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ZusammenfassungDie überwiegende Anzahl bisheriger Studien zu Apraxien fokussiert die Rolle der linken Hemisphäre (LH), obwohl im klinischen Alltag apraktische Defizite auch bei Patienten mit rechtshemisphärischen Schlaganfällen (RH) beobachtet werden. Daher wurden in der aktuellen Untersuchung die Prävalenz und Ausprägung apraktischer Defizite bei Patienten mit linkshemisphärischen (n = 66) und rechtshemisphärischen (n = 73) Schlaganfällen verglichen, nachdem für Alter und sprachliche Leistung kontrolliert worden war.Unter Anwendung dieser Kontrollvariablen ergab sich kein signifikanter Unterschied zwischen den linkshemisphärisch und rechtshemisphärisch betroffenen Patienten bei der Imitation von Handpositionen. Übereinstimmend mit früheren Berichten schnitten die Patienten mit rechtshemisphärischen Schlaganfällen aber bei der Imitation der Fingerkonstellationen schlechter ab. Interessanterweise zeigten die rechtshemisphärisch betroffenen Patienten auch geringere Leistungen bei den bukkofazialen Items des Kölner Apraxie Screenings (KAS), vornehmlich bei Gesten der oberen Gesichtshälfte. Für beide Patientengruppen wirkten sich sprachliche Auffälligkeiten mehr auf die Pantomime- als auf die Imitationsleistungen beeinträchtigend aus.Die Ergebnisse legen nahe, dass nach der Kontrolle für Alter und sprachliche Leistungen die Prävalenz und Ausprägung apraktischer Defizite bei Patienten mit rechts- und linkshemisphärischen Schlaganfällen nicht signifikant unterschiedlich sind und in den jeweiligen Rehabilitationsprogrammen entsprechend berücksichtigt werden sollten.

Introduction. Transcranial direct current stimulation (tDCS) non-invasively modulates cortical function. We and others reported that tDCS could promote recovery after stroke (Braun et al., Exp. Neurol., 2016; Hummel et al., Brain, 2005). As a stroke affects entire networks, an aspect long neglected in translational research, we recently established a resting-state functional magnetic resonance imaging (rs-fMRI) protocol to detect similar network alterations in both rodent and human stroke (Blaschke et al., under review). We here investigated whether rs-fMRI can validate the efficacy of tDCS in altering functional connectivity after experimental stroke. Methods. Focal cortical stroke was induced via photothrombosis in male C57Bl/6J mice. Three days thereafter, cathodal tDCS over the lesioned sensory-motor cortex was applied for 15 minutes each day for ten days (charge density of 39600 C/m2). Longitudinal assessment of functional connectivity as measured by rs-fMRI was performed for up to 28 days post-stroke using a 9.4 T Bruker small animal scanner. Images were registered to the Allen Mouse Brain Atlas to derive seed regions for graph-based analysis and global graph parameters of network integration (characteristic path length, CPL) and segregation (clustering coefficient, CC) were computed over a sparse density range (10 – 30 % density), mimicking the brains“ functional structure. Additionally, a multiple linear regression was fitted to predict motor recovery based on initial network alteration, initial motor deficit, and tDCS treatment on motor recovery. Results. Ischemia induced an increase in connectivity. Already detectable three days after stroke, effects peaked at day 14, and spontaneously declined by day 28. Moreover, there was a significant reduction in characteristic path length (CPL) 14 days after stroke (p Conclusion. Stroke induces characteristic network changes that can be detected by rs-fMRI. Importantly, these network changes can, at least in part, be reversed by tDCS. Besides, the data suggest that early markers of network impairment improve the prediction of motor recovery. Overall, the data suggest that the characterization of functional connectivity by rs-fMRI is a powerful tool to analyze global changes after experimental stroke and to assess the therapeutic effects of non-invasive brain stimulation in preclinical studies.

Understanding how brain activity translates into behavior is a grand challenge in neuroscientific research. Simultaneous computational modeling of both measures offers to address this question. The extension of the dynamic causal modeling (DCM) framework for BOLD responses to behavior (bDCM) constitutes such a modeling approach. However, only very few studies have employed and evaluated bDCM, and its application has been restricted to binary behavioral responses, limiting more general statements about its validity.This study used bDCM to model reaction times in a spatial attention task, which involved two separate runs with either horizontal or vertical stimulus configurations. We recorded fMRI data and reaction times (n=29) and compared bDCM to classical DCM and a behavioral Rescorla-Wagner model using goodness of fit-statistics and machine learning methods.Data showed that bDCM performed equally well as classical DCM when modeling BOLD responses and better than the Rescorla Wagner model when modeling reaction times. Notably, only using bDCM’s parameters enabled classification of the horizontal and vertical runs suggesting that bDCM seems to be more sensitive than the other models. Although our data also revealed practical limitations of the current bDCM approach that warrant further investigation, we conclude that bDCM constitutes a promising method for investigating the link between brain activity and behavior.

BACKGROUND In light of increasing healthcare costs, higher medical expenses should be justified socio-economically. Therefore, we calculated the effectiveness and cost-effectiveness of PET using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) compared to conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recent study in IDH-wildtype glioma patients suggested that after two cycles, FET-PET parameter changes predicted a significantly longer survival while MRI changes were not significant. MATERIALS AND METHODS To determine the effectiveness and cost-effectiveness of serial FET-PET imaging, we analyzed published clinical data and calculated the associated costs in the context of the German healthcare system.Based on a decision-tree model, FET-PET and MRI’s effectiveness was calculated, i.e., the probability to correctly identify a responder as defined by an overall survival ≥15 months. To determine the cost-effectiveness, the incremental cost-effectiveness ratio (ICER) was calculated, i.e., the cost for each additionally identified responder by FET-PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic (Monte Carlo simulation) sensitivity analyses. RESULTS Compared to MRI, FET-PET increases the rate of correctly identified responders to chemotherapy by 26%; thus, four patients need to be examined by FET-PET to identify one additional responder. Considering the respective cost for serial FET-PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by FET-PET. The sensitivity analyses confirmed the robustness of the results. CONCLUSION In contrast to conventional MRI, the model suggests that FET PET is cost-effective in terms of ICER values. Concerning the high cost of temozolomide, the integration of FET-PET has the potential to avoid premature chemotherapy discontinuation at a reasonable cost.

