The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity

This work was supported by a grant of the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, Grant Number EXC 1086).Peer reviewedPostprintPostprin

Functional compensation of motor function in pre-symptomatic Huntington's disease

Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of retained motor function in the presence of degenerative change. Fifteen pre-symptomatic gene carriers and 12 matched controls performed button presses paced by a metronome at either 0.5 or 2 Hz with four fingers of the right hand whilst being scanned with functional magnetic resonance imaging. Subjects pressed buttons either in the order of a previously learnt 10-item finger sequence, from left to right, or kept still. Error rates ranged from 2% to 7% in the pre-symptomatic gene carriers and from 0.5% to 4% in controls, depending on the condition. No significant difference in task performance was found between groups for any of the conditions. Activations in the supplementary motor area (SMA) and superior parietal lobe differed with gene status. Compared with healthy controls, gene carriers showed greater activations of left caudal SMA with all movement conditions. Activations correlated with increasing speed of movement were greater the closer the gene carriers were to estimated clinical diagnosis, defined by the onset of unequivocal motor signs. Activations associated with increased movement complexity (i.e. with the pre-learnt 10-item sequence) decreased in the rostral SMA with nearing diagnostic onset. The left superior parietal lobe showed reduced activation with increased movement complexity in gene carriers compared with controls, and in the right superior parietal lobe showed greater activations with all but the most demanding movements. We identified a complex pattern of motor compensation in pre-symptomatic gene carriers. The results show that preclinical compensation goes beyond a simple shift of activity from premotor to parietal regions involving multiple compensatory mechanisms in executive and cognitive motor areas. Critically, the pattern of motor compensation is flexible depending on the actual task demands on motor contro

Der Einfluß der Änderung der Schalenleitfähigkeit bei Randelementemodellen auf die Vorwärtsrechnung und das inverse Problem in Elektroenzephalographie und Magnetoenzephalographie

Source localization based on magnetoencephalographic and electroencephalographic data requires knowledge of the conductivitiy values of the head. The aim of this paper is to examine the influence of compartment conductivity changes on the neuromagnetic field and the electric scalp Potential for the widely used three compartment boundary element models. Both the analysis of measurement data and the simulations with dipoles distributed in the brain produced two significant results. First, we found the electric potentials to be approximately one order of magnitude more sensitive to conductivity changes than the magnetic fields. This was valid for the field and Potential topology (and hence dipole localization), and for the amplitude (and hence dipole strength). Second, changes in brain compartment conductivity yield the lowest change in the electric potentials topology (and hence dipole localization), but a very strong change in the amplitude (and hence in the dipole strength). We conclude that for the magnetic field the influence of compartment conductivity changes is not important in terms of dipole localization and strength estimation. For the electric potentials however, both dipole localization and strength estimation are significantly influenced by the compartment conductivity.Die Gewebeleitfähigkeitswerte des Kopfes sind für Quellerdokalisationen, basierend auf magnetoenzephalographischen und elektroenzephalographischen Daten, erforderlich. Das Ziel dieser Arbeit besteht darin, den Einfluß von Leitfähigkeitsänderungen auf das neuromagnetische Feld und die elektrische Potentialverteilung auf der Kopfoberfläche für die weitverbreiteten 3-Schalen-Randelementemodelle zu untersuchen. Sowohl die Analyse von Meßdaten als auch die Simulationen mit im Gehirn verteilten Einzeldipolen führten zu zwei wesentlichen Ergebnissen. Erstens war die Empfindlichkeit gegenüber Leitfähigkeitsänderungen beim elektrischen Potential ungefähr eine Größenordnung höher als beim magnetischen Feld. Dies galt sowohl für die Topologie (und damit für die Dipollokalisation) als auch für die Amplitude (und damit für die Dipolstärke). Zweitens zeigten Leitfähigkeitsänderungen der innersten Schale (Gehirn) die geringsten Änderungen in der Topologie des elektrischen Potentials (und damit in der Dipollokalisation), aber dabei eine sehr starke Änderung in der Amplitude (und damit in der Dipolstärke). Es kann geschlußfolgert werden, daß der Einfluß der Leitfähigkeitsänderung auf die Dipollokalisation und die Bestimmung der Dipolstärke aus dem magnetischen Feld vernachlässigt werden kann. Die Berechnung von Dipolort und -stärke aus dem elektrischen Potential ist jedoch signifikant von der Leitfähigkeit der Schalen abhängig

