Institute of Neuroscience and Medicine INM 2


Institute of Neuroscience and Medicine INM 2

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Hoffstaedter F.,RWTH Aachen | Hoffstaedter F.,Institute of Neuroscience and Medicine INM 2 | Sarlon J.,RWTH Aachen | Grefkes C.,Max Planck Institute for Neurological Research | And 4 more authors.
Behavioural Brain Research | Year: 2012

Background: Psychomotor retardation is a prominent clinical feature of major depression. While several studies investigated these deficits, differences between internally and externally triggered response selection and initiation are less well understood. In the current study, we delineate internally vs. externally driven response selection and initiation in depression and their relation to basic psychomotor functioning. Methods: 20 inpatients diagnosed with a (unipolar) major depression and 20 closely matched healthy controls performed a computerized motor paradigm assessing differences between internally and externally cued movements. Psychomotor performance and basic memory functions were assessed using a neuropsychological test-battery. To examine within group homogeneity a multivariate clustering approach was applied. Results: Patients featured a global slowing of internally and externally cued response selection compared to controls, as well as impairments in basic psychomotor functioning. Yet, basic motor speed was preserved. Furthermore, patients were more severely impaired when movements involved internal response selection. The data-driven clustering revealed two patient subgroups, which both showed psychomotor disturbances, while only one featured slowing of response selection. Interpretation: The results suggest a differential rather than a global psychomotor slowing in major depression with specific impairments of visuospatial and attentional processing as cognitive aspects of psychomotor functioning. As found for depression, in Parkinson's disease internally cued movements are more severely affected than externally cued reactions. Both may therefore be caused by dopaminergic deregulation due to frontostriatal deficits. Finally, multivariate clustering of behavioral data may be a promising future approach to identify subtypes of psychomotor or cognitive disturbances in different patient populations. © 2011 Elsevier B.V..

Noreik M.,University of Cologne | Kuhn J.,University of Cologne | Hardenacke K.,University of Cologne | Lenartz D.,University of Cologne | And 11 more authors.
Journal of Nutrition, Health and Aging | Year: 2015

Objective: The progression of Alzheimer’s disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson’s disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. Design: A 1-year phase I proof-of-concept study. Setting: The Department of Psychiatry and Psychotherapy at the University of Cologne. Participants: We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. Intervention: Bilateral low-frequency DBS of the nucleus basalis of Meynert. Measurements: Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. Results: With a normal body mass index (BMI) at baseline (mean 23.75 kg/m2) and after 1 year (mean 24.59 kg/m2), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = −0.829, p = 0.042). Conclusion: Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies. © 2015, Serdi and Springer-Verlag France.

Rehme A.K.,Max Planck Institute for Neurological Research | Rehme A.K.,University of Cologne | Rehme A.K.,Institute of Neuroscience and Medicine INM 2 | Volz L.J.,Max Planck Institute for Neurological Research | And 11 more authors.
Cerebral Cortex | Year: 2015

Conventional mass-univariate analyses have been previously used to test for group differences in neural signals. However, machine learning algorithms represent a multivariate decoding approach that may help to identify neuroimaging patterns associated with functional impairment in "individual" patients. We investigated whether fMRI allows classification of individual motor impairment after stroke using support vector machines (SVMs). Forty acute stroke patients and 20 control subjects underwent resting-state fMRI. Half of the patients showed significant impairment in hand motor function. Resting-state connectivity was computed by means of whole-brain correlations of seed time-courses in ipsilesional primary motor cortex (M1). Lesion location was identified using diffusion-weighted images. These features were used for linear SVM classification of unseen patients with respect to motor impairment. SVM results were compared with conventional mass-univariate analyses. Resting-state connectivity classified patients with hand motor deficits compared with controls and nonimpaired patients with 82.6-87.6% accuracy. Classification was driven by reduced interhemispheric M1 connectivity and enhanced connectivity between ipsilesional M1 and premotor areas. In contrast, lesion location provided only 50% sensitivity to classify impaired patients. Hence, resting-state fMRI reflects behavioral deficits more accurately than structural MRI. In conclusion, multivariate fMRI analyses offer the potential to serve as markers for endophenotypes of functional impairment. © The Author 2014. Published by Oxford University Press. All rights reserved.