Top-down focused spatial attention can counteract bottom-up attentional capture of an irrelevant but salient distractor outside the attentional focus. The present behavioural study differentiates two alternative concepts accounting for the absence of attentional capture under top-down focused attention. In particular, top-down focused attention may counteract attentional capture by altering salience coding outside the focus of attention. Alternatively, spatially focusing on a pre-defined region of potential target locations may omit the need to search among multiple salience signals, thereby eliminating the tendency of unattended stimuli to compete for attentional selection and, hence, to capture attention. Spatial cues explicitly indicating a variable number of potential target locations preceded the additional singleton paradigm to gradually manipulate the need to search for a target (i.e., to select a target from an array of distractors) and to determine its effects on attentional capture. Atte...

BACKGROUND Characterization of gliomas according to the revised World Health Organization (WHO) classification of 2016 has gained major importance regarding prognostication. The present study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed and molecularly defined astrocytic high-grade glioma (HGG) of the WHO grades III or IV. MATERIAL AND METHODS Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumor/brain ratios (TBRmax/mean), as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated with regard to the overall survival (OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess their predictive power for OS. RESULTS Sixty patients (45 GBM, 15 AA) of two university centers were retrospectively identified. Patients with a methylated MGMT promoter as well as with an IDH mutation had a significantly longer OS (both P25 minutes (AUC, 0.90; sensitivity, 90%; specificity, 87%; P CONCLUSION Data suggest that within the subgroup of patients with newly diagnosed and untreated IDH-wildtype GBM and AA, dynamic FET PET additionally allows the identification of patients with an improved OS.

BACKGROUND Following brain cancer treatment, the capacity of anatomical MRI to differentiate neoplastic tissue from treatment-related changes (e.g., pseudoprogression) is limited. This study compared apparent diffusion coefficients (ADC) obtained by diffusion-weighted MRI (DWI) with static and dynamic parameters of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation of treatment-related changes from tumor progression. MATERIAL AND METHODS Forty-eight pretreated high-grade glioma patients with anatomical MRI findings suspicious for progression (median time elapsed since last treatment, 16 weeks) were investigated using DWI and dynamic FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) as well as dynamic parameters (time-to-peak and slope values) of FET uptake were calculated. For mean ADC calculation, regions-of-interest analyses were performed on ADC maps calculated from DWI co-registered with the contrast-enhanced MR image. Diagnoses were confirmed neuropathologically (21%) or clinicoradiologically. Diagnostic performance was evaluated using receiver-operating-characteristic analyses or Fisher’s exact test for a combinational approach. RESULTS Ten of 48 patients had treatment-related changes (21%). The diagnostic performance of FET PET was significantly higher (threshold for both TBRmax and TBRmean, 1.95; accuracy, 83%; AUC, 0.89±0.05; P CONCLUSION Data suggest that static and dynamic FET PET provide valuable information concerning the differentiation of early treatment-related changes from tumor progression and outperform ADC measurement for this highly relevant clinical question.

ObjectiveTo investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.MethodsWe performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson’s Disease Rating Scale (UPDRS) (UPDRS-III “off” and “on” medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.ResultsPDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.ConclusionImpaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.Clinicaltrials.gov identifierNCT00354133.

The purpose of this study was to evaluate CatWalk's capability for assessing the functional outcome after photothrombotic stroke affecting the motor cortex of mice. Mice were tested up to 21 days after photothrombosis or sham surgery using CatWalk, and a composite score assessing functional deficits (neuroscore). The neuroscore demonstrated deficits of the contralateral forelimb for more than two weeks after stroke. There were no asymmetric or coordinative dysfunctions of limbs detected by CatWalk. However, CatWalk data revealed impairment of locomotion speed and its depending parameters for one-week after stroke in strong correlation to the neuroscore. Data suggest that the composite neuroscore allows to more sensitively and precisely specify and quantify photothrombosis-induced hemisyndromes than CatWalk.

Das Kolner Apraxie-Screening (KAS) erfasst apraktische Defizite nach linkshemispharischen Schlaganfallen. Ziel dieser Studie ist es, durch Anpassungen des Testmaterials des KAS und psychometrische Analysen ein diagnostisches Verfahren fur Patienten mit rechtshemispharischem Schlaganfall zu entwickeln. Mittels Itemanalysen von Daten 77 gesunder Probanden und 100 rechtshemispharischer Schlaganfallpatienten wurden 8 KAS-Items ausgeschlossen. Das somit noch aus 12 Items bestehende KAS-R weist eine gute interne Konsistenz (α = 0,795) sowie eine hohe Sensitivitat (79,4 %) und Spezifitat (84,4 %) auf. Bei einem Cut-off-Wert von ≤ 46 (von 48) Punkten zeigen 39 der 100 Schlaganfallpatienten eine Apraxie. Dabei korreliert das KAS-R – im Sinne einer guten Konstruktvaliditat – signifikant mit den externen Validierungsverfahren. Die Ergebnisse zeigen, dass das KAS-R ein reliables und valides diagnostisches Verfahren fur apraktische Defizite nach rechtshemispharischem Schlaganfall ist.

BACKGROUND: The aim of this study was to investigate the potential of combined radiomics textural feature analysis of contrast-enhanced MRI (CE-MRI) and static O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation of recurrent brain metastasis from radiation injury. MATERIAL AND METHODS: Fifty-two patients with newly diagnosed or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly radiosurgery, 84% of patients) of brain metastases were additionally investigated using FET PET. Based on histology (n=19) or clinicoradiological follow-up (n=33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two textural features were calculated on both unfiltered and filtered CE-MRI and summed FET PET images (20–40 min p.i). After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model. RESULTS: For differentiation between radiation injury and brain metastasis recurrence, textural features extracted from CE-MRI had a diagnostic accuracy of 81%. FET PET textural features revealed a slightly higher diagnostic accuracy of 83%. However, the highest diagnostic accuracy was obtained when combining CE-MRI and FET PET features (accuracy, 89%). CONCLUSION: Our findings suggest that combined FET PET/CE-MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases.