Postural control deficits due to bilateral pyramidal tract lesions exemplified by hereditary spastic paraplegia (HSP) originate from increased feedback time delay and reduced long-term error corrections

Pyramidal tract lesions determine the clinical syndrome of Hereditary Spastic Paraplegia (HSP). The clinical impairments of HSP are typically exemplified by their deficits in mobility, leading to falls and injuries. The first aim of this study was to identify the cause for postural abnormalities caused by pyramidal tract lesions in HSP. The second aim was to specify the effect of treadmill training for postural abnormalities. We examined nine HSP patients before and after treadmill training, as well as nine healthy control subjects during perturbed and unperturbed stance. We found that HSP was associated with larger sway amplitudes and velocities. Body excursions following platform tilts were larger, and upper body excursions showed a phase lead. Model-based analysis detected a greater time delay and a reduced long-term error correction of postural reactions in the center of mass. HSP patients performed significantly better in clinical assessments after treadmill training. In addition, treadmill training reduced sway amplitudes and body excursions, most likely by increasing positional and velocity error correction gain as a compensatory mechanism, while the time delay and long-term error correction gain remained largely unaffected. Moreover, the upper body’s phase lead was reduced. We conclude that HSP leads to very specific postural impairments. While postural control generally benefits from treadmill training, the effect seems to mainly rely on compensatory mechanisms, whereas the original deficits are not affected significantly

The rostro-caudal gradient in the prefrontal cortex and its modulation by subthalamic deep brain stimulation in Parkinson’s disease

Acknowledgements The authors thank Benjamin Rahm (University of Freiburg) and Michael Fox (Harvard Medical School) for valuable comments on a previous version of this manuscript. This work was supported by a grant of the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, grant number EXC 1086) to C.P.K., F.A., T.P., B.O.S., C.W, and V.A.C.; A.H. was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, Emmy Noether Stipend 410169619 and 424778381 – TRR 295) as well as Deutsches Zentrum für Luft- und Raumfahrt (DynaSti grant within the EU Joint Programme Neurodegenerative Disease Research, JPND). Funding Open Access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

Are old-old patients with major depression more likely to relapse than young-old patients during continuation treatment with escitalopram?

<p>Abstract</p> <p>Background</p> <p>Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD). This <it>post-hoc </it>analysis compared time to relapse for <it>young-old </it>patients (n = 197) to that for <it>old-old </it>patients (n = 108).</p> <p>Method</p> <p>Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12) were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (<it>old-old</it>) or 65-74 years of age (<it>young-old</it>), treated with escitalopram 10-20mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS).</p> <p>Results</p> <p>After open-label escitalopram treatment, a similar proportion of <it>young-old </it>patients (78%) and <it>old-old </it>patients (72%) achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression), with treatment and age group as covariates, the hazard ratio was 4.4 for placebo <it>versus </it>escitalopram (χ²-test, df = 1, χ²= 22.5, p < 0.001), whereas the effect of age was not significant, with a hazard ratio of 1.2 for <it>old-old </it>versus <it>young-old </it>(χ²-test, df = 1, χ²= 0.41, p = 0.520). Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of <it>young-old </it>patients and 58.3% of <it>old-old </it>patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ²-test, χ²= 1.669, df = 1, p = 0.196).</p> <p>Conclusions</p> <p><it>Young-old </it>and <it>old-old </it>patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.</p

The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study

<p>Abstract</p> <p>Background</p> <p>By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke.</p> <p>This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response.</p> <p>We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.</p> <p>Results</p> <p>As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01).</p> <p>Conclusions</p> <p>The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.</p

Stroke: Working Toward a Prioritized World Agenda

The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke

Stroke: Working Toward a Prioritized World Agenda

The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke