Abstract: INTRODUCTION: Diffusion tensor imaging (DTI) techniques demonstrated diffuse bilateral temporal and extra-temporal abnormalities of white matter in patients presenting mesial temporal lobe epilepsy with hippocampal sclerosis (HS). The aim of this study was to assess these diffusion changes following temporal lobe surgery, by applying a novel voxel-based tract-based spatial statistics (TBSS) technique for whole-brain analysis of fractional anisotropy (FA) and mean diffusivity (MD). Second, region-of-interest analysis (ROI) was performed to improve statistical power. MATERIAL AND METHODS: The study included 22 patients with unilateral HS. Twelve patients underwent temporal lobe surgery. Follow up MRI was done in a mean interval of 4 months. Voxelwise pre-operative FA asymmetry in all 22 patients was assessed within subjects between lesional and contralateral hemispheres. The whole-brain post-operative dataset of 10 seizure-free patients was compared with the corresponding pre-operative dataset using voxel-wise statistical analysis. Additionally, regional analysis at the fornices was done with skeleton-based region of interest (SROI). RESULTS: Within a mean interval time of 6.3 months after surgery, 10 of 12 patients were seizure free (83.3%). The voxelwise comparison between lesional and contralateral hemispheres was consistent with previous studies showing a more widespread diffusion alteration in the lesional hemisphere. Voxel-wise comparison between post and pre-operative dataset did not show supra-thresholded voxels. SROI statistical analysis showed significant decrease in FA and increase in MD in the ipsilateral fornix. Significant increase in FA was observed in the contralateral fornix after surgery. CONCLUSION: The ipsi-lesional fornix showed decreased FA and increased MD after surgery, consistent with Wallerian degeneration. In contrast, contra-lesional fornix demonstrated increase in FA. This observation is important for our understanding of the fate of the remaining brain tissue following removal of an epileptic focus. Postoperative increase in FA may reflect structural reorganization in response to epilepsy surgery. The discrepancy between SROI and voxelwise statistics emphasizes the difference of statistical sensitivity between voxelwise and ROI analyses.
Abstract: Background: Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear. Methods: We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI). Results: We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls. Limitations: The major limitation of our study is the small number of patients with bipolar disorder. Conclusion: Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.
Abstract: Elderly individuals display a rapid age-related increase in intraindividual variability (IIV) of their performances. This phenomenon could reflect subtle changes in frontal lobe integrity. However, structural studies in this field are still missing. To address this issue, we computed an IIV index for a simple reaction time (RT) task and performed magnetic resonance imaging (MRI) including voxel based morphometry (VBM) and the tract based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) in 61 adults aged from 22 to 88 years. The age-related IIV increase was associated with decreased fractional anisotropy (FA) as well as increased radial (RD) and mean (MD) diffusion in the main white matter (WM) fiber tracts. In contrast, axial diffusion (AD) and grey matter (GM) densities did not show any significant correlation with IIV. In multivariate models, only FA has an age-independent effect on IIV. These results revealed that WM but not GM changes partly mediated the age-related increase of IIV. They also revealed that the association between WM and IIV could not be only attributed to the damage of frontal lobe circuits but concerned the majority of interhemispheric and intrahemispheric corticocortical connections.
Abstract: The majority of advanced neuroimaging studies implement group level analyses contrasting a group of patients versus a group of controls, or two groups of patients. Such analyses may identify for example changes in grey matter in specific regions associated with a given disease. Although such group investigations provided key contributions to the understanding of the pathological process surrounding a wide range of diseases, they are of limited utility at an individual level. Recently, there is a trend towards individual classification analyses, representing a fundamental shift of the research paradigm. In contrast to group comparisons, these latter studies do not provide insights on vulnerable brain areas but may allow for an early (and ideally preclinical) identification of at risk individuals in routine clinical setting. One currently very popular method in this domain are support vector machines (SVM), yet this method is only one of many available methods in the field of individual classification analyses. The current manuscript reviews the fundamental properties and features of such individual level classification analyses in neurodegenerative diseases.
Abstract: Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI), a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease.
Abstract: OBJECTIVES: Tinnitus consists of a more or less constant aversive tone or noise and is associated with excess auditory activation. Transient distortion of this activation (repetitive transcranial magnetic stimulation, rTMS) may improve tinnitus. Recently proposed operant training in real-time functional magnetic resonance imaging (rtfMRI) neurofeedback allows voluntary modification of specific circumscribed neuronal activations. Combining these observations, we investigated whether patients suffering from tinnitus can (1) learn to voluntarily reduce activation of the auditory system by rtfMRI neurofeedback and whether (2) successful learning improves tinnitus symptoms. METHODS: Six participants with chronic tinnitus were included. First, location of the individual auditory cortex was determined in a standard fMRI auditory block-design localizer. Then, participants were trained to voluntarily reduce the auditory activation (rtfMRI) with visual biofeedback of the current auditory activation. RESULTS: Auditory activation significantly decreased after rtfMRI neurofeedback. This reduced the subjective tinnitus in two of six participants. CONCLUSION: These preliminary results suggest that tinnitus patients learn to voluntarily reduce spatially specific auditory activations by rtfMRI neurofeedback and that this may reduce tinnitus symptoms. Optimized training protocols (frequency, duration, etc.) may further improve the results.