While visuo-spatial deficits are well characterized cognitive sequelae of right hemisphere (RH) stroke, apraxic deficits in RH stroke remain poorly understood. Likewise, very little is known about the association between apraxic and visuo-spatial deficits in RH stroke or about the putative common or differential pathophysiology underlying these deficits. Therefore, we examined the behavioral and lesion patterns of apraxic deficits (pantomime of object use and bucco-facial imitation) and visuo-spatial deficits (line bisection and letter cancellation tasks) in 50 sub-acute RH stroke patients. Using principal component analysis (PCA), we characterized the relationship between the two deficits. We hypothesized that any interaction of these neuropsychological measures may be influenced by the demands of ego-centric/space-based and/or allo-centric/object-based processing. Contra-lesional visuo-spatial deficits were common in our clinically representative patient sample, affecting more than half of RH stroke patients. Furthermore, about one third of all patients demonstrated apraxic deficits. PCA revealed that pantomiming and the imitation of bucco-facial gestures loaded clearly on a first component (PCA1), while letter cancellation loaded heavily on a second component (PCA2). For line bisection, overall mean deviation loaded on PCA1, while the difference between the mean deviations in contra- versus ipsi-lesional space loaded on PCA2. These results propose that PCA1 represents allo-centric/object-based processing and PCA2 2 ego-centric/space-based processing. This interpretation was corroborated by the statistical lesion analyses with the component scores. Data suggest that apraxic pantomime and imitation deficits in RH stroke result, at least in part, from disturbed allo-centric/object-based processing.

BACKGROUND In patients with glioblastoma, the tissue showing contrast enhancement (CE) in MRI is usually the target for resection or radiotherapy. However, the solid tumor mass typically extends beyond the area of CE. Amino acid PET can detect tumor parts that show no CE. We systematically investigated tumor volumes delineated by amino acid PET and MRI in newly diagnosed, untreated glioblastoma patients. MATERIAL AND METHODS Preoperatively, 50 patients with subsequently neuropathologically confirmed glioblastoma underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET, fluid-attenuated inversion recovery (FLAIR), and CE MRI. Areas of CE were manually delineated. FET PET tumor volumes were segmented using a tumor-to-brain ratio ≥ 1.6. The percentage of overlapping volumes (OV), as well as Dice and Jaccard spatial similarity coefficients (DSC; JSC), were calculated. FLAIR images were evaluated visually. RESULTS In 86% of patients (n = 43), the FET PET tumor volume was significantly larger than the volume of CE (21.5 ± 14.3 mL vs. 9.4 ± 11.3 mL; P < 0.001). Forty patients (80%) showed both an increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET and CE was low (mean DSC, 0.39 ± 0.21; mean JSC, 0.26 ± 0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In 10% of patients (n = 5), increased FET uptake was present outside of areas of FLAIR hyperintensity. CONCLUSION Our results show that the metabolically active tumor volume delineated by FET PET is significantly larger than tumor volume delineated by CE. The data strongly suggest that the information derived from FET PET should be integrated into the management of newly diagnosed glioblastoma patients. FUNDING This work was supported by the Wilhelm-Sander Stiftung, Germany

BACKGROUND A complete resection of high-grade gliomas (HGG) is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. We here evaluated the prognostic value of serial O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in patients with newly diagnosed, non-resectable astrocytic HGG undergoing chemoradiation with temozolomide. MATERIAL AND METHODS Serial dynamic FET PET scans were performed in 18 newly diagnosed patients with molecularly defined, non-resectable HGG at baseline and after chemoradiation (8±3 weeks). Both static (tumor/brain ratios, FET tumor volumes) and dynamic FET PET parameters (time-to-peak, slope), as well as MRI changes according to RANO criteria at first follow-up after chemoradiation (8±3 weeks), were obtained. The predictive ability of FET PET parameters and RANO criteria was evaluated with regard to the progression-free survival (PFS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate and multivariate survival analyses were performed to assess their predictive power for PFS. RESULTS ROC analysis revealed that the mean tumor/brain ratio (AUC, 0.84), FET tumor volume (AUC, 0.89), and slope (AUC, 0.72) at baseline were predictive for a prolonged PFS (9.3 vs. 5.7 months, P=0.05; 10.3 vs. 5.9 months; P=0.03; 13.5 vs. 6.2 months, P=0.02, respectively). Furthermore, FET tumor volume and slope remained significant in the multivariate survival analysis (both P CONCLUSION Results suggest that before initiation of chemoradiation FET PET parameters at baseline can be used to predict PFS in patients with non-resectable HGG.

