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In the routine recording of magnetocardiograms (MCGs), it is necessary to underline the problem of noise cancellation. Source separation has often been suggested to solve this problem. In this paper, blind source separation (BSS), by means of singular value decomposition (SVD) and independent component analysis (ICA), was used for noise reduction in MCG data to improve the signal to noise ratio. Special techniques, based on statistical parameters, for identifying noise and disturbances, have been introduced to automatically eliminate noise-related and disturbance-related components before reconstructing cleaned data sets. The results show that ICA and SVD can detect and remove a variety of noise and artefact sources from MCG data, as well as from stress MCG. [ABSTRACT FROM AUTHOR]

Background and purpose: Ultrasound is a useful non-invasive instrument in visualizing physiological and pathological morphology in skeletal muscle. Here, we evaluate the possibility that quantitative muscle ultrasound using the parameters ‘intensity’, ‘entropy’, and ‘fractal dimension’ is a feasible method to distinguish between dystrophic myopathies (DM), inflammatory myopathies (IM), and motor neuron disorders. Methods: Seven patients with IM, 12 patients with DM, nine patients with motor neuron diseases, and 24 healthy subjects underwent an identical ultrasound examination protocol, applied on gastrocnemius and tibialis anterior muscle. Analysis parameters were applied on grey scale images as well as on gradient images. Results: Statistical evaluation revealed no significant differences in the evaluated parameters for differentiation of the distinct disease groups. Compared with healthy controls however we found statistically significant differences between almost of all the investigated parameters, even in disease cases with clinically unaffected distal musculature. Conclusion: The parameters are able to distinguish between healthy and affected musculature but not between distinct disease entities. Studies are needed to establish whether or not the parameters are helpful to monitor muscle involvement and disease progression in neuromuscular diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible association of a distinct combination of polymorphisms in the interleukin (IL)-1 gene cluster on gingival bleeding tendency in young adult Arabs with plaque-induced gingivitis. Fifty otherwise healthy, nonsmoking volunteers, 19–28 years of age, participated. Clinical examinations included periodontal probing depth, bleeding on probing, and plaque index. Probing was done with a pressure-controlled probe at about 1.27 MPa. Examinations were repeated after 2 and 4 weeks. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. A subject carrying alleles 2 at IL-1A −889 and IL-1B +3954 was designated genotype-positive. Twenty-six subjects were genotype-positive (52%). A repeated measures two-level (occasion, subject) model of the proportion of sites bleeding on probing, which was adjusted for gender, average plaque index, probing depth, and calculus, revealed a significantly lower proportion of bleeding sites in genotype-positive subjects (estimate −0.050, standard error 0.025, p < 0.05). Biserial correlations of bleeding proportions were high (0.71–0.78), confirming the steady-state plaque environment. It was concluded that inflammatory responses to dental plaque were considerably dampened in genotype-positive, nonsmoking young adults of Arabic heritage. [ABSTRACT FROM AUTHOR]

Abstract: In 1992, Brockmeier et al. showed the difference in magnetocardiography (MCG)-detected field distribution generated by the heart at rest and under stress. Unfortunately, routinely recorded magnetocardiograms (MCGs) are corrupted by different types of artifacts, especially during stress. This work addressed the problem of optimizing artifacts removing and improving the signal to noise ratio (SNR) in patients with coronary heart disease (CHD) under pharmacological stress MCG (PSMCG) using a technique of Blind Source Separation (BSS) called TDSEP. Techniques based on simple statistical parameters were proposed to identify the cardiac related component among the unmixed data. The presented results showed that BSS could detect and remove a variety of noise and artifact sources in PSMCG, allowing the use in clinical applications. [Copyright &y& Elsevier]

Abstract: The field distribution generated by the heart and detected by magnetocardiography (MCG) shows strong effects, comparing the field distribution at rest and under stress. To study the possible clinical application, it is convenient to avoid pharmacological stress and perform Stress MCG (SMCG) using conventional physical stress with an ergometer. Unfortunately the subject movements and the ergometer residual artefacts produce extra noise and disturbances which should be eliminated. For this purpose 4 different Blind Source Separation (BSS) algorithms were tested: fastICA, TDSEP, JADE and SHIBBS. The algorithms were applied on 12 SMCG data sets for the task to de-noise them. The correlation between odd and even beats (using the simultaneously recorded electrocardiogram (ECG)) and the known spectral content were considered for automatically detecting noise and disturbances. All the methods were able to detect the ergometer noise. The best results were achieved by TDSEP, both in computation time and in goodness of separation. This work shows that, with BSS, the extraction of heart signals from ergometer SMCG data is becoming feasible. [Copyright &y& Elsevier]

Multivariate multilevel modeling was applied to analyze repeated measures data on the influence of heavy smoking on the association between the amount of supragingival plaque and gingival bleeding on probing (BOP) in a steady-state plaque environment. Data acquired in 65 systemically healthy young adults with mild plaque-induced gingivitis were analyzed. 33 heavy smokers consumed at least 20 cigarettes per day while 32 were non-smokers. Periodontal examinations at the outset consisted of periodontal probing depth, clinical attachment level, BOP, plaque index, and presence of calculus at 6 sites of every tooth present. They were repeated 3 times every 8 weeks. A multivariate 4-level variance component model revealed that the odds of BOP was twice as high in smokers. In addition, females had a lower likelihood for BOP but, with increasing bleeding scores during the course of the study, this effect attenuated. Low biserial correlations for BOP at the site level of between 0.11 and 0.2 were found. At the tooth level, correlations were moderate (0.2–0.5), and highest at the subject level (0.8–0.9). Variations at subject and tooth levels were very large at the outset but notably attenuated in the course of the study. Plaque consistently influenced the tendency for BOP with an odds ratio of about 1.7–1.8 for each increase in score in both smokers and non-smokers. The present study did not reveal evidence for attenuation of the plaque/gingival bleeding relationship in heavy smokers. [ABSTRACT FROM AUTHOR]

Aim: To study longitudinal associations between plaque and gingival bleeding and multilevel variance/covariance structures after introducing triclosan-containing toothpaste. Material and Methods: A 10-week, randomized, two-arm, double-masked, controlled clinical trial was conducted in 34 healthy, non-smoking females with plaque-induced gingivitis. Clinical periodontal examinations were repeated every other week. At week 4, test toothpaste containing 0.24% sodium monofluorophosphate, 0.3% triclosan, and 2% polyvinyl–methyl ether maleic acid; or control toothpaste containing 0.76% sodium monofluorophosphate and 0.1% sodium fluoride, were randomly distributed. Results: Multivariate multilevel models indicated that, after introducing experimental toothpastes, subject random error was reduced from 0.6 to below 0.2. The odds ratio (OR) of bleeding on probing (BOP) was about 30% less in the test than in the control group ( p<0.01). At the end of the experiment, ORs for BOP and plaque index scores 1–3 (reference 0) were 2.1–2.4 in the control group, but 1.1–1.9 in the test group ( p<0.05). No effects on plaque levels and calculus were observed. Conclusions: Multivariate multilevel modelling allows the study of fixed and random effects of experimental toothpastes on gingival inflammation in small sample. Triclosan appears to attenuate the causal association between supragingival plaque and gingival bleeding in gingivitis. [ABSTRACT FROM AUTHOR]

In 1992, Brockmeier et al . showed that there is a strong difference in magnetocardiography (MCG)-detected field distribution generated by the heart at rest and under stress. To study the possible clinical applications of this finding, it is convenient to avoid pharmacological stress and to perform stress MCG (SMCG) using conventional physical stress with an ergometer. When using a non-magnetic ergometer, the MCG recordings under physical stress are more noisy due to the unavoidable movement artefacts from the patient and from the residual artefacts of the ergometer. To remove these artefacts a denoising was performed using independent component analysis (ICA) in a new implementation. This work shows that with ICA in this special implementation it is becoming feasible to extract heart signals from SMCG data recorded during ergometer exercise. [ABSTRACT FROM AUTHOR]

Abstract: To analyze functional magnetic resonance imaging (fMRI) data sets, the physiologically induced signals have to be separated from noise or from artifacts as a result of involuntary patient motion or MRI detection techniques. In the past years various methods of analysis of fMRI data were proposed, however one of the unsolved problems is related to dependence of the results with the threshold applied within each analysis. An alternative fMRI time series analysis method based on information theory and Tsallis entropy is proposed to decrease this dependency. The method applies the generalized mutual information (GMI) concept. Within the fMRI framework the GMI between the hemodynamic response function of a given voxel and the paradigm slope is evaluated as a measure of the amount of information that the paradigm could be encoded by a given brain region or voxel. This value represented the activation of the voxels. However, the analysis relies heavily on the Tsallis parameter, allowing for a broad spectrum of results. As a test of applicability of the method real fMRI data were obtained in a simple motor paradigm and subsequently analyzed with GMI for several values of a as well as with classical methods (cross-correlation and Student''s -test). The simulated data were used to compare quantitatively the presented method with the classical ones by means of the construction of receiver operating characteristic (ROC) curve. The results showed the applicability of the GMI method as well as the range of optimum -values. [Copyright &y& Elsevier]

The main objective of analyzing functional magnetic resonance imaging (fMRI) data sets is to screen the physiologically induced signals from noise or artifacts resulting either from involuntary patient motion or MRI detection techniques. One problem, that is not yet solved, is related to the dependency of the results in regard to the threshold applied within each analysis. Recently, an alternative fMRI time series analysis method has been proposed to decrease the dependency of the results with the applied threshold. This method is based on the calculation of the generalized mutual information (GMI) between the blood oxygenation level dependence time series and the paradigm slope. Since the analysis relies heavily on the Tsallis q parameter, a broad spectrum of results can be produced. So simulated data analysis was performed in order to construct the receiver operating characteristic curves. The parameters that evaluate the quality of the curves were determined thus allowing for an optimization of the q values. Results for simulated and real fMRI data were compared for both GMI and classical deterministic analysis. [Copyright &y& Elsevier]

Parameterization of the ST-segment is used as a tool for risk stratification for patients to suffer from ventricular tachycardia. This parameterization is performed in terms of Principal Component Analysis (PCA) applied on multichannel magnetocardiographic (MCG) recordings. 55-channel MCG was recorded from 14 normal persons, 10 patients with CHD, 14 patients with MI, and six patients with VT. We found a significantly (p < 0.05) lower PCA-score in patients with MI compared to normals. The lowest PCA-score was found in VT patients. Significant differences can be found between VT patients and normals and also between VT patients and CHD patients. [ABSTRACT FROM AUTHOR]

High resolution electrocardiography (HRECG) recordings have already shown an increased beat-to-beat microvariability of the QRS duration of the terminal QRS in patients with a history of ventricular tachycardia (VT). The purpose of this study is to detect QRS-duration microvariability with magnetocardiographic (MCG) recordings in normals, patients with coronary heart disease (CHD), patients with a history of myocardial infarction (MI), and VT patients. QRS microvariability is calculated as the variance of time- shifts of single beats respectively to the average of all beats. The average over all channels of the MCG is performed. QRS microvariability was evaluated from 55-channel MCG in 15 normal persons, in 12 patients with CHD, in 13 patients with MI, and in 10 patients with VT. We found a significantly higher microvariability in patients with MI compared to normals. The highest microvariability was found in VT patients. [ABSTRACT FROM AUTHOR]