Abstract: Although cross-sectional diffusion tensor imaging (DTI) studies revealed significant white matter changes in mild cognitive impairment (MCI), the utility of this technique in predicting further cognitive decline is debated. Thirty-five healthy controls (HC) and 67 MCI subjects with DTI baseline data were neuropsychologically assessed at one year. Among them, there were 40 stable (sMCI; 9 single domain amnestic, 7 single domain frontal, 24 multiple domain) and 27 were progressive (pMCI; 7 single domain amnestic, 4 single domain frontal, 16 multiple domain). Fractional anisotropy (FA) and longitudinal, radial, and mean diffusivity were measured using Tract-Based Spatial Statistics. Statistics included group comparisons and individual classification of MCI cases using support vector machines (SVM). FA was significantly higher in HC compared to MCI in a distributed network including the ventral part of the corpus callosum, right temporal and frontal pathways. There were no significant group-level differences between sMCI versus pMCI or between MCI subtypes after correction for multiple comparisons. However, SVM analysis allowed for an individual classification with accuracies up to 91.4% (HC versus MCI) and 98.4% (sMCI versus pMCI). When considering the MCI subgroups separately, the minimum SVM classification accuracy for stable versus progressive cognitive decline was 97.5% in the multiple domain MCI group. SVM analysis of DTI data provided highly accurate individual classification of stable versus progressive MCI regardless of MCI subtype, indicating that this method may become an easily applicable tool for early individual detection of MCI subjects evolving to dementia.
Abstract: The ability to pursue moving objects with the eyes is vital to humans. However, it remains unclear how the brain differentiates visual object motion, smooth pursuit eye movements (SPEM), and eye movement-induced relative motion on the retina and where visual-to-oculomotor transformation takes place. To characterize functional differences of SPEM-processing cortical areas, we simultaneously measured functional magnetic resonance imaging (fMRI) and smooth pursuit to visual, oculomotor, and visuo-oculomotor stimuli varying the quantity of background dots of the stimuli. Resulting activations involved the whole visuo-oculomotor network. They varied among regions depending on the functional tasks and parametric changes of the background. Activation in many SPEM regions increased from 1 to 16 background dots but decreased at 36 dots. This could be an effect of coherent-texture perception. Putative MST area was not influenced by the amount of moving or stationary background dots. It probably participates in visuo-oculomotor transformation. Parts of the posterior parietal cortex seem specifically activated with relative motion between eye and background, but not with motion per se. This could be important for the perception of spatial references.
Abstract: The effect of echoplanar imaging (EPI) acoustic background noise on blood oxygenation level dependent (BOLD) activations was investigated. Two EPI pulse sequences were compared: (i) conventional EPI with a pulsating sound component of typically 8-10 Hz, which is a potent physiological stimulus, and (ii) the more recently developed continuous-sound EPI, which is perceived as less distractive despite equivalent peak sound pressure levels. Sixteen healthy subjects performed an established demanding visual n-back working memory task. Using an exploratory data analysis technique (tensorial probabilistic independent component analysis; tensor-PICA), we studied the inter-session/within-subject response variability introduced by continuous-sound versus conventional EPI acoustic background noise in addition to temporal and spatial signal characteristics. The analysis revealed a task-related component associated with the established higher-level working memory and motor feedback response network, which exhibited a significant 19% increase in its average effect size for the continuous-sound as opposed to conventional EPI. Stimulus-related lower-level activations, such as primary visual areas, were not modified. EPI acoustic background noise influences much more than the auditory system per se. This analysis provides additional evidence for an enhancement of task-related, extra-auditory BOLD activations by continuous-sound EPI due to less distractive acoustic background gradient noise.
Abstract: We investigated the neuronal processing of the physiologically particularly important precision grip (opposition of index finger and thumb) by the combination of functional magnetic resonance imaging (fMRI) and an MR-compatible haptic interface. Ten healthy subjects performed isometric precision grip force generation with visual task instruction and real-time visual feedback in a block design. In a 2 x 2 two-factorial design, both the timing and force could be either constant or varying (identical average timing and force). As we expected only small changes in the fMRI response for the different fine-graded motor control conditions, we maximized the sensitivity of the data analysis and implemented a volumes of interest (VOI) restricted general linear model analysis including non-explanatory force regressors to eliminate directly force-related low-level activations. The VOIs were defined based on previous studies. We found significant associations: timing variation (variable vs. constant) and primary motor area (M1) and dorsal premotor area (PMd); force variation (variable vs. constant) and primary somatosensory area (S1), anterior intraparietal area (AIP) and PMd; interaction of timing and force and supplementary motor area (SMA) and AIP. We conclude that SMA and AIP integrate fine-graded higher-level timing and force control during precision grip. M1, S1 and PMd process lower-level timing and force control, yet not their integration. These results are the basis for a detailed assessment of manual motor control in a variety of motor diseases. The detailed behavioural assessment by our MR-compatible haptic interface is particularly valuable in patients due to expected larger inter-individual variation in motor performance.