BACKGROUND Radiomics derived from different imaging modalities is gaining increasing interest in the field of neuro-oncology. Besides MRI, amino acid PET radiomics may also improve the to date challenging, clinically relevant diagnostic problem of differentiating pseudoprogression (PsP) from tumor progression (TP). To this end, we here explored the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET radiomics to discriminate between PsP and TP. MATERIAL AND METHODS Thirty-five newly diagnosed IDH-wildtype glioblastoma patients with MRI findings suspicious for TP within 12 weeks after completion of chemoradiation with temozolomide underwent an additional dynamic FET PET scan. FET PET tumor volumes were segmented using a tumor-to-brain ratio (TBR) ≥ 1.6. The static PET parameters TBRmax and TBRmean, as well as the dynamic parameter time-to-peak (TTP), were calculated. For radiomics analysis, the number of datasets for model generation was increased using data augmentation techniques. Subsequently, 70 datasets were available for model generation. Prior to further processing, patients were randomly assigned to a discovery and a validation dataset in a ratio of 70/30, with balanced distribution of PsP and TP diagnoses. Forty-two radiomics features (4 shape-based, 6 first- and 32 second-order features) were obtained using the software LifeX (lifexsoft.org). Afterwards, a z-score transformation was performed for data normalization. For feature selection, recursive feature elimination using random forest regressors was performed. For the final model generation, the number of parameters was limited to three to avoid data overfitting. Different algorithms for model calculation were compared, and the diagnostic accuracy was assessed using leave-one-out cross-validation. Finally, the resulting models were applied to the validation dataset to evaluate model robustness. RESULTS Eighteen patients were diagnosed with TP, and 17 patients had PsP. Diagnoses were based on a neuropathological confirmation or clinicoradiological follow-up (26% and 74%, respectively). The diagnostic accuracy of the best single FET PET parameter was 75% (TBRmax). Combining TBRmax and TTP increased the diagnostic accuracy to 83%. Other combinations of static and dynamic FET PET parameters, however, did not further increase the accuracy. The highest diagnostic accuracy of 92% was achieved by a three-parameter model combining the FET PET parameter TTP with two radiomics features. The model demonstrated its robustness in the validation dataset with a diagnostic accuracy of 86%. CONCLUSION The results suggest that FET PET radiomics improves the diagnostic accuracy for discerning PsP and TP considerably. Given the clinical significance of differentiating PSP and TP, prospective multicenter studies are warranted. FUNDING Wilhelm-Sander Stiftung and the DAAD GERSS Program, Germany

Background: The phosphoglycoprotein osteopontin (OPN) is upregulated in the brain following cerebral ischemia, where is exerts neuroprotective properties. We previously demonstrated OPN to increase survival and proliferation of neural stem cells (NSC) in vitro and in vivo. In culture, OPN additionally promotes NSC migration as well as a neuronal differentiation fate. Based on these data, we hypothesized OPN to induce NSC migration as well as neurogenesis in vivo as well. We here aimed to establish and visualize these effects using non-invasive in vivo imaging. Methods: Transgenic mice expressing luciferase (luc) under the doublecortin (DCX) promoter were used for brain-specific bioluminescence imaging (BLI) of DCX + neuroblasts. Focal cerebral ischemia was induced via photothrombosis (PT) in n = 27 mice, while n = 16 mice served as healthy control (CNT). Mice were randomized to receive either OPN (n = 14 PT, n = 8 CNT), or saline (n = 13 PT, n = 8 CNT) via a single injection into the lateral ventricle of the brain. Magnetic resonance imaging (MRI) was performed to verify and localize infarcts. BLI data was repetitively obtained for a period of 28 days in each individual animal. Ex vivo, immunohistochemistry for DCX + neuroblasts served to validate imaging data at high resolution. Results: In both healthy as well as stroke mice treated with OPN intracerebroventricularly, we observed enhanced migration of DCX + neuroblasts towards the site of OPN injection over a period of 28 days, as assessed by BLI ( p 0.01 each). Moreover, the total flux of photons was increased in healthy mice 2 days after OPN injection, consistent with an expansion of neuroblasts numbers ( p 0.01 ). Under ischemic conditions, OPN increased neuroblast numbers as surrogate for neurogenesis throughout the observation period of 28 days, as assessed by BLI ( p 0.05 ). Conclusions: Data suggest positive effects of OPN on both the migration of neuroblasts as well as on neurogenesis in vivo. BLI visualizes and quantifies these effects non-invasively in the experimental animal in a longitudinal fashion, allowing to monitor the temporo-spatial dynamics of NSC mobilization under physiological conditions as well as in cerebral ischemia. The results confirm OPN as a promising drug to promote regeneration after stroke via its effects on neural stem cells.

Introduction Neuroimaging studies in stroke patients with hemiparesis have shown altered brain activation in the contralesional hemisphere including the primary motor cortex (M1), dorsal premotor cortex (dPMC) and anterior intraparietal sulcus (aIPS) already in the first week after stroke ( Rehme et al., 2011 ). The role of these regions for motor recovery is still under debate, with some studies suggesting a supportive influence ( Lotze et al., 2006 ) while other point to a maladaptive role ( Nowak et al., 2008 ). Especially functional reorganization in the early phase after stroke is not well understood, although this phase might be critical for non-invasive interventions aiming at supporting recovery of function ( Grefkes and Fink, 2016 ). We here used fMRI-guided online TMS applied over the contralesional M1, dPMC and aIPS of first-ever stroke patients with hand motor deficits in order to probe their role for movements of the paretic hand. Methods FMRI data were recorded from 13 patients 1–8 days after first-ever ischemic stroke and 14 age-matched healthy volunteers during index finger tapping in order to localize task-related activation in the contralesional hemisphere. Each subjects’ individual maxima in the contralesional M1, dPMC and aIPS were then used as targets to apply short trains of rTMS (10 Hz trains, 90% of rMT) time locked to task execution (online-TMS). Sham stimulation served as a control condition and was conducted at 90% of rMT, tilted over the parieto-occipital vertex in order to minimize interference with the motor system. Task performance was measured using a 3D motion analysis system. Imaging data were preprocessed and analyzed using SPM8 and the MarsBar toolbox. Results The severity of stroke as assessed by the NIHSS showed a positive correlation with the partients’ activation peaks in contralesional M1, indicating higher levels of activity in more affected patients. TMS application over the individual fMRI maxima led to differential effects on motor performance. In contralesional M1 and dPMC, TMS interference with local activity led to a normalization of kinematics in patients showing higher activation during paretic hand movements. This finding implies that early increases of neural activity in these regions after stroke rather represent a maladaptive process interfering with motor performance of the stroke-affected hand. In contrast, TMS-Effects with aIPS led to an increase of tapping amplitude and peak velocity across the patient group, thus normalizing performance. Conclusion The present study examined the role of contralesional M1, dPMC and aIPS activity for motor performance in early subacute stroke patients. While higher activation of M1 and dPMC in the first week after stroke were related to an improvement of motor fluency during online TMS interference, stimulation also of lower activation in contralesional aIPS led to a normalization of spatial aspects of motor performance. These findings suggest a disturbing influence of all examined regions on different features of movement kinematics already during the first days after stroke in mildly to moderately affected patients.