Background/aims: Periodontal infections with Actinobacillus actinomycetemcomitans seem to be refractory to conventional therapy. The aim of the present study was to test the in vitro susceptibilities of A. actinomycetemcomitans strains to a panel of seven orally administrable antibiotics. Methods: A total of 60 isolates of A. actinomycetemcomitans recovered from 43 individuals with gingivitis or periodontitis were tested. In addition, laboratory strains UP-6 and JP2 were analysed. The E-test was employed in order to determine minimal inhibitory concentrations (MIC) of antibiotics ampicillin/sulbactam, roxithromycin, azithromycin, doxycycline, metronidazole, ciprofloxacin, and moxifloxacin. Results: A. actinomycetemcomitans was highly susceptible to both fluoroquinolones (MIC[SUB90] of 0.006 μg/mL of ciprofloxacin and 0.032 μg/mL of moxifloxacin). Good susceptibilities were found for ampicillin/sulbactam and doxycycline (MIC[SUB90] of 0.75 μg/mL and 1 μg/mL, respectively), and moderate susceptibilities for azithromycin (MIC[SUB90] of 3 μg/mL). Most strains were resistant to metronidazole and roxithromycin. Cluster analysis revealed two larger clusters of A. actinomycetemcomitans strains with the smaller cluster assembling isolates with significantly higher MICs of most antibiotics. Conclusions: Due to reported favourable pharmacokinetics, the fluoro-quinolone moxifloxacin appeared to be a promising candidate for adjunctive systemic antibiotic therapy in periodontal infections with A. actinomycetemcomitans. [ABSTRACT FROM AUTHOR]

The objectives of the present study were (I) to determine the validity and reliability of measuring gingival thickness (GTH) with a recently developed, commercially available ultrasonic device; (II) to measure GTH in relation to tooth type and age of proband; (III) to correlate GTH with varying forms of premolars, canines and incisors. Ultrasonic measurements were performed in 200 periodontally healthy, male probands representing 3 different age groups (20-25, 40-45, 55-60 years). In the maxilla, mean GTH varied between 0.9 mm (canines, 1st molars) and 1.3 mm (2nd molars). In the mandible respective mean values ranged between 0.8 mm (canines) and 1.5 mm (2nd molars). No differences in means and standard deviations (0.36-0.39 mm) were observed in different age groups. In order to correlate GTH with other clinical parameters and form of tooth, in 42 probands of the youngest age group, presenting with no attrition or abrasion, no artificial crown restorations and (following prophylaxis) no overt gingivitis and no periodontal probing depth in excess of 3 mm, detailed clinical measurements and stone model cast analyses were performed. By stepwise multiple linear regression analysis, 24% (p < 0.0001) of the variation of GTH was explained by probing depth, recession, width of gingiva and tooth type. The ratio of the width of the crown to its length was not included into the model. When performing analysis of covariance with the subject as factor, the model was improved, now explaining 41% of the variation of GTH. In this model, the influence of periodontal probing depth was decreased, and recession was not included. It was concluded that there are individual differences in GTH (i.e., different biotypes). However, thickness mainly depends on tooth type and is correlated with width of gingiva. There appears to be no association with shape and form of the tooth. Validity and reliability of measuring GTH with the ultrasonic device was found to be excellent. [ABSTRACT FROM AUTHOR]

In the present study, data from more than 550 periodontally diseased patients with more than 1100 furcation invasions were retrospectively analysed. There were apparent differences in the distribution of different furcation degrees in patient populations treated by 2 differently experienced operators. However, treatment modality patterns were rather similar. Scaling during periodontal flap surgery was the most often performed treatment procedure in degree I (97-98%) and II (75-83%) involvement. About 44% of degree III involved teeth were extracted. In order to determine the influence of degree of furcation involvement, tooth type and operator variability on treatment modality, logistic regression analysis was applied. Degree of furcation involvement was an important indicator variable in all models. Scaling as a sole measure was mainly performed in relation to degree I of furcation involvement. With every increase in degree, the odds of scaling decreased by factor 12.7. The odds of root resection was upper 1st molars 46× higher than in wisdom teeth or lower 2nd molars with the same degree of involvement, but only 3.3× higher than in lower 1st molars. Tunnel preparation as well as regeneratire procedures were mainly confined to lower molars. Operator variability was only introduced as a covariate in the extractionmodel. Hence, despite of different operator skill and severity of periodontal disease in treated populations, decision for one or the other treatment modality seems to depend essentially on degree of furcation involvement as well as tooth type. [ABSTRACT FROM AUTHOR]

In the present study, a total of 619 subgingival and extracrevicular samples from 66 early-onset periodontitis, 42 adult periodontitis/gingivitis and 36 treated Actinobacillus actinomycetemcomitans-associated periodontitis patients were selectively cultivated for presence of A. actinomyctemcomitans. The organism was recovered from 68% cases with early-onset periodontitis, 24% cases with adult periodontitis/gingivitis and 50% of treated patients. Associations between recovery from pooled subgingival plaque and samples from extracrevicular locatins as well as between different extracrevicular samples, were not heterogeneous with regard to different groups with the exception for cheek/saliva comparisons (odds ratios: early-onset periodontitis 825; adult periodontitis 8.1, treated patients 117; 0.05 <p<0.1). For associations between recovery of A. actinomycetemcomitans from pooled subgingival plaque/extracrevicular samples, Mantel-Haenszel's odds ratios of between 12.2 an d21.6 were calculated (p<0.0001). The organism was isolated from 17 cheek mucosa samples of 18 patients identified as still harboring the organism after therapy. Present results point to the considerable value of cheek mucosa samples especially in treated patients to diagnose persistent A. actinomycetemcomitans colonization of the oral cavity. [ABSTRACT FROM AUTHOR]

Infrequent occurrence of spirochetes and rather low proportions of these organisms have been reported in localized juvenile periodontitis, where periodontal lesions often harbour large numbers of Actinobacillus actinomycetemcomitans, a suspected principal periopathogen strongly implicated in the pathogenesis of this and other forms of chronic periodontitis. We studied the association of subgingival A. actinomycetemcomitans with the morphological composition of the subgingival microbiota in a large population of patients suffering from advanced periodontitis. Subgingival plaque from the deepest pockets of every quadrant of their dentitions was sampled and pooled in 70 patients between 14 and 63 years of age, and analysed morphologically by phase-contrast microscopy. A minimum % similarity index was employed to define 4 clusters with different morphological composition of the floras. The actual proportion of A. actinomycetemcomitans was determined at 2 sites with deep periodontal pockets. All clusters harboured patients infected with A. actinomycetemcomitans. If present, in clusters predominated by motile rods or medium-sized spirochetes, the organism was found in rather low proportions (median 5.3% and 3.4%, respectively). However, the cluster with a pooled flora mainly consisting of coccoid cells revealed periodontal sites with A. actinomycetemcomitans in proportions of more than 53% (median), if the organism was present (p<0.01). We found a positive correlation between proportions of A. actinomycetemcomitans and cocci (R=0.65) and negative correlations with spirochetes and motile rods (R=-0.61, R=-0.59, respectively). Cautious interpretation of subgingival plaque predominated by coccoid cells is recommended, if deep periodontal pockets and obvious signs of inflammation are present, since these pockets were found to be often infected with large numbers of A. actinomycetemcomitans. [ABSTRACT FROM AUTHOR]

The composition of subgingival plaque, from healthy and periodontally diseased regions, as well as the clinical periodontal condition of 6 patients, 17 to 24-years-old suffering from juvenile periodontitis were examined. 6 older patients with rapidly progressive periodontitis served as a control. Samples of subgingival plaque were taken from first molars and central incisors and were analysed morphologically by dark-field microscopy. In the control group in healthy regions the ratio between non-motile and motile bacteria was 27:1 and about 1:1 in deep pockets. In the juvenile periodontitis group in diseased regions, motile bacteria made up only ¼ of the bacteria present. The results clearly show that our relatively old patients with juvenile periodontitis had a completely different microflora in their periodontally diseased regions than patients with common periodontitis. As regards our observations by dark-field microscopy, one can assume, however, that with increasing age, there might be a shift of the flora associated with juvenile periodontitis lesions from a rather simple composition to a more complex composition very similar to the flora seen in rapidly progressive adult periodontitis lesions. [ABSTRACT FROM AUTHOR]

Introduction Recently, the characteristic longitudinal distribution pattern of the underlying phosphorylated TDP-43 (pTDP-43) pathology in the behavioral variant of frontotemporal dementia (bvFTD) across specific brain regions was described ( Brettschneider et al., 2013 ). The aim of the present study was the transfer of these neuropathological findings to a diffusion tensor imaging (DTI)-based in vivo staging protocol. Methods Thirty-one bvFTD patients and 49 controls underwent DTI in a bicentric study design. Out of these, 14 bvFTD patients and 17 controls had a follow-up scan after 12 months. A second follow-up scan was performed in 4 bvFTD patients and in 7 controls, again after 12 months. Cross-sectional and longitudinal alterations were assessed by a two-fold analysis, i.e. voxelwise comparison of fractional anisotropy (FA) maps and a tract of interest-based (TOI) approach, which identifies tract structures that could be assigned to brain regions associated with disease progression ( Kassubek et al., 2014 ). Results Cross-sectional whole brain-based spatial statistics showed white matter alterations predominantly in the frontal lobes but no longitudinal alterations. The TOIs of bvFTD-stages 1 and 2 (uncinate fascicle – bvFTD-pattern I; corticostriatal pathway – bvFTD-pattern II) showed highly significant differences between bvFTD patients and controls. The corticospinal tract-associated TOI (bvFTD-pattern III) did not differ between groups in this group, whereas the differences in the optic radiation (bvFTD-pattern IV) were significant. Longitudinal TOI analysis allowed for individual patient categorization of one subgroup according to the pTDP-43 staging scheme. Longitudinally, disease progression ( N = 5) or stable stage ( N = 5) were observed. Conclusion The TOI-based in vivo staging approach was successfully applied to bvFTD and demonstrated a plausible pattern of damage to the involved major white matter pathways. Therefore, the TOI-based staging approach may also have potential as an in vivo biomarker for bvFTD. [ABSTRACT FROM AUTHOR]