Boaru S.G.,RWTH Aachen | Merle U.,University of Heidelberg | Uerlings R.,RWTH Aachen | Zimmermann A.,Central Institute of Engineering | And 4 more authors.
BMC Neuroscience | Year: 2014

Background: Neuropsychiatric affection involving extrapyramidal symptoms is a frequent component of Wilson's disease (WD). WD is caused by a genetic defect of the copper (Cu) efflux pump ATPase7B. Mouse strains with natural or engineered transgenic defects of the Atp7b gene have served as model of WD. These show a gradual accumulation and concentration of Cu in liver, kidneys, and brain. However, still little is known about the regional distribution of Cu inside the brain, its influence on other metals and subsequent pathophysiological mechanisms. We have applied laser ablation inductively coupled plasma mass spectrometry and performed comparative metal bio-imaging in brain sections of wild type and Atp7b null mice in the age range of 11-24 months. Messenger RNA and protein expression of a panel of inflammatory markers were assessed using RT-PCR and Western blots of brain homogenates. Results: We could confirm Cu accumulation in brain parenchyma by a factor of two in WD (5.5 μg g-1 in the cortex) vs. controls (2.7 μg g-1) that was already fully established at 11 months. In the periventricular regions (PVR) known as structures of prominent Cu content, Cu was reduced in turn by a factor of 3. This corroborates the view of the PVR as efflux compartments with active transport of Cu into the cerebrospinal fluid. Furthermore, the gradient of Cu increasing downstream the PVR was relieved. Otherwise the architecture of Cu distribution was essentially maintained. Zinc (Zn) was increased by up to 40% especially in regions of high Cu but not in typical Zn accumulator regions, a side effect due to the fact that Zn is to some degree a substrate of Cu-ATPases. The concentrations of iron (Fe) and manganese (Mn) were constant throughout all regions assessed. Inflammatory markers TNF-α, TIMP-1 and the capillary proliferation marker α-SMA were increased by a factor of 2-3 in WD. Conclusions: This study confirmed stable cerebral Cu accumulation in parenchyma and discovered reduced Cu in cerebrospinal fluid in Atp7b null mice underlining the diagnostic value of micro-local analytical techniques. © 2014 Boaru et al.; licensee BioMed Central Ltd.

Fischer T.,TU Dresden | Fischer T.,RWTH Aachen | Langner R.,RWTH Aachen | Langner R.,Institute of Neuroscience and Medicine INM 2 | And 4 more authors.
PLoS ONE | Year: 2010

In the electroencephalogram (EEG), early anticipatory processes are accompanied by a slow negative potential, the initial contingent negative variation (iCNV), occurring between 500 and 1500 ms after cue onset over prefrontal cortical regions in tasks with cue-target intervals of about 3 s or longer. However, the temporal sequence of the distributed cortical activity contributing to iCNV generation remains unclear. During iCNV generation, selectively enhanced low-beta activity has been reported. Here we studied the temporal order of activation foci in cortical regions assumed to underlie iCNV generation using source reconstruction of low-beta (13-18 Hz) activity. During the iCNV, elicited by a cued simple reaction-time task, low-beta power peaked first (750 ms after cue onset) in anterior frontal and limbic regions and last (140 ms later) in posterior areas. This activity occurred 3300 ms before target onset and provides evidence for the temporally ordered involvement of both cognitive-control and motor-preparation processes already at early stages during the preparation for speeded action. © 2010 Fischer et al.

Konrad K.,RWTH Aachen | Konrad K.,Institute of Neuroscience and Medicine INM 2 | Eickhoff S.B.,Institute of Neuroscience and Medicine INM 2 | Eickhoff S.B.,RWTH Aachen
Human Brain Mapping | Year: 2010

In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD. © 2010 Wiley-Liss, Inc.

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