Background Event-related transcranial magnetic stimulation (TMS) allows to interfere with neural processing of cortical areas. While we have a rather good knowledge of the role of frontoparietal areas for motor performance of the contralateral hand, the contribution of ipsilateral areas is far less understood (Davare et al., 2007) . Neuroimaging studies found an increasing recruitment of ipsilateral motor regions in healthy elderly, implying a supportive influence during normative aging Hutchinson et al., 2002 , Riecker et al., 2006 . To test this hypothesis, we used online-TMS to investigate the role of ipsilateral primary motor cortex (M1), premotor cortex (dPMC), and the anterior intraparietal sulcus (aIPS) in motor tasks of different complexity in young and elderly subjects. Methods 30 healthy, right-handed subjects (15 young (27.8 y); 15 elderly (61.3 y)) conducted four motor tasks of different complexity: (i) simple reaction time task, (ii) maximum finger and (iii) hand tapping frequencies, and (iv) rapid pointing between two defined targets. Tapping and pointing tasks were recorded with kinematic motion analyzer system (Zebris). TMS pulses were applied as 10 Hz-trains, time-locked to task execution. Stimulation was applied at 90% intensity of the resting motor threshold (rMT) to ipsilateral M1, dPMC, and aIPS. Sham-stimulation at 90% of rMT to parieto-occipital vertex served as control condition. Results In the finger tapping task (ii) we found both a main effect of online-TMS and an interaction effect between group and stimulation site. While in elderly stimulation over dPMC led to a decrease in tapping intervall, performance in the young group was mainly affected by M1-stimulation. Furthermore, for the target pointing task (iv) we found a decrease of aiming accuracy in the elderly group upon TMS interference with aIPS and dPMC but the young stayed unaffected by stimulation over all sites. Finally, age correlated with a frequency reduction of hand tapping (iii) induced by aIPS-stimulation. Conclusion Our findings suggest that there are differential roles of investigated areas in motor performance in aging. The data further displays relevance of dPMC and aIPS in repetitive tapping and target pointing tasks in elderly. Both regions seem to be causally engaged in maintaining performance in elderly. This might indicate that an increasing recruitment of ipsilateral motor regions Hutchinson et al., 2002 , Riecker et al., 2006 seems to have a supportive influence on motor performance in elderly.

Cognitive impairment is a common and largely undiagnosed finding in a significant number of dialysis patients. These alterations may result from concomitant cerebrovascular disease, hemodynamic instability, the uremic milieu, or changes induced by the dialysis process. In order to gain further insight into this, we recruited 12 stable chronic hemodialysis patients (without clinical neurological disease) and an age- and gender-matched cohort of 12 control individuals (without renal or neurological problems) in a prospective, single-center study. In order to disentangle the influence of dialysis itself on memory function, each dialysis patient was tested twice: once immediately before dialysis following a long weekend (t1) and again the day after this dialysis (t2). The control individuals were tested in the same time frame. Neuropsychological testing found that the control individuals performed significantly better in verbal learning, motor speed, task switching, verbal comprehension, word fluency, spatial visualization, spatial perception, and reasoning; all independent of the time point. Functional magnetic resonance imaging of the whole brain in seven hemodialysis patients found significantly more bilateral activation of the hippocampus during the verbal working memory task at t2 relative to t1 compared with their seven matched control counterparts. Thus, our study found differential and task-specific activation of memory-relevant brain areas during a dialysis cycle.

In addition to motor symptoms, patients with Parkinson's disease (PD) show deficits in sensory processing. These deficits are thought to result from deficient gating of sensory information due to basal ganglia dysfunction in PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve sensory deficits in PD, e.g. STN-DBS normalizes the perception of urinary bladder filling in patients with PD. This study aimed at investigating how STN-DBS modulates the processing of urinary bladder information to elucidate the (patho-)physiology of sensory gating mechanisms in PD. Nine PD patients with bilateral STN-DBS switched on (STN-DBS ON) or off (STN-DBS OFF) were studied during dynamic bladder filling and an empty bladder condition (for control), while changes in regional cerebral blood flow (rCBF) were measured by PET. Urinary bladder filling led to an increased rCBF in the periaqueductal grey (PAG), the posterior thalamus, the insular cortex as well as in the right frontal cortex and the cerebellum bilaterally. A significant interaction between bladder condition and STN-DBS was observed in the posterior thalamus and the insular cortex, with enhanced modulation of these areas during STN-DBS ON compared to STN-DBS OFF. Furthermore, regression analyses revealed a modulation of the neural activity in the thalamus and the insular cortex by the PAG activity during STN-DBS ON only. Thus, STN-DBS led to a significant enhancement of afferent urinary bladder information processing. The data suggest that STN-DBS facilitates the discrimination of different bodily states by supporting sensory perception and the underlying neural mechanisms. Furthermore, this is the first imaging study, which shows an effect of STN-DBS on sensory gating in PD patients and its neural basis.