Abstract: Again and again, attempts have been made to find correlates of sex/gender differences in the human brain. Despite the insistence with which differences have been stated, empirical results have not been unequivocal: evidence for and against the influence of sex in the makeup of men's and women's brains has been presented. This article focuses on the relevance of sex/gender related differences in fMRI research, especially with regard to language processing. By discussing some crucial criteria from fMRI examinations, we demonstrate the existence of paradigmatic, methodological and statistical defaults that interfere with assessing the presence or absence of sex/gender differences. These criteria are, among others, the use of contrast analyses, the function of the variable sex/gender as a co-item and the "publication bias". It is argued that dealing with the sex/gender variable will, at least to some degree, inevitably lead to the detection of differences rather than to the detection of similarities.
Abstract: PURPOSE: To investigate whether cortical thickness analysis in individuals with an at-risk mental state (ARMS) might contribute to early detection of psychosis. MATERIALS AND METHODS: Ethics committee approval and written informed consent were obtained. Cortical thickness was analyzed because early disease-related morphometric changes were expected to be most pronounced in the cerebral cortex. With the assumption of progressive change in cortical thickness from control subjects, to those with an ARMS, and then to those who have had a first episode (FE) of psychosis, the brain regions that substantially differ between those with FE psychosis and control subjects were identified. Whether these regions help discriminate between the ARMS group and control subjects was tested. Because normal interindividual variation of cortical thickness, even for control subjects, may exceed that expected with early disease-related changes, intraindividual cortical thickness asymmetry was analyzed. Twenty age- and sex-matched individuals for each group (ARMS group, FE group, and control subjects) were recruited within a prospective early-detection study. High-spatial-resolution magnetization-prepared rapid gradient-echo magnetic resonance (MR) brain images were acquired with a 1.5-T MR imager. Cortical thickness asymmetry was analyzed in 41 anatomic regions corresponding to the Talairach standard brain atlas. RESULTS: Direct cortical thickness analysis did not help distinguish between groups. Cortical thickness asymmetry analysis helped distinguish between groups (P = .007); variability increased from control subjects, to the ARMS group, and then to the FE group in seven anatomic regions (P < .0001). Cortical thickness asymmetry in these regions helped distinguish the FE group from control subjects (P = .0006; sensitivity, 70.0%; specificity, 85.0%) and showed a trend toward helping to distinguish the ARMS group from control subjects (P = .06; sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: Cortical thickness asymmetry analysis is more accurate than direct cortical thickness measurement in distinguishing the control from the FE group and might contribute to early detection of an ARMS.
Abstract: It is generally accepted that the presence of a second language (L2) has an impact on the neuronal substrates build up and used for language processing; the influence of the age of L2 exposure, however, is not established. We tested the hypothesis that the age of L2 acquisition has an effect on the cortical representation of a multilingual repertoire in 44 multilinguals with different age of exposure to a L2 (simultaneous or covert simultaneous exposure to L1 and L2, sequential acquisition of L1 and L2 between 1 and 5 years, late learning of L2 after 9 years of age) and all fluent in a late learned L3. Regional activation in a language production task showed a high in-between-subject variability, which was higher than within-subject variability between L1, L2, and L3. We, therefore, performed a single subject analysis and calculated the within-subject variance in the numbers of activated voxels in Broca's and Wernicke's area. Subjects with early exposure to L2 showed low variability in brain activation in all three languages, in the two early as well as the late learned language. In contrast, late multilinguals exhibited higher variability. Thus, cerebral representation of languages is linked to the age of L2 acquisition: early exposure to more than one language gives rise to a language processing network that is activated homogeneously by early and late learned languages, while the inhomogeneous activation in late multilinguals indicates more independent access to the multilingual repertoire. Early passive exposure to L2 results in the same low variance as active bilingual upbringing. Variability in local brain activity increases progressively from the simultaneous to late L2 exposure, indicating a gradual transition from the mode of early bilingual language representation to that of late ones.
Abstract: Metabolic diseases of the brain are a rare occurrence. They may be either occurring as inherited diseases causing a destruction of myelin, or they may be the result of toxicity. Neuroimaging, especially magnetic resonance imaging, plays an important role in the detection and classification of these rare diseases. Magnetic resonance spectroscopy is an important tool in the characterization and diagnosis of inherited metabolic diseases.