Background Recordings of eye movements have demonstrated that oculomotor dysfunction in patients with amyotrophic lateral sclerosis (ALS) follows a two-staged pattern ( Gorges et al., 2015 ) that is consistent with the model of sequential corticofugal axonal spread of pTDP-43 pathology ( Brettschneider et al., 2013 ). Eye movement abnormalities in ALS include anti- and delayed saccades errors (stage 1) as well as additional infratentorial-network associated oculomotor functions such as gaze-palsy or a cerebellar type of smooth pursuit disturbance (stage 2). We aimed to investigate whether this model can be confirmed in a larger cohort ( N = 164) and in longitudinal testing. Methods Eye movement recordings using video-oculography (EyeSeeCam®) together with clinical (ALS-FRS) and neuropsychological scores (ECAS) from 164 ALS patients and 31 matched healthy controls were used for the analysis. Longitudinal data were available from 16 ALS patients ( ∼ 6 months after initial testing). Results At the time of the first investigation, 60 patients presented no oculomotor deficits (‘nd’) compared with controls. 78 patients showed stage 1 symptoms with only executive dysfunction and 26 patients showed stage 2 pathology with additional cerebellar type of smooth pursuit and/or gaze palsy. The sequential appearance of impaired eye movement control as hypothesized by Gorges et al. (2015) was confirmed by the categorization of eye movement abnormalities over time: four patients with no deficits at timepoint 1 (out of 16) developed only executive dysfunctions ( nd ⩾ stage 1) and one patient (categorized as stage 1 at timepoint 1) developed to stage 2, accompanied by a gradual worsening of executive functions. The oculomotor stages were significantly correlated (p). Conclusion According to the cross sectional approach the model of a two-staged sequential pattern of eye movement abnormalities in ALS could be confirmed by a lager cohort. Additional preliminary longitudinal data in 16 patients showed a progression from stage 0 to 1 or from 1 to 2 respectively. Thus our data favor the hypothesis that oculomotor decline in ALS depicts the neuropathological sequential spreading of the disease instead of being the consequence of different phenotypes of ALS. Oculomotor staging may serve as a technical marker of the neuropathological disease progression in correlation to the clinical phenotype. [ABSTRACT FROM AUTHOR]

Objective To investigate whether impaired eye movement control as a common non-motor manifestation in Parkinson’s disease (PD) is associated with alterations of intrinsic functional connectivity. Methods We recorded smooth pursuit and saccadic eye movements using video-oculography and ‘resting-state’ fMRI in 31 PD patients and 22 matched healthy controls. Eye movement parameters were correlated with functional connectivity measures in-between connectivity networks. Results In agreement with the present literature, oculomotor deficits in PD included interrupted smooth pursuit, hypometric saccades, and increased error rate in anti-saccades. We demonstrated significant correlations between eye movement parameters and functional connectivity measures, i.e. the functional connectivity declined with disturbed eye movement performance. Connectivity between major nodes of the default mode network was strongly correlated with the rate of saccadic intrusions as a measure of executive function. Conclusions Oculomotor deficits in PD appear to be predominantly associated with executive dysfunctions and to be attributable to impaired higher functional networks rather than to brainstem oculomotor circuitry. These results support the notion that dopamine depletion alone is insufficient to explain executive oculomotor abnormalities in PD. Key message Deficits in eye movement control in PD may reflect a behavioral correlate of altered intrinsic brain activity within cortical function networks. [ABSTRACT FROM AUTHOR]

Objective To see whether the sequential corticofugal spreading of pTDP-43 pathology in amyotrophic lateral sclerosis (ALS) (Brettschneider et al., Ann Neurol 2013) permit the categorization of eye movement disturbances in a corresponding oculomotor staging scheme. Methods Saccadic and smooth pursuit eye movements were video-oculographically recorded from 68 ALS patients and 31 matched healthy controls in order to compute parameters for executive oculomotor functions and brainstem oculomotor circuitry performance. Results Thirty patients had no oculomotor abnormalities compared to controls, all other presented a broad spectrum of impaired eye movement control including increased anti- and delayed saccades errors, a high prevalence of saccadic intrusions, gaze-palsy and a cerebellar type of smooth pursuit disturbance. Oculomotor deficits manifested sequentially witch permits a categorization of two stages: Stage 1, exclusively executive dysfunctions, and Stage 2, executive deficits plus impaired ,genuine‘ oculomotor control such as gaze-palsy or impaired pre-cereballary circuits. Conclusions Impaired executive eye movements appear as the initial manifestation, followed by disturbed infratentorial oculomotor control pathways. Key message Alterations in eye movement control in ALS follow a sequential pattern and may serve as a technical marker of the corticofugal axonal spread of the disease. [ABSTRACT FROM AUTHOR]

Introduction Eye movements provide a valuable window into complex forms of human behavior. Impaired eye movement control in patients with Parkinson’s disease (PD) has been consistently demonstrated besides the well-known motor symptoms ( Pinkhardt and Kassubek, 2011 ). Saccadic intrusions are a common oculomotor manifestation in PD and interrupt smooth pursuit and fixation during tracking a ’jumping’ target (visually guided reactive saccades) ( Pinkhardt and Kassubek, 2011; Gorges et al., 2014 ). The default mode network (DMN) as observed with ’resting-state’ functional MRI is crucially involved in higher cognitive processes such as attention ( Buckner et al., 2008 ). We hypothesized that prevalence of saccadic intrusions in patients with PD reflects executive deficits which are closely associated with intrinsic functional connectivity (iFC) within the DMN. Methods The analysis was based on 31 patients with PD and 22 age-matched healthy controls. We acquired ’resting-state’ functional MRI (3 Tesla; BOLD-sensitive T2 ∗ -sequence) and video-oculographic recordings (VOG, Eye-Link I operating on 250 Hz sampling rate) of smooth pursuit eye movements and visually guided reactive saccades. ’Resting-state’ functional MRI analysis followed standardized procedures ( Gorges et al., 2014 ) with the DMN computed by seeding the posterior cingulate cortex ( Buckner et al., 2008 ). The posterior cingulate cortex is known to be both a major node of the DMN ( Buckner et al., 2008 ) and to play a critical role in eye movement control ( Olson et al., 1996 ). Both smooth pursuit gain as a measure for saccadic intrusions and the saccadic intrusion rate during reactive saccades were analyzed in patients vs. controls and correlated with iFC within the DMN. Results VOG analysis revealed a significantly higher prevalence of saccadic intrusions during smooth pursuit ( p < 0.001) and reactive saccades ( p < 0.01) in PD patients compared with controls. Covariance analysis between the saccadic intrusion measures and the iFC in the DMN demonstrated significantly negative correlations ( p < 0.001 for all clusters, corrected for multiple comparisons) in the sense that reduced iFC in almost all parts of the DMN was related to a higher prevalence of saccadic intrusions. Specifically, iFC between the posterior cingulate cortex and the (i) middle temporal lobe, (ii) thalamus, (iii) MST, (vi) precuneus (v), medial prefrontal cortex, and (vi) parietal lobule were significantly correlated with the saccadic intrusion rates. Conclusions A high prevalence of saccadic intrusions in patients with PD appears to be closely related to a lack of attention, pointing towards an increased distractibility that might be associated with the neuroimaging correlate of a disrupted DMN. This supports the hypothesis that impaired oculomotor control in PD reflects a behavioral correlate of disturbed higher functions rather than impaired oculomotor circuits in the brainstem. [ABSTRACT FROM AUTHOR]