Research investigating risk perception suggests that not only the quantitative parameters used in technical risk assessment (i.e., frequency and severity of harm) but also 'qualitative' aspects such as the dread a hazard provokes or its controllability influence risk judgments. It remains to be elucidated, however, which neural mechanism underlie risk ratings in healthy subjects. Using fMRI to detect changes in neural activity we compared the neural activations elicited by risk ratings with those elicited by a letter detection task performed on the same stimuli. The latter task served to control for basic stimulus processing, response selection and button-pressing during task performance. Risk ratings differentially activated the medial prefrontal cortex, the inferior frontal gyrus, the cerebellum (P

The performance of motor actions is a highly complex task where the movement of different body parts has to be coordinated by the activity of various brain regions. In particular, the interplay of brain regions of the motor cortex is crucial. In the study presented here, the interaction of different motor related brain regions during simple internally and externally initiated finger movements was investigated during preparation and execution of those movements. To this end, EEG data (64 channel system) were recorded from 18 right-handed healthy participants (22–35 years, 10 female). The participants performed a finger tapping paradigm that contained left and right index finger movements which were triggered either by a visual cue or by voluntary choice. We carried out inter-regional phase-locking analysis of Morlet wavelet phases in delta-theta (2–7 Hz), alpha (8–12 Hz) and beta (13–30 Hz) frequency bands of the Laplacian referenced EEG data in order to identify coupling between brain regions during the motor task. We analyzed connectivity in a network involving electrodes lying above the premotor areas (PM: FC3, FC4), the supplementary motor areas (SMA: Cz, FCz) and the primary motor cortex (M1: C3, C4) as nodes. We found significant changes of synchronization in the delta-theta frequency band during both movement preparation and execution. The construction of lateralization networks revealed that the phase-locking effect in these frequency bands was stronger for connections from motor regions to supplementary motor areas contralaterally to the moving hand than on the ipsilateral side. The interregional synchronizations appeared only when both regions showed strong intraregional phase locking. Thus, intraregional phase locking in the delta-theta frequencies seems to be a prerequisite for interregional phase locking. We hypothesize that both intra- and interregional phase locking form a functional network of synchronous activity. This activity enhances the excitability of the motor system so that transient cue signals are able to induce different kinds of movements during movement preparation. Additionally we found strong synchronization in the beta-frequency band that appeared after the movement has been executed for connections from the supplementary motor areas to the primary motor cortex and the pre-motor cortex contralaterally to the moving hand. Since this synchronization effect is expressed significantly stronger during the self-initiated than during visually-triggered finger movements, we suggest that it might be related to the suppression of the internal “go” cue after the movement was executed.

Background Event-related (“online”) transcranial magnetic stimulation (TMS) allows to interfere with neural processing of distinct cortical areas. While we have a rather good knowledge on the role of frontoparietal areas for motor performance of the contralateral hand, the contribution of areas in the hemisphere ipsilateral to the moving hand is far less understood ( [Davare et al., 2007] , [Vollmer et al., 2015] ). For example, neuroimaging studies found an increasing ipsilateral recruitment of motor regions in healthy eldery subjects, implying a supportive influence during normative ageing ( [Hutchinson et al., 2002] , [Riecker et al., 2006] ). To test this hypothesis, we used online-TMS to investigate the role of ipsilateral primary motor cortex (M1), premotor cortex (dPMC) and anterior intraparietal sulcus (aIPS) in motor tasks of different complexity in young and elderly subjects. Methods Young (range: 20–30 years) and elderly (range: 50–70 years) healthy, right-handed subjects conducted four motor tasks of different complexity with their right hand: (i) simple reaction time, (ii) maximum finger and (iii) hand tapping frequencies and (iv) rapid pointing between two defined targets. Tapping and pointing tasks were measured with kinematic, three-dimensional recordings using an ultrasound motion analyzer system (Zebris). TMS pulses were applied as 10 Hz-trains time-locked to task execution. Stimulation was applied at 90% of resting motor threshold (rMT) to ipsilateral M1, dPMC and aIPS. Sham-stimulation at 90% of rMT to parieto-occipital vertex served as control condition. Results Online-TMS applied to ipsilateral M1 led to a significant response slowing and to a significantly increased coeffcient of variation in the simple reaction time task in elderly subjects. In contrast, performance of more complex motor tasks was not affected by ipsilateral M1-stimulation. TMS applied to the ipsilateral dPMC or aIPS affected the more complex motor tasks. DPMC-stimulation caused a reduction of tapping amplitude and a significant reduction of overall performance in the finger tapping task. TMS applied to the aIPS led to a significant reduction of tapping amplitude and tended to reduce overall performance in the hand tapping task. Furthermore, subjects showed a significant decrease of aiming accuracy in the pointing task, upon TMS interference with ipsilateral dPMC as well as aIPS in elderly subjects. Finally, within the group of elderly subjects, age strongly correlated with a frequency reduction of hand tapping induced by both M1- and aIPS-stimulation. Conclusion Consistent with previous work ( Vollmer et al., 2015 ), our findings underline the impact of ipsilateral M1 on simple motor task. We also show that in eldery subjects ipsilateral dPMC as well as ipsilateral aIPS seem to be causally engaged in maintaining performance in more complex motor tasks. These findings agree with neuroimaging studies indicating the IPS’ particular involvement in visuomotor tasks ( Grefkes et al., 2006 ). Of note, our results support the notion of age-dependent recruitment of ipsilateral M1 in motor tasks ( [Hutchinson et al., 2002] , [Riecker et al., 2006] ) and suggest a similar relevance of aIPS for motor performance in healthy ageing individuals.

Background/Objective Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and nucleus caudatus) modulates the inhibition of response impulses and thereby contributes to an important aspect of cognitive control. The present study aimed at further investigating the putative role of the striatum within the fronto-striatal network in cognitive control processes. Methods Twenty-three patients with unilateral lesions (caused by stroke) involving the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated, so that the efficacy of cognitive control processes can be inferred by the (prolonged) reaction times in situations when a response conflict has to be resolved. Results Stroke patients responded overall slower and more erroneous than controls. The difference in response times to incongruent versus congruent trials (known as the Simon effect) was reduced in the ipsilesional/-lateral hemifield, but did not differ significantly between groups in the current unimanual version of the Simon task. Discussion Thus, in stroke patients unilateral lesions of the striatum did not significantly impair cognitive control processes (here: control of response interference). Possible compensatory mechanisms and implications of these findings for theoretical accounts of the Simon effect are discussed.