Abstract: excellent soft tissue contrast, noninvasiveness, assessment of multiple structural and functional parameters, and absence of radiation are the essential properties of magnetic resonance imaging explaining why this modality is the technique of choice for the assessment of cerebral white matter (WM).
Abstract: multiple sclerosis (MS) is an inflammatory disease of unknown origin affecting the central nervous system. Magnetic resonance imaging (MRI) plays an increasingly important role in its diagnosis and further monitoring of disease progress.
Abstract: Infections of the nervous system are a common and serious occurrence. Neuroimaging has allowed to improve early detection and thus to initiate treatment earlier. Magnetic resonance (MR) imaging has become the method of choice in investigating a patient with suspicion of an infection of the central nervous system. Newer modalities such as MR spectroscopy and MR diffusion and perfusion will further help to improve diagnostic accuracy of the technique. For the investigation of infections of white matter, techniques such as diffusion imaging are essential.
Abstract: Several different techniques allow a functional assessment of neuronal activations by magnetic resonance imaging (fMRI). The by far most influential fMRI technique is based on a local T2*-sensitive hemodynamic response to neuronal activation, also known as the blood oxygenation level dependent or BOLD effect. Consequently, the term 'fMRI' is often used synonymously with BOLD imaging. Because interpretations of fMRI brain activation maps often appear intuitive and compelling, the reader might be tempted not to critically question the fundamental processes and assumptions. We review some essential processes and assumptions of BOLD fMRI and discuss related confounds and pitfalls in fMRI - from the underlying physiological effect, to data acquisition, data analysis and the interpretation of the results including clinical fMRI. A background framework is provided for the systematic and critical interpretation of fMRI results.
Abstract: Magnetic resonance imaging plays an important role in the diagnosis and management of cerebrovascular diseases. In addition to stroke, it can also demonstrate changes apparent in the white matter such as leukoaraiosis. These as well as other changes occurring with increasing age can be visualized. Among others, there is an increase in the number and size of perivascular spaces. Although many of these alterations may be clinically silent, with increasing load they may become symptomatic. Other vascular pathological findings such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the posterior reversible encephalopathy syndrome can also provoke changes in the cerebral white matter that are visible on magnetic resonance imaging and are discussed.
Abstract: Motion stimuli in one visual hemifield activate human primary visual areas of the contralateral side, but suppress activity of the corresponding ipsilateral regions. While hemifield motion is rare in everyday life, motion in both hemifields occurs regularly whenever we move. Consequently, during motion primary visual regions should simultaneously receive excitatory and inhibitory inputs. A comparison of primary and higher visual cortex activations induced by bilateral and unilateral motion stimuli is missing up to now. Many motion studies focused on the MT+ complex in the parieto-occipito-temporal cortex. In single human subjects MT+ has been subdivided in area MT, which was activated by motion stimuli in the contralateral visual field, and area MST, which responded to motion in both the contra- and ipsilateral field. In this study we investigated the cortical activation when excitatory and inhibitory inputs interfere with each other in primary visual regions and we present for the first time group results of the MT+ subregions, allowing for comparisons with the group results of other motion processing studies. Using functional magnetic resonance imaging (fMRI), we investigated whole brain activations in a large group of healthy humans by applying optic flow stimuli in and near the visual field centre and performed a second level analysis. Primary visual areas were activated exclusively by motion in the contralateral field but to our surprise not by central flow fields. Inhibitory inputs to primary visual regions appear to cancel simultaneously occurring excitatory inputs during central flow field stimulation. Within MT+ we identified two subregions. Putative area MST (pMST) was activated by ipsi- and contralateral stimulation and located in the anterior part of MT+. The second subregion was located in the more posterior part of MT+ (putative area MT, pMT).
Abstract: INTRODUCTION: Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disease due to a mutation in the ROBO3 gene. This rare disease is of particular interest because the absence, or at least reduction, of crossing of the ascending lemniscal and descending corticospinal tracts in the medulla predicts abnormal ipsilateral sensory and motor systems. METHODS: We evaluated the use of functional magnetic resonance imaging (fMRI) for the first time in this disease and compared it to diffusion tensor imaging (DTI) tractography and neurophysiological findings in the same patient with genetically confirmed ROBO3 mutation. RESULTS: As expected, motor fMRI, somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) were dominantly ipsilateral to the stimulation side. DTI tractography revealed ipsilateral ascending and descending connectivity in the brainstem yet normal interhemispheric connections in the corpus callosum. Auditory fMRI revealed bilateral auditory activation to monaural left-sided auditory stimulation. No significant cortical activation was observed after monaural right-sided stimulation, a hearing defect having been excluded. Prosaccades fMRI showed no activations in the eye-movement network. CONCLUSION: Motor fMRI confirmed the established findings of DTI and neurophysiology in the same patient. In suspected HGPPS, any technique appears appropriate for further investigation. Auditory fMRI suggests that a monaural auditory system with bilateral auditory activations might be a physiological advantage as compared to a binaural yet only unilateral auditory system, in analogy to anisometropic amblyopia. Moving-head fMRI studies in the future might show whether the compensatory head movements instead of normal eye movements activate the eye-movement network.