Introduction Diffusion tensor imaging (DTI)-based metrics are increasingly used for analyzing ALS-associated whitematter alteration patterns and were included inthe Neuroimaging Society in Amyotrophic Lateral Sclerosis (NiSALS) concept ( Turner et al., 2011 ). The objective of this multicenter study was to assess structural connectivity in ALS at a large sample size to address the challenges of DTI data analysis from multiple study sites. Methods Four-hundred and ninety DTI data sets from patients with ALS ( N = 268) and controls ( N = 222) were collected from 8 study centers (Dublin, Ireland; Edinborough, UK; Jena, Germany; Miami, US; Milan, Italy; Oxford, UK; Rostock, Germany, Ulm, Germany). Data were obtained by different MRI-systems and by use of different DTI-protocols. In a first step, comparability of data with the aim of pooling was tested by a statistical analysis of fractional anisotropy (FA) in controls’ data. All analyses were performed by use of the Tensor Imaging and Fiber Tracking (TIFT) software. Statistical comparisons in terms of average FA-values ( Müller et al., 2013 ) were performed for the controls’ groups of the different centers. In a consecutive step, the calculated 3D correction matrices were then applied to the corresponding ALS patient subgroups of the different centers. Results Data collection and data quality control resulted in 442 DTI data sets (253 ALS patients and 189 controls) useful for this study, i.e. 48 data sets had to be excluded. All data samples of all centers showed a characteristic pattern (FA decrease along the corticospinal tracts) for comparison at the group level. Inter-center pooling of data showed ALS affectations in the CST (“horseshoe” configuration) as well as affectations in regions that have recently been reported to be relevant in ALS (frontocortical whitematter regions, hippocampal regions, as well as midbrain and brainstem) ( Kassubek et al., 2014 ). Conclusion This large scale multicenter NiSALS study investigated solutions to challenges in the process of pooling MRI data recorded at various study centers in ALS. This approach is of utmost importance in order to establish MRI-based techniques as read-outs both fornatural history assessment and for potential upcoming disease-modifying multicenter studies in ALS ( Roßkopf et al., in press ). [ABSTRACT FROM AUTHOR]

Introduction Cognitive decline is a burdensome non-motor symptom in patients with Parkinson’s disease (PD). Functional MRI in the ’resting-state’ provides a valuable measure of intrinsic functional connectivity (iFC) between brain areas; alterations of iFC in PD have been demonstrated in several studies ( Prodoehl et al., 2014 ). However, these studies did not distinguish between cognitively unimpaired and impaired PD patients. This study aimed at investigating the iFC in PD depending on the patients’ cognitive status. Methods “Resting-state” fMRI (3 Tesla; BOLD-sensitive T2 ∗ -sequence) data were acquired in 14 cognitively unimpaired (PD-Cu) and 17 cognitively impaired PD patients (PD-CI) in comparison with 22 age-matched healthy controls. The classification of patients into subgroups (PD-Cu, PD-CI) was based on thorough neuropsychological testing according to recently proposed guidelines ( Litvan et al., 2012 ). The data analysis followed standardized procedures using the seed-based approach ( Gorges et al., 2014 ) in order to identify the default mode, frontoparietal control, visualspatial, the ventral and dorsal attention networks ( Smith et al., 2009 ). Results We observed significantly increased iFC (hyper-connectivity) in the sense of network expansions ( p < 0.0001; corrected for multiple comparisons) within the aforementioned networks in PD-Cu patients (vs. controls). The contrast of PD-CI vs. controls revealed significantly decreased iFC (hypo-connectivity) preferentially in areas associated with the default mode network, i.e. the hippocampus and between the long-distance midline cores (posterior cingulate cortex–medial prefrontal cortex). Conclusions In PD patients confirmed to be free of cognitive deficits, we demonstrated pronounced alterations of iFC as marked network expansions in the sense of recruiting additional resources as an adaptive (compensatory) mechanism in the progressive pathological process in PD. The cognitive reserve appears to be exhausted in the advanced stages of the disease due to increasing neuronal cell loss, resulting in functional disruption predominantly in cognition-associated brain areas. [ABSTRACT FROM AUTHOR]