Objective Whether processing of function knowledge about tools (i.e., knowing what a tool is used for) draws upon action or semantic knowledge remains controversial. Methods We investigated this issue using fMRI. 17 subjects performed three experimental tasks tapping into different aspects of tool knowledge. Data were analyzed using SPM and dynamic causal modeling (DCM). Results The behavioral data and fMRI activation pattern suggested that function knowledge about tools was processed similarly as non-motor-related semantic tool knowledge (here: the monetary value of a tool) and could therefore be classified as “motor-related semantic knowledge”, whereas action knowledge (i.e., how a tool is used) was processed differently. Processing of action knowledge activated areas of the ventro-dorsal stream (i.e., the lateral occipito-temporal cortex (LOTC) bilaterally, the left intraparietal sulcus (IPS), the left supramarginal gyrus (SMG), and the left inferior frontal gyrus (IFG)). In contrast, ventral stream areas were activated by the processing of semantic tool knowledge: the fusiform gyrus (FFG) bilaterally, the angular gyrus (ANG) bilaterally, and the medial prefrontal cortex (mPFC). Analyzing the effective connectivity between these areas with DCM revealed interactions between the processing streams (between LOTC and FFG as well as between SMG and ANG) and reciprocal modulatory effects. Conclusions This fMRI-study substantiates that action and semantic knowledge about tools are processed along two separate routes and that function knowledge (i.e., knowing what a tool is used for) draws upon the semantic system. In addition, connectivity analysis with DCM revealed relevant interactions between the processing streams at lower and higher levels.

Transcranial direct current stimulation (tDCS) has been suggested as an adjuvant tool to promote recovery of function after stroke, but the mechanisms of its action to date remain poorly understood. Moreover, studies aimed at unraveling those mechanisms have essentially been limited to the rat, where tDCS activates resident microglia as well as endogenous neural stem cells. Here we studied the effects of tDCS on microglia activation and neurogenesis in the mouse brain. Male wild-type mice were subjected to repetitive tDCS of either anodal or cathodal polarity; sham-stimulated mice served as control. Activated microglia in the cerebral cortex, and neuroblasts generated in the subventricular zone as the major neural stem cell niche, were assessed immunohistochemically. Repetitive tDCS at a sub-lesional charge density led to a polarity-dependent downregulation of the constitutive expression of Iba1 by microglia in the mouse cortex. In contrast, both anodal and – to an even greater extent – cathodal tDCS induced neurogenesis from the subventricular zone. Data suggest that tDCS elicits its action through multi-facetted mechanisms, including immunomodulation and neurogenesis, and thus support the idea of using tDCS to induce regeneration and to promote recovery of function. Furthermore, data suggest that the effects of tDCS may be animal- and polarity-specific.

Introduction Coordinated hand movements derive from fine-tuned interactions of various motor regions. Transcranial magnetic stimulation (TMS) allows to test the role of cortical motor areas. Disturbing the activity of the primary motor cortex (M1) ipsilateral to the moving hand via ‘online’ TMS, i.e., applied during task execution, has been shown to alter the recruitment of hand muscles in grip-lift-tasks ( Davare et al., 2007 ). Then again, similar stimulation had no effect on the performance of simple reaction-time tasks ( Nardone et al., 2013 ). Conflicting data might result from differences in stimulation parameters (e.g., stimulation intensity) or from motor task specific effect of online-TMS interference. We, here, applied online TMS to M1 while subjects performed motor-tasks of different complexities with the ipsilateral hand to further our insights into the exact role of the ipsilateral M1 in hand movement. Material and methods 16 healthy, right-handed subjects performed three different motor tasks with the right index finger (simple reaction-time and maximum finger-tapping task) or the right hand (maximum grip strength over one second). TMS Pulses were applied as 10 Hz-trains time-locked to motor task execution. Performance was measured for four different conditions. Real-stimulation was applied at three different intensities: (i) 70%, (ii) 80%, or (iii) 90% of the resting motor threshold (RMT) to the right M1. Sham-stimulation was applied at 90% RMT over parieto-occipital vertex. The order of stimulation blocks was pseudo-randomized across subjects. Results Online TMS applied to the right M1 differentially affected motor task performance with the right (ipsilateral) hand. Maximum finger-tapping frequency and the integrated grip strength time course were significantly reduced by real compared to sham stimulation. Of note, we found a stimulation intensity dependent effect with higher stimulation intensities leading to stronger reduction in motor performance. In contrast, performance in the simple reaction-time task was not affected by online TMS. Discussion We found online TMS applied to M1 to impact on the motor function of the ipsilateral hand. Importantly, the ‘virtual lesion’ effect induced by online TMS strongly depended on the intensity at which pulses were applied and the given motor task. Our results suggest M1 to functionally contribute to the repetitive and timely precise recruitment of ipsilateral hand muscles. Finally, our experimental approach also offers the opportunity to study the altered role of the ipsilateral M1 in disease, e.g., during motor network reorganization following stroke.

In patients with low-grade glioma (LGG) of World Health Organization (WHO) grade II, early detection of progression to WHO grade III or IV is of high clinical importance because the initiation of a specific treatment depends mainly on the WHO grade. In a significant number of patients with LGG, however, information on tumor activity and malignant progression cannot be obtained on the basis of clinical or conventional MR imaging findings only. We here investigated the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET to noninvasively detect malignant progression in patients with LGG.Twenty-seven patients (mean age ± SD, 44 ± 15 y) with histologically proven LGG (WHO grade II) were investigated longitudinally twice using dynamic (18)F-FET PET and routine MR imaging. Initially, MR imaging and PET scans were performed, and diagnosis was confirmed on the basis of biopsy. Subsequently, PET scans were obtained when clinical findings or contrast-enhanced MR imaging suggested malignant progression. Maximum and mean tumor-to-brain ratios (20-40 min after injection) (TBRmax and TBRmean, respectively) of (18)F-FET uptake as well as tracer uptake kinetics (i.e., time to peak [TTP] and patterns of the time-activity curves) were determined. The diagnostic accuracy of imaging parameters for the detection of malignant progression was evaluated by receiver-operating-characteristic analyses and by Fisher exact test for 2 × 2 contingency tables.In patients with histologically proven malignant progression toward WHO grade III or IV (n = 18), TBRmax and TBRmean increased significantly, compared with baseline (TBRmax, 3.8 ± 1.0 vs. 2.4 ± 1.0; TBRmean, 2.2 ± 0.3 vs. 1.6 ± 0.6; both P0.001), whereas TTP decreased significantly (median TTP, 35 vs. 23 min; P0.001). Furthermore, time-activity curve patterns changed significantly in 10 of 18 patients (P0.001). The combined analysis of (18)F-FET PET parameters (i.e., changes of TBRmax, TTP, or time-activity curve pattern) yielded a significantly higher diagnostic accuracy for the detection of malignant progression than changes of contrast enhancement in MR imaging (accuracy, 81% vs. 63%; P = 0.003).Both tumor-to-brain ratio and kinetic parameters of (18)F-FET PET uptake provide valuable diagnostic information for the noninvasive detection of malignant progression of LGG. Thus, repeated (18)F-FET PET may be helpful for further treatment decisions.