Abstract: Corrective saccades are small eye movements that redirect gaze whenever the actual eye position differs from the desired eye position. In contrast to various forms of saccades including pro-saccades, recentering-saccades or memory guided saccades, corrective saccades have been widely neglected so far. The fMRI correlates of corrective saccades were studied that spontaneously occurred during fixation, pursuit or saccadic tasks. Eyetracking was performed during the fMRI data acquisition with a fiber-optic device. Using a combined block and event-related design, we isolated the cortical activations associated with visually guided fixation, pursuit or saccadic tasks and compared these to the activation associated with the occurrence of corrective saccades. Neuronal activations in anterior inferior cingulate, bilateral middle and inferior frontal gyri, bilateral insula and cerebellum are most likely specifically associated with corrective saccades. Additionally, overlapping activations with the established pro-saccade and, to a lesser extent, pursuit network were present. The presented results imply that corrective saccades represent a potential systematic confound in eye-movement studies, in particular because the frequency of spontaneously occurring corrective saccades significantly differed between fixation, pursuit and pro-saccades.
Abstract: Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migraine-like headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy.No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.
Abstract: Smooth pursuit eye movements (SP) are driven by moving objects. The pursuit system processes the visual input signals and transforms this information into an oculomotor output signal. Despite the object's movement on the retina and the eyes' movement in the head, we are able to locate the object in space implying coordinate transformations from retinal to head and space coordinates. To test for the visual and oculomotor components of SP and the possible transformation sites, we investigated three experimental conditions: (I) fixation of a stationary target with a second target moving across the retina (visual), (II) pursuit of the moving target with the second target moving in phase (oculomotor), (III) pursuit of the moving target with the second target remaining stationary (visuo-oculomotor). Precise eye movement data were simultaneously measured with the fMRI data. Visual components of activation during SP were located in the motion-sensitive, temporo-parieto-occipital region MT+ and the right posterior parietal cortex (PPC). Motor components comprised more widespread activation in these regions and additional activations in the frontal and supplementary eye fields (FEF, SEF), the cingulate gyrus and precuneus. The combined visuo-oculomotor stimulus revealed additional activation in the putamen. Possible transformation sites were found in MT+ and PPC. The MT+ activation evoked by the motion of a single visual dot was very localized, while the activation of the same single dot motion driving the eye was rather extended across MT+. The eye movement information appeared to be dispersed across the visual map of MT+. This could be interpreted as a transfer of the one-dimensional eye movement information into the two-dimensional visual map. Potentially, the dispersed information could be used to remap MT+ to space coordinates rather than retinal coordinates and to provide the basis for a motor output control. A similar interpretation holds for our results in the PPC region.
Abstract: PURPOSE: To determine whether any initial reductions in cardiovascular reserve (CVR) normalize after carotid revascularization and-because reduced CVR represents a risk factor for ischemic events-whether patients who develop periinterventional infarction have more severely reduced pretreatment CVR than those who do not. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Twenty-four consecutive patients with symptomatic high-grade internal carotid artery stenosis (seven women; mean age, 73.1 years +/- 9.4 [standard deviation]) were recruited from a prospective, randomized trial that compared carotid artery stent placement with endarterectomy. Magnetic resonance (MR) imaging, including CO(2) blood oxygen level-dependent (BOLD) MR, was performed 1-3 days before, 1-3 days after, and 1 month after carotid revascularization (carotid artery stent placement, n = 13; carotid endarterectomy, n = 11). RESULTS: Mean CVR in the ipsilateral middle cerebral artery (MCA) territory was reduced prior to treatment (mean DeltaT2* in ipsilateral territory, 1.92% +/- 1.18; mean DeltaT2* in contralateral territory, 2.28% +/- 1.15 [P < .05]) and normalized after treatment (mean DeltaT2* 1-3 days after treatment in ipsilateral territory, 2.66% +/- 1.01; that in contralateral territory, 2.48% +/- 1.27 [P > .05]; mean DeltaT2* 1 month after treatment in ipsilateral territory, 2.27% +/- 1.05; that in contralateral territory, 2.14% +/- 0.96 [P > .05]). Those patients who developed new periinterventional infarcts (n = 7 with punctate foci of restricted diffusion) had greater reduction of CVR in the ipsilateral MCA territory prior to treatment (relative reduction, 32.5% +/- 46.0; P < .05) than those who did not develop infarction (n = 17; relative reduction, 9.2% +/- 55.9). CONCLUSION: CO(2) BOLD MR imaging could be used successfully to monitor the hemodynamic effects of carotid revascularization; initial reductions in CVR normalized after carotid revascularization. Severely reduced pretreatment CVR was associated with increased occurrence of new periinterventional therapy infarction.