Introduction In Huntington’s disease (HD), cerebral white matter changes have been reported in a number of studies using diffusion tensor imaging (DTI) or T1-weighted magnetic resonance imaging (MRI). A key question is how brain structure changes (both grey and white matter) influence brain function. Intrinsic functional connectivity (ifc) MRI investigates intrinsic connectivity networks (ICN), i.e. large-scale distributed functionally coupled brain regions observed in the absence of a specific task. The objective of our study was to integrate structural connectivity data as assessed by DTI with ifcMRI changes in order to obtain a comprehensive picture of structural and functional changes with an emphasis on motor and basal ganglia thalamic networks. Methods Thirty-five early HD subjects (TFC stage 1 and 2) and 32 age- and sex-matched healthy controls underwent3T-MRI (T1w, DTI and ifcMRI sequences). DTI and ifcMRI data analyses were performed using the Tensor Imaging and Fiber Tracking (TIFT) software ( Müller et al., 2007 ) for complementary DTI fiber tracking (FT) and ifcMRI data analysis. For the motor ICN ifcMRI analyses, the dominant M1 was used as the seed, for the basal ganglia-thalamic ICN the thalamus was used. In addition, the cortico-spinal tract (CST) and the thalamocortical pathway were used for comparisons at the group level. Results Structural connectivity measured by DTI at the group level showed an increase of FA values in the basal ganglia as well as FA reductions in the external and internal capsule, in parts of the thalamus, and in subcortical white matter. Intrinsic functional connectivity (brain function) showed hyper-connectivity in the motor ICN, i.e. the insula was less connected in HD than in controls. The basal ganglia-thalamic ICN connectivity differed between HD and controls in the insula and the basal ganglia in both hemispheres. Conclusion At the group level, we confirmed microstructural changes identified in previous DTI studies in HD (e.g. ( Rosas et al., 2006 )). There is evidence that the insula becomes disconnected from the motor cortex. The caudatum seems to lose its functional integration with widely distributed cortical areas (basal ganglio-thalamic ICN). Abnormal connectivity of the insula and caudatum may be relevant in the emergence of clinical signs of HD. Acknowledgements This work was partially supported by the European Union under the Seventh Framework programme - PADDINGTON Project, Grant Agreement No.261358, and the European Huntington’s Disease Network (EHDN), project 070 - PADDINGTON. [ABSTRACT FROM AUTHOR]

BackgroundDepressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.MethodWe compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).ResultsFrequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions.ConclusionsCurrent subthreshold depressive symptoms in early HD are associated with microstructural changes – without concomitant brain volume loss – in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology. [ABSTRACT FROM AUTHOR]

Actinobacillus actinomycetemcomitans has been implicated in the pathogenesis of several forms of early onset and refractory adult periodontitis. Early diagnosis of colonization of the oral cavity might be of importance in order to initiate preventive measures. The aim of the present study was to determine the potential diagnostic value of oral mucosal and salivary tests to identify. among healthy young men with no or minor periodontal disease, individuals colonized by A. actinomycetemcomitans. Two hundred and one male recruits, 18-25 yr of age, took part in the present study. Mean values of periodontal parameters suggested only minor periodontal disease. Of the sites, 64.8±17.6% (mean ± SD) had a periodontal probing depth (PPD) of 1 or 2 mm, only 1.6±2.9% deep sites of ≥5 mm were detected. More than 1000 subgingival and extracrevicular samples were selectively cultivated for A. actinomycetemcomitans. The organism was isolated in 55 subjects (27%). The odds for presence of at least 1 deep site of 5 mm was increased by a factor 1.99 if A. actinomycetemcomitans could be recovered. In identifying subjects colonized by A. actinomycetemcomitans, diagnostic test parameters sensitivity and predictive value for a negative test were 74.5±5.9% and 91.1±2.3%, respectively, for both saliva and dorsum of tongue samples. In contrast, pooled subgingival plaque from mesial surfaces of 1st molars was only 34.5±6.4% sensitive; the negative predictive value was 80.2±3.0%. The results point to a high diagnostic value of oral mucosal and especially saliva samples to identify young adult individuals colonized by A. actinomycetemcomitans. [ABSTRACT FROM AUTHOR]

Background A common feature of Parkinsonism – including idiopathic Parkinson’s disease (PD), Multisystem Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) – are characteristic alterations of eye movement control ( Gorges et al., 2014 ). Regional microstructural alterations assessed by diffusion tensor imaging (DTI) have been reported in PD ( Agosta et al., 2014 ), MSA ( Prakash et al., 2009 ) and PSP ( Rosskopf et al., 2015 ). Objective To investigate the association between eye movement disturbances and microstructural impairment in patients with PD, MSA and PSP. Methods Video-oculographic recordings (EyeSeeCam®) of smooth pursuit and visually guided reactive saccades as well as whole-brain based fractional anisotropy (FA) maps computed from diffusion tensor imaging (1.5T) data were analyzed for 37 IPS, 31 PSP, 19 MSA and 36 matched healthy control subjects. Results The prevalence of saccadic intrusions as a measure for inhibitory control was significantly increased in PD patients compared with controls ( p < 0.001) and negatively correlated with the fractional anisotropy (FA) in the capsula interna ( p < 0.001, FDR corrected). As a cardinal oculomotor feature in MSA, smooth pursuit was disturbed by characteristic ‘catch-up’ saccades ( p < 0.001) and was significantly correlated with a FA reduction in the middle cerebral peduncle ( p < 0.001, FDR corrected). The hallmark of PSP are pathologically slowed vertical peak eye velocities compared with controls ( p < 0.001); the lower the peak eye velocity the more marked microstructural impairment in midbrain ( p < 0.001, FDR corrected). Conclusions Eye movements alterations are predominantly the result of executive dysfunction in PD and reflect impaired infratentorial oculomotor control pathways in MSA and PSP. The worse the performance of the characteristic oculomotor parameter the more impaired was the associated regional microstructure. [ABSTRACT FROM AUTHOR]

Background Characteristically impaired oculomotor functions are recognized in Parkinsonian syndromes including idiopathic Parkinson disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) ( Pinkhardt and Kassubek, 2011 ). Atrophy of specific brain structures has been reported in Parkinsonian syndromes ( Brenneis et al., 2007; Focke et al., 2011 ). The aim of this study was to investigate possible relationships between oculomotor alterations and volumetric alterations in PD, PSP and MSA. Methods Forty-two PD, 18 MSA, and 32 PSP patients together with 26 healthy controls underwent standardized video-oculographic testing and MRI at a clinical 1.5T scanner. Whole-brain based T1-weighted MRI-images were analyzed using atlas-based volumetry ( Kassubek et al., 2011 ). Data of 5 brain structures (forebrain, brainstem, cerebellum, midbrain, pons) and 5 oculomotor parameters (smooth pursuit gain, peak eye velocity, rate of saccadic intrusions, anti-saccade errors) were used for group comparisons in PD, MSA and PSP with healthy controls. Oculomotor parameters were correlated with regional brain volumes in the patients. Results PD patients compared with control showed a significantly increased rate of saccadic intrusions (p). Conclusions The worse the oculomotor performance the lower the regional brain volume, suggesting a relationship between regional brain atrophy and cerebral oculomotor network disturbances. Deficits in eye movement control in PD appear to be characterized by executive abnormalities, whereas oculomotor dysfunctions in MSA and PSP were associated with impaired pontine and midbrain pathways. [ABSTRACT FROM AUTHOR]

Background Autopsy-controlled studies in Amyotrophic lateral sclerosis (ALS) proposed a 4-stage sequential spreading of the underlying TDP-43 pathology ( Brettschneider et al., 2013 ). Recently the in vivo transfer of the neuropathological stages by use of tract of interest-based diffusion-tensor-imaging (DTI) has been performed ( Kassubek et al., 2014 ). Based upon the DTI findings, we have expanded the imaging approach by complementary investigation of ifc-fMRI in order to trace the pathology spreading in well-defined intrinsic functional connectivity networks (ICNs). Methods We used a 3.0T resting state-fMRI protocol for 76 ALS patients and 28 healthy controls. The preprocessing followed standardized procedures including motion correction, MNI normalization, spatial filtering, temporal linear detrending and bandpass filtering. ICNs were identified utilizing the seed-based approach ( Gorges et al., 2014 ). These ICNs comprised the motor (neuropathological stage 1), frontoparietal, frontal executive and brainstem (stage 2), basal ganglia (stage 3), and hippocampal (stage 4) networks; we used the visual ICN as reference. Results ALS patients compared with healthy controls demonstrated a large-scale pattern of increased functional connectivity (hyperconnectivity) in all networks with the exception of the reference network. More specifically, the hyperconnectivity pattern extended spatially into adjacent brain structures following the neuropathological spreading. The hyperconnectivity in stage 1 extended into frontal areas, in stage 2 into prefrontal and postcentral areas, in stage 3 into prefrontal and postcentral areas, and in stage 4 within the hippocampal formation. Moreover, the disease stages as observed in vivo by DTI significantly correlated with increasing functional connectivity in the ICNs. Conclusion Ifc-fMRI provides a promising approach to functionally trace pathological spreading in ALS. As recently suggested ( Douaud et al., 2011 ), the loss of the inhibitory influence may be most likely attributable to the pattern of hyperconnectivity in ALS. With increasing stages of disease, hyperconnectivity seems to spread sequentially into more frontal and postcentral regions following the neuropathological spreading. [ABSTRACT FROM AUTHOR]

Abstract: Developmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming – among others – that dyslexia might be a disconnection syndrome of anterior and posterior brain regions involved in phonological and orthographic aspects of the reading process, as well as in the integration of phonemes and graphemes. Therefore, diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) were used to verify the hypothesis of altered white and gray matter structure in German dyslexic adults. DTI revealed decreased fractional anisotropy (FA) in bilateral fronto-temporal and left temporo-parietal white matter regions (inferior and superior longitudinal fasciculus). Significant correlations between white matter anisotropy and speed of pseudoword reading were found. In dyslexics, gray matter volumes (as measured by VBM) were reduced in the superior temporal gyrus of both hemispheres. So far, our results, based on a combined analysis of white and gray matter abnormalities, provide exceedingly strong evidence for a disconnection syndrome or dysfunction of cortical areas relevant for reading and spelling. Thus, we suggest that this imbalance of neuronal communication between the respective brain areas might be the crucial point for the development of dyslexia. [Copyright &y& Elsevier]

Objective In-vivo assessment of ALS-associated white matter alteration patterns by diffusion tensor imaging (DTI)-based metrics have been included in the NiSALS neuroimaging concept (Turner et al., LancetNeurol 2011). The objective of this multicenter study was to assess structural connectivity in ALS at a large sample-size. Methods Four-hundred-and-seven DTI data sets from patients with ALS ( N = 239) and controls ( N = 168) were collected from 8 international centers with different scanner systems and different DTI-protocols. Comparability of data with the aim of pooling was tested and differences were regressed out. Results Beyond patterns of alterations in the corticospinal tracts, whole brain-based statistical analysis, after pooling of data sets from all centers, additionally captured significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions, in keeping with the DTI-based correlates of post mortem neuropathological ALS-stages 1–4 (Kassubek et al., Brain 2014). Conclusion This study using an unprecedented number of subjects has detected more wide spread changes than typical single-site studies.The observed pattern of fiber tract pathology has the potential to serve as a biomarker of disease and progression and as a read-out for future clinical trials. Key message By this multi-centre approach, it was possible to non-invasively confirm the pathoanatomy of ALS in vivo . [ABSTRACT FROM AUTHOR]