Jede akute neurologische Erkrankung (zerebrovaskulare Erkrankungen, Meningitis/Enzephalitis u. a.) kann sich vor oder wahrend einer Schwangerschaft manifestieren. In diesen Fallen muss immer eine sofortige neurologische Mitbehandlung erfolgen. Diese zahlreichen Erkrankungen sollen jedoch nicht Gegenstand dieses Kapitels sein. Im Fokus sollen vielmehr diejenigen haufigen, in der Regel chronischen neurologischen Erkrankungen stehen, die bei Frauen mit einem Kinderwunsch bzw. bei Frauen im konzeptionsfahigen Alter bestehen konnen. Dabei handelt es sich in erster Linie um Epilepsie, Multiple Sklerose und neuromuskulare Erkrankungen.

Introduction One of the key symptoms of Parkinson’s disease (PD) is the impairment of spontaneous movement also known as akinesia ( Berardelli et al., 2001 ). Correspondingly, patients performing motor tasks feature abnormal activation in regions such as posterior medial frontal cortex (pMFC) and putamen ( Herz et al., 2013 ). These areas play crucial roles in the internal timing of volitional movements in healthy individuals ( Hoffstaedter et al., 2013 ). Yet, little is known about these regions’ functional connectivity (FC) in PD and its relationship with akinesia. The present study investigated FC alterations of the ’motor initiation network’ in PD, using a seed-based resting-state (RS) analysis. Methods RS fMRI data of 60 patients diagnosed with idiopathic PD (mean age 61.6 ± 10.2; mean disease duration 6.5 ± 5.5 years) and 72 healthy volunteers (mean age 60.1 ± 8.8, matched for age, gender and within-scanner movement) was acquired at two sites. After spatial preprocessing (realignment, normalization, smoothing), temporal filtering was conducted including motion confound removal and band-pass filtering. Seeds in bilateral putamen and pMFC were derived from a meta-analysis on volitional movements ( Hoffstaedter et al., 2014 ). Two more seeds were selected in bilateral primary motor cortex (M1). For each seed, (i) whole-brain FC and (ii) its interaction with akinesia (UPDRS item 3.14) were assessed. RS networks for the aforementioned regions were first mapped in healthy controls only: Contrasting each region’s FC to the FC of all respective other seeds yielded maps of specific connectivity with either seed. These networks were then used to map whole-brain corrected changes of FC in PD. Results were cluster-level corrected for multiple comparisons ( p Results In healthy participants, RS analysis differentiated three networks, specifically (more than all other seeds) connected to bilateral putamen, bilateral M1, and pMFC. In PD, all seeds consistently featured decreased FC with regions in their most related network. That is, M1 mainly showed FC decrease within the M1-related network, pMFC lost FC with anterior insulae and left dorsolateral prefrontal cortex (DLPFC; pMFC-related network), and putamen lost FC with caudate nucleus, pallidum and thalamus (Putamen-related network). Additionally, putamen FC decreased extensively also in those regions more related to M1 and pMFC, including visual, superior parietal, primary somatosensory, M1, pMFC and DLPFC. Testing for each seed’s interaction with akinesia, pMFC showed a decreased FC with inferior parietal lobe (IPL) in the pMFC-related network. In turn, FC of the other seeds did not significantly relate to akinesia. Conclusions The present study examined RS FC changes of bilateral putamen, M1 and pMFC in PD. In patients, putamen FC suggests a marked cortico-striatal decoupling, in line with pathophysiological models of the disease ( Braak et al., 2004 ). In contrast, pMFC featured more selective FC decreases, predominantly in regions involved in motor control ( Hoffstaedter et al., 2013 , Hoffstaedter et al., 2014 ). Notably, akinesia was exclusively related to pMFC-connectivity. With increasing impairment, pMFC decoupled from the right IPL. In sum, the present study demonstrates a disruption of cortico-striatal FC and specifies the role of pMFC - IPL connectivity for movement initiation in PD.

Motor actions are generated by complex interactions of various brain regions. The same brain regions can build various functional networks depending on the action. Identifying the neural signals that encode an action’s component (selection, preparation, execution) remains a difficult task. In the current study, EEG data were recorded continuously from 18 young (22–35 years) and 16 elderly (60–71 years) right-handed healthy subjects as they performed a simple motor task. The task required participants to execute a left or right index finger tapping triggered by a visual cue or by an uncued voluntary choice. We found that voluntary and visually triggered movements exhibit significant phase locking in the delta-theta frequency band (2–7 Hz) around movement onset both in young and old subjects. However, significant differences in movement and processing time between the two groups of subjects were observed as well. Moreover, there was a negative correlation between the movement time and the maximal value of the phase-locking index (PLI) in young subjects. This indicates that the aforementioned changes in behavioral performance result from a decrease of PLI in the respective motor regions. In summary, we suggest that this enhanced intra-regional synchrony, which seems to be impaired in the elderly, helps the simultaneously active pathways of distinct cortical networks that initiate voluntary and stimulus-triggered movements, converge to a common motor output and activate the appropriate muscles to perform the movement. This mechanism may thus be regarded as a prototype for organizing more complex motor activities.