Rudolf Magnus Institute of Neuroscience

Utrecht, Netherlands

Rudolf Magnus Institute of Neuroscience

Utrecht, Netherlands
Time filter
Source Type

Kwakkel G.,VU University Amsterdam | Kwakkel G.,Rudolf Magnus Institute of Neuroscience | Kollen B.J.,University of Groningen
International Journal of Stroke | Year: 2013

Knowledge about factors that determine the final outcome after stroke is important for early stroke management, rehabilitation goals, and discharge planning. This narrative review provides an overview of current knowledge about the prediction of activities after stroke. We reviewed the pattern of stroke recovery for functions and activities, the impact of spontaneous recovery on activities, and the measurement of improvement in general. We explored the activities profiles during the chronic phase and predictors for activities of daily living independence after stroke, and finally, we discussed where to from here? Mathematical regularities explain the nonlinear patterns of recovery, making the outcome of activities of daily living highly predictable. Initial severity of disability and extent of improvement observed within the first weeks poststroke are important indicators of the outcome at six-months. The sequence of progress in activities is almost fixed in time. Studies showed that most motor recovery is almost completed within 10 weeks poststroke. On average, stroke recovery plateaus three- to six-months after onset. Strong evidence was found that age and scores on scales assessing severity of neurological deficits in the early poststroke phase are strongly associated with the final basic activities of daily living outcome after three-months poststroke. The validated prediction models using simple algorithms, such as National Institutes of Health Stroke Scale or Barthel Index, need to be implemented in rehabilitation services and used for stratifying stroke patients in trials. Future studies should investigate the accuracy of dynamic models that includes time poststroke to optimize the application of prediction rules in individuals with stroke. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Hermes D.,Rudolf Magnus Institute of Neuroscience | Siero J.C.W.,Rudolf Magnus Institute of Neuroscience | Aarnoutse E.J.,Rudolf Magnus Institute of Neuroscience | Leijten F.S.S.,Rudolf Magnus Institute of Neuroscience | And 3 more authors.
Journal of Neuroscience | Year: 2012

It is often assumed that similar behavior is generated by the same brain activity. However, this does not take into account the brain state or recent behavioral history and movement initiation or continuation may not be similarly generated in the brain. To study whether similar movements are generated by the same brain activity, we measured neuronal population activity during repeated movements. Three human subjects performed a motor repetition task in which they moved their hand at four different rates (0.3, 0.5, 1, and 2Hz). From high-resolution electrocorticography arrays implanted on motor and sensory cortex, high-frequency power (65-95 Hz) was extracted as a measure of neuronal population activity. During the two faster movement rates, high-frequency power was significantly suppressed, whereas movement parameters remained highly similar. This suppression was nonlinear: after the initial movement, neuronal population activity was reduced most strongly, and the data fit a model in which a fast decline rapidly converged to saturation. The amplitude of the beta-band suppression did not change with different rates. However, at the faster rates, beta power did not return to baseline between movements but remained suppressed. We take these findings to indicate that the extended beta suppression at the faster rates, which may suggest a release of inhibition in motor cortex, facilitates movement initiation. These results show that the relationship between behavior and neuronal activity is not consistent: recent movement influences the state of motor cortex and facilitates next movements by reducing the required level of neuronal activity. © 2012 the authors.

Laarakker M.C.,University Utrecht | Laarakker M.C.,Rudolf Magnus Institute of Neuroscience | van Lith H.A.,University Utrecht | Ohl F.,University Utrecht
Physiology and Behavior | Year: 2011

