Neural activation associated with corrective saccades during tasks with fixation, pursuit and saccades

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-saccade

Alternatives to current disease-modifying treatment in MS: what do we need and what can we expect in the future?

Abstract. : Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are now widely available, and their beneficial effects on relapse rates, magnetic resonance imaging outcomes and, in some cases, relapse-related disability have been shown in numerous clinical studies. However, as these treatments are only partially effective in halting the MS disease process, the search for improved treatment regimens and novel therapies must continue. Strategies to improve our therapeutic armamentarium have to take into account the different phases or parts of the pathogenesis of the disease. Available treatments address systemic immune dysfunction, blood-brain barrier permeability and the inflammatory process in the central nervous system. Currently, patients who fail to respond adequately to first-line DMTs are often considered as candidates for intensive immunosuppression with cytostatic agents or even autologous stem cell transplantation.However, new approaches are being developed. Combination therapies offer an alternative approach that may have considerable potential to improve therapeutic yield and, although likely to present considerable challenges in terms of trial design, this certainly seems to be a logical step forward in view of the complex pathology of MS. Several new drugs are also being developed with the aim of providing more effective, convenient and/or specific modulation of the inflammatory component of the disease. These treatments include humanised monoclonal antibodies such as the anti-VLA-4 antibody natalizumab, inhibitors of intracellular activation, signalling pathways and T-cell proliferation, and oral immunomodulators such as sirolimus, teriflunomide or statins. There remains, however, an urgent need for treatments that protect against demyelination and axonal loss, or promote remyelination/regeneration. Due to the chronicity of MS, the therapeutic window for neuroprotective agents is wider than that following stroke or acute spinal cord injury, and may therefore allow the use of some drugs that have proven disappointing in other situations. Novel potential neuroprotective agents such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonists and ion-channel blockers will be entering Phase II trials in MS in the near future, and it is hoped that these agents will mark the start of a new era for DMTs for M

Effect of fMRI acoustic noise on non-auditory working memory task: comparison between continuous and pulsed sound emitting EPI

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 confoun

MTR variations in normal adult brain structures using balanced steady-state free precession

Introduction: Magnetization transfer (MT) is sensitive to the macromolecular environment of water protons and thereby provides information not obtainable from conventional magnetic resonance imaging (MRI). Compared to standard methods, MT-sensitized balanced steady-state free precession (bSSFP) offers high-resolution images with significantly reduced acquisition times. In this study, high-resolution magnetization transfer ratio (MTR) images from normal appearing brain structures were acquired with bSSFP. Methods: Twelve subjects were studied on a 1.5T scanner. MTR values were calculated from MT images acquired in 3D with 1.3mm isotropic resolution. The complete MT data set was acquired within less than 3.5 min. Forty-one brain structures of the white matter (WM) and gray matter (GM) were identified for each subject. Results: MTR values were higher for WM than GM. In general, MTR values of the WM and GM structures were in good accordance with the literature. However, MTR values showed more homogenous values within WM and GM structures than previous studies. Conclusions: MT-sensitized bSSFP provides isotropic high-resolution MTR images and hereby allows assessment of reliable MTR data in also very small brain structures in clinically feasible acquisition times and is thus a promising sequence for being widely used in the clinical routine. The present normative data can serve as a reference for the future characterization of brain pathologie

Assignment of glial brain tumors in humans by in vivo 1H-magnetic resonance spectroscopy and multidimensional metabolic classification

This study presents a simple approach for the noninvasive assignment of glial brain tumors according to malignancy by single-voxel proteon magnetic resonance spectroscopy at short echo times (TE≦50 milliseconds). Based on peak area ratios, a five-dimensional data set was obtained for each investigated subject. This vector was then projected along metabolic coordinates in a two-dimensional metabolic space. These coordinates had been determined in a previous study (Hagberg G et al., 1995,Magn Reson Med 34: 242-252). Tumor assignment was done without any knowledge of histology by comparing the location of the new cases to the features of the previous study. All 11 investigated glioblastomas multiforme, as well as 4 of 5 astrocytomas grade II, could easily be assigned to the groups of high- and low-grade tumors, respectively. Classification was more difficult in the case of a cystic astrocytoma grade II and one astrocytoma grade III. Two spectra measured in normal-appearing matter of glioblastoma patients were not classified as healthy. Using single-voxel proton magnetic resonance spectroscopy at short echo times with the knowledge of a base study, a straightforward, fast, and noninvasive differential diagnosis of glial brain tumors is possibl

