTS: In 14 of 15 cases (93%), this technique was successful. One case failed because of close proximity of the fiducials to the incision. The accuracy of the 14 successful cases was less than 4 mm. The error within the lesion itself was always less than 2 mm. Overall, these results are comparable to those achieved using a Mayfield head holder. In all tumor cases, postoperative imaging concurred with intraoperative assessment of a total versus subtotal resection. CONCLUSIONS: By affixing the spinal arc to the skull, the complications and discomfort associated with pin fixation are avoided completely. The patient is free to move without affecting the accuracy. The spine arc, in combination with the skull clamp, provides an efficient, well-tolerated, and accurate method of frameless navigation for the awake patient undergoing craniotomy.

Awareness↗

Projection of topographic maps from curved brain surfaces into a plane.

The environment is represented in the brain by topographic maps. These maps and their interrelationship form a dominant feature in the brain, but unfortunately, they are often projected onto surfaces which are variously curved. It would be useful to be able to compare the topography on these surfaces quantitatively with the origin of the map. This comparison would be possible if the curved brain surfaces could be represented in planes. Therefore, it was necessary to develop a procedure for unfolding maps on convex structures like the retina and the optic tectum of the chick. For this purpose a unit sphere was constructed whose origin was close to the centre of gravity of the curved brain structure. The surface of this structure was then projected into the sphere. From its representation on the spherical surface it was unfolded into the plane using a polar azimuthal radially equidistant projection. Our method can safely be applied to convex structures only. However, it is not limited to the visual system. The mathematical procedure is formulated in such a way as to be easily implemented. It is exemplified by experiments on the optic tectum and the developing retina of the chick.

Animals↗

Mapping of brain sites sensitive to the antidipsogenic effect of tachykinins.

The present study investigated the sensitivity of 12 forebrain and midbrain structures to the antidipsogenic effect of eledoisin, physalaemin and substance P on angiotensin-induced drinking. The three tachykinins elicited the most potent effects when injected into the nucleus preopticus medialis, the nucleus anterior hypothalami and the subfornical organ. In other sites (nuclei lateralis, ventromedialis and posterior hypothalami, nucleus septi lateralis, nucleus interpeduncularis and substantia grisea periventricularis) the effect was lower, and most of these sites showed different sensitivity to the three tachykinins. Finally, the nucleus septi medialis, the nucleus preopticus lateralis and the substantia nigra were refractory to the three tachykinins. These results show that: (1) the antidipsogenic effect of tachykinins can be elicited not only in forebrain, but also in midbrain structures such as the substantia grisea periventricularis and the nucleus interpeduncularis; (2) the distribution of brain sites sensitive to the antidipsogenic effect of substance P and physalaemin is always overlapping, while this is not true for eledoisin. This probably reflects selective distribution and/or activation of distinct subtypes of tachykinin receptors.

Angiotensin II↗

Discrete mapping of brain Mu and delta opioid receptors using selective peptides: quantitative autoradiography, species differences and comparison with kappa receptors.

The opioid peptides, [3H]DAGO and [3H]DPDPE, bound to rat and guinea pig brain homogenates with a high, nanomolar affinity and to a high density of mu and delta receptors, respectively. [3H]DAGO binding to mu receptors was competitively inhibited by unlabelled opioids with the following rank order of potency: DAGO greater than morphine greater than DADLE greater than naloxone greater than etorphine much greater than U50488 much greater than DPDPE. In contrast, [3H]DPDPE binding to delta receptors was inhibited by compounds with the following rank order of potency: DPDPE greater than DADLE greater than etorphine greater than dynorphin(1-8) greater than naloxone much greater than U50488 much greater than DAGO. These profiles were consistent with specific labelling of the mu and delta opioid receptors, respectively. In vitro autoradiographic techniques coupled with computer-assisted image analyses revealed a discrete but differential anatomical localization of mu and delta receptors in the rat and guinea pig brain. In general, mu and delta receptor density in the rat exceeded that in the guinea pig brain and differed markedly from that of kappa receptors in these species. However, while mu receptors were distributed throughout the brain with "hotspots" in the fore-, mid- and hindbrain of the two rodents, the delta sites were relatively diffusely distributed, and were mainly concentrated in the forebrain with particularly high levels within the olfactory bulb (OB), n. accumbens and striatum. Notable regions of high density of mu receptors in the rat and guinea pig brain were the accessory olfactory bulb, striatal "patches" and "streaks," amygdaloid nuclei, ventral hippocampal subiculum and dentate gyrus, numerous thalamic nuclei, geniculate bodies, central grey, superior and inferior colliculi, solitary and pontine nuclei and s. nigra. Tissues of high delta receptor concentration included, OB (external plexiform layer), striatum, n. accumbens, amygdala and cortex (layers I-II and V-VI). Delta receptors in the guinea pig were, in general, similarly distributed to the rat, but in contrast to the latter, the hindbrain regions such as the thalamus, geniculate bodies, central grey and superior and inferior colliculi of the guinea pig were apparently more enriched than the rat. These patterns of mu and delta site distribution differed dramatically from that of the kappa opioid sites in these species studied with the peptide [125I]dynorphin(1-8).

Animals↗

Synthesis and characterization of EADAM: a selective radioligand for mapping the brain serotonin transporters by positron emission tomography.

[11C]N,N-Dimethyl-2-(2'-amino-4'-ethylphenylthio)benzylamine ([11C]EADAM) was synthesized in the development of a serotonin transporter (SERT) imaging ligand for positron emission tomography (PET). The methods of ligand synthesis, results of in vitro characterization, 11C labeling and in vivo micro-PET imaging studies of [11C]EADAM in cynomolgus monkey brain are described. 11C was introduced into N,N-dimethyl-2-(2'-amino-4'-ethylphenylthio)benzylamine (5) by alkylation of N-methyl-2-(2'-amino-4'-ethylphenylthio)benzylamine (10) in 32% radiochemical yield (end of bombardment [EOB], decay-corrected from [11C]methyl iodide). Competition binding assays in cells stably expressing the transfected human dopamine transporter (DAT), SERT and norepinephrine transporter (NET) labeled with [3H]WIN 35428 or [(125)I]RTI-55, [3H]citalopram and [3H]nisoxetine, respectively, indicated the following order of SERT affinity: ADAM>EADAM>>fluvoxamine. The affinity of EADAM for DAT and NET was 500- and >1000-fold lower, respectively, than for SERT. Micro-PET brain imaging studies in a cynomolgus monkey demonstrated high [11C]EADAM uptake in the striatum, thalamus and brainstem. [11C]EADAM uptake in these brain regions peaked in less than 60 min following administration of [11C]EADAM. The tissue-to-cerebellum ratios of the striatum, thalamus and brainstem were 1.67, 1.71 and 1.63, respectively, at 120 min postinjection of [11C]EADAM. Analysis of monkey arterial plasma samples using high-pressure liquid chromatography determined there was no detectable formation of lipophilic radiolabeled metabolites capable of entering the brain. In a displacement experiment with citalopram in a cynomolgus monkey, radioactivity in the striatum, thalamus and brainstem was displaced 20-60 min after administration of citalopram. In a blocking experiment with citalopram in a cynomolgus monkey, radioactivity in the striatum, thalamus and brainstem was significantly reduced. These results support the candidacy of [11C]EADAM as a radioligand for visualizing brain SERT using PET.

Animals↗