Abstract: Isolation of the pulmonary veins has emerged as a new therapy for atrial fibrillation. Pre-procedural magnetic resonance (MR) imaging enhances safety and efficacy; moreover, it reduces radiation exposure of the patients and interventional team. The purpose of this study was to optimize the MR protocol with respect to image quality and acquisition time. In 31 patients (23-73 years), the anatomy of the pulmonary veins, left atrium and oesophagus was assessed on a 1.5-Tesla scanner with four different sequences: (1) ungated two-dimensional true fast imaging with steady precession (2D-TrueFISP), (2) ECG/breath-gated 3D-TrueFISP, (3) ungated breath-held contrast-enhanced three-dimensional turbo fast low-angle shot (CE-3D-tFLASH), and (4) ECG/breath-gated CE-3D-TrueFISP. Image quality was scored from 1 (structure not visible) to 5 (excellent visibility), and the acquisition time was monitored. The pulmonary veins and left atrium were best visualized with CE-3D-tFLASH (scores 4.50 +/- 0.52 and 4.59 +/- 0.43) and ECG/breath-gated CE-3D-TrueFISP (4.47 +/- 0.49 and 4.63 +/- 0.39). Conspicuity of the oesophagus was optimal with CE-3D-TrueFISP and 2D-TrueFISP (4.59 +/- 0.35 and 4.19 +/- 0.46) but poor with CE-3D-tFLASH (1.03 +/- 0.13) (p < 0.05). Acquisition times were shorter for 2D-TrueFISP (44 +/- 1 s) and CE-3D-tFLASH (345 +/- 113 s) compared with ECG/breath-gated 3D-TrueFISP (634 +/- 197 s) and ECG/breath-gated CE-3D-TrueFISP (636 +/- 230 s) (p < 0.05). In conclusion, an MR imaging protocol comprising CE-3D-tFLASH and 2D-TrueFISP allows assessment of the pulmonary veins, left atrium and oesophagus in less than 7 min and can be recommended for pre-procedural imaging before electric isolation of pulmonary veins.
Abstract: BACKGROUND: Individuals with an At Risk Mental State (ARMS) have a very high risk of developing a psychotic disorder but the basis of this risk is unclear. We addressed this issue by studying gray matter volume in this group with magnetic resonance imaging (MRI). METHODS: Thirty-five individuals with an ARMS, 25 patients with first episode schizophrenia, and 22 healthy volunteers were studied using a 1.5T MRI scanner. Twelve (34%) of the ARMS group developed schizophrenia in the 2 years subsequent to scanning. RESULTS: There were significant volumetric differences between the three groups in the left insula, superior temporal gyrus, cingulate gyrus and precuneus. In these regions, the volume in the ARMS group was smaller than in volunteers but not significantly different from that in the first episode (FE) group. Direct comparison of the ARMS and control groups revealed additional areas of reduced volume in the left medial temporal cortex. Within the ARMS group, those subjects who later developed psychosis had less gray matter than subjects who did not in the right insula, inferior frontal and superior temporal gyrus. CONCLUSIONS: The ARMS was associated with reductions in gray matter volume in areas that are also reduced in schizophrenia, suggesting that these are a correlate of an increased vulnerability to psychosis. Volumetric differences within the ARMS group may be related to the subsequent onset of schizophrenia in a subset of those at high risk.
Abstract: Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.
Abstract: A moving object draws our attention to it and we can track the object with smooth pursuit eye movements (SPEM). Gaze and attention are usually directed to the same object during SPEM. In this study we investigated whether gaze and attention can be divided during pursuit. We explored the cortical control of ocular tracking and attentive tracking and the role of focused and divided attention. We presented a sinusoidally moving target for pursuit and simultaneously a stationary target for fixation. Gaze could be directed to the pursuit target and attention to the fixation target or vice versa, or gaze and attention were directed to the same (moving or stationary) target. We found that gaze (overt) and attentive (covert) pursuit similarly activated the cortical oculomotor network. Gaze pursuit showed higher activations than attentive pursuit. Activations, specific to the dissociation of attention from gaze and independent of eye movements, were found solely in the posterior parietal cortex. A cue indicating a forthcoming attention task activated large parts of the cortical SPEM network, as a kind of preparatory mechanism. We did not find any attention-related regions outside the well-known visuo-oculomotor network. We conclude that attention control during gaze pursuit and gaze fixation occur within the cortical SPEM network, supporting the premotor theory of attention [Rizzolatti, G., Riggio, L., Dascola, I. & Umilta, C. (1987) Neuropsychologia, 25, 31-40].
Abstract: Standard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON-OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation. Compared with standard fMRI, we introduced the application of CO(2) as potent vasodilator. CO(2) induces a 'global' blood oxygenation level-dependent (BOLD) response. The neurovascular coupling in conjunction with the limited cerebral vasodilation implies a limitation or ceiling of the BOLD response. We hypothesize that active areas exhibit a reduced CO(2)-induced DeltaBOLD due to pre-existing 'local' task-induced BOLD response. This putative reduction in DeltaBOLD might be exploited for mapping of continuous neuronal activation. BOLD ceiling fMRI was tested in the auditory system. Six healthy subjects performed three runs: only continuous monaural auditory; only 10% CO(2); simultaneous auditory and CO(2) stimulation. First, we demonstrated the ceiling of DeltaBOLD during continuous auditory activation. According to the known predominantly contralateral auditory processing, monaural auditory stimulation reduced predominantly contralateral (0.41 +/- 0.13%; P < 0.00001) and significantly less (P < 0.0001) ipsilateral DeltaBOLD (0.33 +/- 0.17%; P < 0.00001). The non-auditory area was not affected. Second, this BOLD ceiling was exploited to generate an initial activation map of continuous auditory activation (ON period). In contrast to standard fMRI, an OFF period without neuronal activation was not required. BOLD ceiling fMRI is proposed as a complement to standard fMRI for those conditions where ON-OFF paradigms are impossible.
Abstract: Palatal tremor (PT), also known as palatal myoclonus, is defined by short rhythmic contractions of the palatal musculature. Functional MR imaging (fMRI) revealed prominent bilateral neuronal activation in the putamen associated with essential palatal tremor (EPT) in a 41-year-old man. This implies a central role of the putamen in EPT, most likely as a consequence of diminished inhibition in an afferent pathway. Because fMRI primarily detects activations, dysfunctional areas remain obscure. The present functional study complements previous pathologic studies, which associated PT with lesions to dentate nucleus, red nucleus, and the inferior olive (Guillain-Mollaret triangle).
Abstract: INTRODUCTION: For three-dimensional (3D) imaging with magnetic resonance angiography (MRA) of the cerebral and cervical circulation, both a high temporal and a high spatial resolution with isovolumetric datasets are of interest. In an initial evaluation, we analyzed the potential of contrast-enhanced (CE) time-resolved 3D-MRA as an adjunct for neurovascular MR imaging. METHODS: In ten patients with various cerebrovascular disorders and vascularized tumors in the cervical circulation, high-speed MR acquisition using parallel imaging with the GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) algorithm on a 1.5-T system with a temporal resolution of 1.5 s per dataset and a nearly isovolumetric spatial resolution was applied. The results were assessed and compared with those from conventional MRA and digital subtraction angiography (DSA). RESULTS: CE time-resolved 3D-MRA enabled the visualization and characterization of high-flow arteriovenous shunts in cases of vascular malformations or hypervascularized tumors. In steno-occlusive disease, the method provided valuable additional information about altered vessel perfusion compared to standard MRA techniques such as time-of-flight (TOF) MRA. The use of a nearly isovolumetric voxel size allowed a free-form interrogation of 3D datasets. Its comparatively low spatial resolution was found to be the major limitation. CONCLUSION: In this preliminary analysis, CE time-resolved 3D-MRA was revealed to be a promising complementary MRA sequence that enabled the visualization of contrast flow dynamics in various types of neurovascular disorders and vascularized cervical tumors.
Abstract: OBJECTIVE: To assess the prevalence of radiological magnetic resonance imaging (MRI) findings in individuals at high risk of schizophrenia. METHODS: MRI scans from individuals at high risk of schizophrenia (HR; n = 37) were assessed by a radiologist blind to group status and compared with scans from patients with first episode psychosis (FE; n = 30), depressive controls (DC; n = 17), and healthy controls (HC; n = 26). RESULTS: There was a significantly higher proportion of radiological findings in individuals at high risk of schizophrenia (35%) and patients with first-episode psychosis (40%) than in patients with depression (18%) or healthy controls (12%). These differences were specific to findings regarded as potentially clinically significant as opposed to normal variants; however, there was no indication for medical treatment. CONCLUSIONS: The results suggest that a large proportion of those at high risk of psychosis have radiological findings on MRI scanning, and that the prevalence of radiological findings in this group is similar to that in patients with first episode psychosis.
Abstract: PURPOSE: To investigate neuronal activations during processing of radiologic and nonradiologic images by experienced radiologists and nonradiologist subjects by using event-related functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: Study was approved by local ethics committee, and informed consent was obtained. Radiologic and control images were presented to 12 experienced radiologists (mean age, 35.8 years +/- 3.6 [standard deviation]) and 12 nonradiologist subjects (mean age, 33.0 years +/- 6.9). Half of the images were artificially manipulated-that is, for example, a local shadow was introduced. Subjects had to indicate whether a visually presented image was original or manipulated, while neuronal activity was assessed by using event-related functional MR imaging. Analysis was performed on the basis of fixed-effects general linear models with correction for multiple comparisons (false discovery rate). RESULTS: Radiologic images, when compared with control images, evoked stronger activations exclusively in the group of radiologists, notably in the bilateral middle and inferior temporal gyrus, bilateral medial and middle frontal gyrus, and left superior and inferior frontal gyrus (P < .001, corrected). Additionally, visual processing of control images (ie, nonradiologic images) differed significantly between experienced radiologists and nonradiologist subjects (P < .001, corrected). Radiologists showed strongest activation in the left-dominant more posterior superior and inferior parietal lobule, while nonradiologist subjects showed strongest activation in the right-dominant more anterior superior and inferior parietal lobule and postcentral gyrus. CONCLUSION: With radiologic experience, there is selective enhancement of brain activation with radiologic images, and the visual system is modified in general.
Abstract: Cerebrovascular disease, in particular stroke, is a common complication in cancer patients, secondary in incidence only to brain metastases. Autopsy studies suggest that a substantial proportion of strokes in these patients is overlooked in the clinical setting. In general, the clinical presentation of stroke in cancer patients and in nononcologic patients is similar. Embolic focal cerebral ischemia is the most frequent type of stroke with a reported ratio of approximately 55%, which is substantially lower than the ratio of approximately 80% in the general population. The underlying malignancy influences the proportion of embolic versus hemorrhagic stroke. The most common cause of stroke in cancer patients is nonbacterial thrombotic endocarditis (NBTE), a noninfectious type of endocarditis characterized by sterile fibrin vegetations. Other common causes, in the order of frequency, include tumor-induced coagulopathy, atherosclerosis, modification of blood viscosity, and therapy-induced stroke. There is no general agreement whether cancer is an independent risk factor for stroke such as traditional risk factors like hypertension or smoking. The challenge to the clinician is to elaborate whether the stroke is specifically related to cancer or whether it is due to vascular comorbidity like in the general population. The treatment of stroke in cancer patients is usually similar to the treatment of stroke in the general population, except for the treatment of the underlying malignancy if applicable.
Abstract: The use of syntactic structures on a sentence level is a unique human ability. Functional imaging studies have usually investigated syntax comprehension. However, language production may be performed by different neuronal resources. We have investigated syntax generation on a sentence level with functional magnetic resonance imaging (fMRI). BOLD contrast was measured while subjects articulated utterances aloud. In the active condition 'sentence generation' (SG), subjects had to produce subject verb object (SVO) sentences (e.g. "The child throws the ball") according to syntactically incomplete stimuli (e.g. "throw ball child") presented visually. In the control condition 'word reading' (WR), subjects had to read identical stimuli without completing the syntactic structure, while in a second control condition 'sentence reading' (SR), subjects had to read complete sentences. The semantic meaning of all expressions was obvious despite the syntactically incomplete structure in conditions SG and WR. In both contrasts, SG minus WR and SG minus SR, activation was mainly present in the left inferior frontal (BA 44/45) and medial frontal (BA 6) gyri, the superior parietal lobule (BA 7) and the right insula (BA 13). A region of interest analysis revealed significantly stronger left-dominant activation in BA 45 compared to BA 44. Our data illustrates the crucial involvement of the left BA 45 in syntactic encoding and is in line with more recent imaging and brain lesion data on syntax processing on a sentence level, emphasizing the involvement of a distributed left and right hemispheric network in syntax generation.
Abstract: Conventional blood oxygenation level-dependent (BOLD) based functional magnetic resonance imaging (fMRI) is accompanied by substantial acoustic gradient noise. This noise can influence the performance as well as neuronal activations. Conventional fMRI typically has a pulsed noise component, which is a particularly efficient auditory stimulus. We investigated whether the elimination of this pulsed noise component in a recent modification of continuous-sound fMRI modifies neuronal activations in a cognitively demanding non-auditory working memory task. Sixteen normal subjects performed a letter variant n-back task. Brain activity and psychomotor performance was examined during fMRI with continuous-sound fMRI and conventional fMRI. We found greater BOLD responses in bilateral medial frontal gyrus, left middle frontal gyrus, left middle temporal gyrus, left hippocampus, right superior frontal gyrus, right precuneus and right cingulate gyrus with continuous-sound compared to conventional fMRI. Conversely, BOLD responses were greater in bilateral cingulate gyrus, left middle and superior frontal gyrus and right lingual gyrus with conventional compared to continuous-sound fMRI. There were no differences in psychomotor performance between both scanning protocols. Although behavioral performance was not affected, acoustic gradient noise interferes with neuronal activations in non-auditory cognitive tasks and represents a putative systematic confound.