Time-resolved 3D contrast-enhanced MRA with GRAPPA on a 1.5-T system for imaging of craniocervical vascular disease: initial experience

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 1.5s 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 tumor

Non-communicating syringomyelia: a feature of spinal cord involvement in multiple sclerosis

In patients with multiple sclerosis (MS) non-communicating syringomyelia (NCS) has been described as an incidental finding in case studies and small case series. NCS in MS patients commonly leads to uncertainty particularly as the clinical picture of NCS is variable and surgical therapy may be considered. Up to date little is known about the prevalence and clinical importance of NCS in MS. We report the imaging and clinical characteristics of NCS formations in nine MS patients from a 1 year follow-up study in a representative group of 202 MS (4.5%) patients. Brain and spinal cord MRI was performed as part of a genetic study. NCS did commonly extend the central canal and the cord was slightly distended at the level of the syrinx. The cord and syrinx showed no tendency to change in size or shape over 1 year. Despite thorough search into the clinical history and current clinical status no definite but only minimal indications of symptoms potentially related to the NCS were found. We confirm that NCS may occur in MS patients with spinal cord pathology. It can be a subtle finding without clinical correlates. Syrinx formations are more likely to be a consequence of MS cord pathology than a coincidental findin

Head Motion Parameters in fMRI Differ Between Patients with Mild Cognitive Impairment and Alzheimer Disease Versus Elderly Control Subjects

Motion artifacts are a well-known and frequent limitation during neuroimaging workup of cognitive decline. While head motion typically deteriorates image quality, we test the hypothesis that head motion differs systematically between healthy controls (HC), amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) and consequently might contain diagnostic information. This prospective study was approved by the local ethics committee and includes 28 HC (age 71.0±6.9years, 18 females), 15 aMCI (age 67.7±10.9years, 9 females) and 20 AD (age 73.4±6.8years, 10 females). Functional magnetic resonance imaging (fMRI) at 3T included a 9min echo-planar imaging sequence with 180 repetitions. Cumulative average head rotation and translation was estimated based on standard fMRI preprocessing and compared between groups using receiver operating characteristic statistics. Global cumulative head rotation discriminated aMCI from controls [p<0.01, area under curve (AUC) 0.74] and AD from controls (p<0.01, AUC 0.73). The ratio of rotation z versus y discriminated AD from controls (p<0.05, AUC 0.71) and AD from aMCI (p<0.05, AUC of 0.75). Head motion systematically differs between aMCI/AD and controls. Since motion is not random but convoluted with diagnosis, the higher amount of motion in aMCI and AD as compared to controls might be a potential confounding factor for fMRI group comparisons. Additionally, head motion not only deteriorates image quality, yet also contains useful discriminatory information and is available for free as a "side product” of fMRI data preprocessing

Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF

Objective: We investigated the correlation of anti-myelin oligodendrocyte glycoprotein- (anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested, the incidence of more frequent and rapid progression to clinically definite MS (CDMS). Methods: 133 CIS patients were analysed for anti-MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed. 55 patients had a follow-up of at least 12 months or until conversion to CDMS. Results: Patients with anti-MOG and anti-MBP had an increased intrathecal IgG production and CSF white blood cell count (p = 0.048 and p = 0.036). When anti-MBP alone, or both antibodies were present the cranial MRI showed significantly more T2 lesions (p = 0.007 and p = 0.01, respectively). There was a trend for more lesion dissemination in anti-MBP positive patients (p = 0.076). Conversely, anti-MOG- and/or anti-MBP failed to predict conversion to CDMS in our follow-up group (n = 55). Only in female patients with at least one MRI lesion (n = 34) did the presence of anti-MOG correlate with more frequent (p = 0.028) and more rapid (p = 0.0209) transition to CDMS. Conclusions: Presence of anti-MOG or anti-MBP or both was not significantly associated with conversion to CDMS in our CIS cohort. However, patients with anti-MOG and anti-MBP had higher lesion load and more disseminated lesions in cranial MRI as well as higher values for CSF leucocytes and intrathecal IgG production. Our data support a correlation of anti-MOG and anti-MBP to inflammatory signs in MRI and CSF. The prognostic value of these antibodies for CDMS, however, seems to be less pronounced than previously reporte