Validation of quantitative scores derived from motor evoked potentials in the assessment of primary progressive multiple sclerosis: a longitudinal study

Objective:; To evaluate the sensitivity to change of differently calculated quantitative scores from motor evoked potentials (MEP) in patients with primary progressive multiple sclerosis (PPMS).; Methods:; Twenty patients with PPMS had MEP to upper and lower limbs at baseline, years 1 and 2 measured in addition to clinical assessment [Expanded Disability Status Scale (EDSS), ambulation score]; a subsample (; n; = 9) had a nine-hole peg test (NHPT) and a timed 25-foot walk (T25FW). Quantitative MEP scores for upper limbs (qMEP-UL), lower limbs (qMEP-LL), and all limbs (qMEP) were calculated in three different ways, based on; z; -transformed central motor conduction time (CMCT), shortest corticomuscular latency (CxM-sh), and mean CxM (CxM-mn). Changes in clinical measures and qMEP metrics were analyzed by repeated-measures analysis of variance (rANOVA), and a factor analysis was performed on change in qMEP metrics.; Results:; Expanded Disability Status Scale and ambulation score progressed in the rANOVA model (; p; < 0.05;; post-hoc; comparison baseline-year 2,; p; < 0.1). Lower limb and combined qMEP scores showed significant deterioration of latency (; p; < 0.01, MEP-LL_CxM-sh:; p; < 0.05) and in; post-hoc; comparisons (baseline-year 2,; p; < 0.05), qMEP_CxM-mn even over 1 year (; p; < 0.05). Effect sizes were higher for qMEP scores than for clinical measures, and slightly but consistently higher when based on CxM-mn compared to CxM-sh or CMCT. Subgroup analysis yielded no indication of higher sensitivity of timed clinical measures over qMEP scores. Two independent factors were detected, the first mainly associated with qMEP-LL, the second with qMEP-UL, explaining 65 and 29% of total variability, respectively.; Conclusions:; Deterioration in qMEP scores occurs earlier than EDSS progression in patients with PPMS. Upper and lower limb qMEP scores contribute independently to measuring change, and qMEP scores based on mean CxM are advantageous. The capability to detect subclinical changes longitudinally is a unique property of EP and complementary to clinical assessment. These features underline the role of EP as candidate biomarkers to measure effects of therapeutic interventions in PPMS

Machine translation of TV subtitles for large scale production

This paper describes our work on building and employing Statistical Machine Translation systems for TV subtitles in Scandinavia. We have built translation systems for Danish, English, Norwegian and Swedish. They are used in daily subtitle production and translate large volumes. As an example we report on our evaluation results for three TV genres. We discuss our lessons learned in the system development process which shed interesting light on the practical use of Machine Translation technology

Adaptation of antiretroviral therapy in human immunodeficiency virus infection with central nervous system involvement

The authors describe a patient with known human immunodeficiency virus (HIV)-1 infection who presented with two generalized seizures and was found to have extensive white matter disease and a left/bilateral temporo-occipital focal slowing on electroencephalography (EEG). There were no magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF) indications for opportunistic infection. Plasma viremia was controlled, whereas viral replication was uncontrolled in CSF. CSF-specific genotype-guided adaptation of the antiretroviral therapy in order to optimize central nervous system (CNS) penetration resulted in clinical improvement and normalization of MRI and EEG. Our case report illustrates the importance of individualized antiretroviral therapy in HIV infected patients with neurological complication

Multicentre assessment of motor and sensory evoked potentials in multiple sclerosis : reliability and implications for clinical trials

Motor and sensory evoked potentials (EP) are potential candidate biomarkers for clinical trials in multiple sclerosis.; To determine test -retest reliability of motor EP (MEP) and sensory EP (SEP) and associated EP-scores in patients with multiple sclerosis.; In three centres, 16 relapsing and five progressive multiple sclerosis patients had MEPs and SEPs 1-29 days apart. Five neurophysiologists independently marked latencies by central reading. By variance component analysis, we estimated the critical difference (absolute reliability) for cross-sectional group comparison, comparison of longitudinal group changes, within-subject minimal detectable change and defined within-subject improvement.; Cortical SEP responses and cortico-muscular MEP latencies were more reliable than central conduction times. For comparison of 20 subjects per arm, cross-sectional group difference ranged from 0.7 to 3.9 ms and 1.1 to 1.7, group difference in longitudinal changes from 0.4 to 1.8 ms and 0.36 to 0.62, within-subject minimal detectable change from 1.2 to 5.8 ms and 1.2 to 2.0, within-subject improvement from 0.8 to 3.8ms and 0.8 to 1.3, for single EP modalities and EP scores, respectively.; Multicentre EP assessment with central EP reading is feasible and reliable. The critical difference is reasonably low to detect significant group changes and to define responders. The results support the concept of using EP and EP-scores as candidate response biomarkers for quantification of disease progression and for studying remyelination in multiple sclerosis

Improved Characterization of Visual Evoked Potentials in Multiple Sclerosis by Topographic Analysis

In multiple sclerosis (MS), the combination of visual, somatosensory and motor evoked potentials (EP) has been shown to be highly correlated with the Expanded Disability Severity Scale (EDSS) and to predict the disease course. In the present study, we explored whether the significance of the visual EP (VEP) can be improved with multichannel recordings (204 electrodes) and topographic analysis (tVEP). VEPs were analyzed in 83 MS patients (median EDSS 2.0; 52% with history of optic neuritis; hON) and 47 healthy controls (HC). TVEP components were automatically defined on the basis of spatial similarity between the scalp potential fields (topographic maps) of single subjects' VEPs and reference maps generated from HC. Non-ambiguous measures of latency, amplitude and configuration were derived from the maps reflecting the P100 component. TVEP was compared to conventional analysis (cVEP) with respect to reliability in HC, validity using descriptors of logistic regression models, and sensitivity derived from receiver operating characteristics curves. In tVEP, reliability tended to be higher for measurement of amplitude (p=0.06). Regression models on diagnosis (MS vs. HC) and hON were more favorable using tVEP- versus cVEP-predictors. Sensitivity was increased in tVEP versus cVEP: 72% versus 60% for diagnosis, and 88% versus 77% for hON. The advantage of tVEP was most pronounced in pathological VEPs, in which cVEPs were often ambiguous. TVEP is a reliable, valid, and sensitive method of objectively quantifying pathological VEP in particular. In combination with other EP modalities, tVEP may improve the monitoring of disease course in MS

Dysfunction in Early Multiple Sclerosis: Altered Centrality Derived from Resting-State Functional Connectivity Using Magneto-Encephalography

BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) is frequent. Insight into underlying mechanisms would help to develop therapeutic strategies. OBJECTIVE: To explore the relationship of cognitive performance to patterns of nodal centrality derived from magneto-encephalography (MEG). METHODS: 34 early relapsing-remitting MS patients (median EDSS 2.0) and 28 age- and gender-matched healthy controls (HC) had a MEG, a neuropsychological assessment and structural MRI. Resting-state functional connectivity was determined by the synchronization likelihood. Eigenvector Centrality (EC) was used to quantify for each sensor its connectivity and importance within the network. A cognition-score was calculated, and normalized grey and white matter volumes were determined. EC was compared per sensor and frequency band between groups using permutation testing, and related to cognition. RESULTS: Patients had lower grey and white matter volumes than HC, male patients lower cognitive performance than female patients. In HC, EC distribution showed highest nodal centrality over bi-parietal sensors ("hubs"). In patients, nodal centrality was even higher bi-parietally (theta-band) but markedly lower left temporally (upper alpha- and beta-band). Lower cognitive performance correlated to decreased nodal centrality over left temporal (lower alpha-band) and right temporal (beta-band) sensors, and to increased nodal centrality over right parieto-temporal sensors (beta-band). Network changes were most pronounced in male patients. CONCLUSIONS: Partial functional disconnection of the temporal regions was associated with cognitive dysfunction in MS; increased centrality in parietal hubs may reflect a shift from temporal to possibly less efficient parietal processing. To better understand patterns and dynamics of these network changes, longitudinal studies are warranted, also addressing the influence of gender

Discourse structure and language technology

This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.An increasing number of researchers and practitioners in Natural Language Engineering face the prospect of having to work with entire texts, rather than individual sentences. While it is clear that text must have useful structure, its nature may be less clear, making it more difficult to exploit in applications. This survey of work on discourse structure thus provides a primer on the bases of which discourse is structured along with some of their formal properties. It then lays out the current state-of-the-art with respect to algorithms for recognizing these different structures, and how these algorithms are currently being used in Language Technology applications. After identifying resources that should prove useful in improving algorithm performance across a range of languages, we conclude by speculating on future discourse structure-enabled technology.Peer Reviewe

Whole-scalp EEG mapping of somatosensory evoked potentials in macaque monkeys

High-density scalp EEG recordings are widely used to study whole-brain neuronal networks in humans non-invasively. Here, we validate EEG mapping of somatosensory evoked potentials (SSEPs) in macaque monkeys (Macaca fascicularis) for the long-term investigation of large-scale neuronal networks and their reorganisation after lesions requiring a craniotomy. SSEPs were acquired from 33 scalp electrodes in five adult anaesthetized animals after electrical median or tibial nerve stimulation. SSEP scalp potential maps were identified by cluster analysis and identified in individual recordings. A distributed, linear inverse solution was used to estimate the intracortical sources of the scalp potentials. SSEPs were characterised by a sequence of components with unique scalp topographies. Source analysis confirmed that median nerve SSEP component maps were in accordance with the somatotopic organisation of the sensorimotor cortex. Most importantly, SSEP recordings were stable both intra- and interindividually. We aim to apply this method to the study of recovery and reorganisation of large-scale neuronal networks following a focal cortical lesion requiring a craniotomy. As a prerequisite, the present study demonstrated that a 300-mm2 unilateral craniotomy over the sensorimotor cortex necessary to induce a cortical lesion, followed by bone flap repositioning, suture and gap plugging with calcium phosphate cement, did not induce major distortions of the SSEPs. In conclusion, SSEPs can be successfully and reproducibly recorded from high-density EEG caps in macaque monkeys before and after a craniotomy, opening new possibilities for the long-term follow-up of the cortical reorganisation of large-scale networks in macaque monkeys after a cortical lesion

Using linguistic annotations in statistical machine translation of film subtitles

Statistical Machine Translation (SMT) has been successfully employed to support translation of film subtitles. We explore the integration of Constraint Grammar corpus annotations into a Swedish–Danish subtitle SMT system in the framework of factored SMT. While the usefulness of the annotations is limited with large amounts of parallel data, we show that linguistic annotations can increase the gains in translation quality when monolingual data in the target language is added to an SMT system based on a small parallel corpus