Up to 29% of all adults will experience an anxiety-related disorder during their lives. Treatment of these disorders is still difficult and the exact mechanisms and pathways behind anxiety disorders remain to be elucidated. Although evidence exists for genetically based susceptibility of human psychiatric diseases, risk genes have rarely been identified up to now. Inbred mouse strains are, together with the crosses and genetic reference populations derived from them, important tools for the genetic dissection of complex behavioral traits in the mouse. Thus, inbred mouse models of human anxiety may be a potent starting tool to search for candidate genes in mice, which could then via comparative genomics be translated to the human situation. In this paper we investigate whether the A/J and C57BL/6J mouse inbred strains differ in a limited number of motivational systems (anxiety, exploration, memory, locomotion, and social affinity), but especially in anxiety-related behavior from each other. Young adult individuals from both genders of A/J and C57BL/6J strains were behaviorally phenotyped using a multidimensional test: the modified hole board. This paradigm basically is a combination of the traditional hole board and the open field test allowing to test for anxiety-related avoidance behavior, risk assessment, arousal, exploration, memory, locomotor activity, and social affinity, using just one single test. An acute, aversive stimulus (intra-peritoneal injection with saline) was applied to the animals to test for the robustness of their behavioral phenotype. In addition, presumed physiological indicators for anxiety (circulating glucose, cholesterol, and corticosterone, adrenal tyrosine hydroxylase, and blood plasma and brain magnesium) were investigated. It could be concluded that C57BL/6J and A/J mice differ with respect to almost all tested motivational systems. For some measures, including anxiety-related behavioral parameters, there were clear gender effects. The high-anxiety phenotype of A/J mice could be shown to represent a primary and robust characteristic. Further, blood plasma and brain magnesium levels were significantly correlated with several anxiety-related behavioral parameters. These results emphasize the hypothesized, and possibly causal, association between magnesium status and emotionality. © 2010 Elsevier Inc.

Vlak M.H.M.,Rudolf Magnus Institute of Neuroscience | Vlak M.H.M.,Slotervaart Hospital | Rinkel G.J.E.,Rudolf Magnus Institute of Neuroscience | Greebe P.,Rudolf Magnus Institute of Neuroscience | And 2 more authors.
Stroke | Year: 2013

BACKGROUND AND PURPOSE-: Knowledge about risk factors contributes to understanding the pathophysiological mechanisms that cause intracranial aneurysm rupture and helps to develop possible treatment strategies. We aimed to study lifestyle and personal characteristics as risk factors for the rupture of intracranial aneurysms. METHODS-: We performed a case-control study with 250 patients with an aneurysmal subarachnoid hemorrhage and 206 patients with an unruptured intracranial aneurysm. All patients with an aneurysmal subarachnoid hemorrhage and patients with a unruptured intracranial aneurysm were asked to fill in a structured questionnaire about their lifestyle and medical history. For patients with an unruptured intracranial aneurysm, we also collected data on the indication for imaging. With logistic regression analysis, we identified independent risk factors for aneurysmal rupture. RESULTS-: Reasons for imaging in patients with an unruptured intracranial aneurysm were atherosclerotic disease (23%), positive family history (18%), headache (8%), preventive screening (3%), and other (46%). Factors that increased risk for aneurysmal rupture were smoking (odds ratio, 1.9; 95% confidence interval, 1.2-3.0) and migraine (2.4; 1.1-5.1); hypercholesterolemia decreased this risk (0.4; 0.2-1.0), whereas a history of hypertension did not independently influence the risk. CONCLUSIONS-: Smoking, migraine and, inversely, hypercholesterolemia are independent risk factors for aneurysmal rupture. Data from the questionnaire are insufficient to conclude whether hypercholesterolemia or its treatment with statins exerts a risk-reducing effect. The pathophysiological mechanisms through which smoking and migraine increase the risk of aneurysmal rupture should be investigated in further studies. Although a history of hypertension does not increase risk of rupture, a sudden rise in blood pressure might still trigger aneurysmal rupture. © 2013 American Heart Association, Inc.

Baarendse P.J.J.,Rudolf Magnus Institute of Neuroscience | Counotte D.S.,University of Maryland Baltimore County | O'Donnell P.,University of Maryland Baltimore County | Vanderschuren L.J.M.J.,Rudolf Magnus Institute of Neuroscience | Vanderschuren L.J.M.J.,University Utrecht
Neuropsychopharmacology | Year: 2013

Social experiences during youth are thought to be critical for proper social and cognitive development. Conversely, social insults during development can cause long-lasting behavioral impairments and increase the vulnerability for psychopathology later in life. To investigate the importance of social experience during the juvenile and early adolescent stage for the development of cognitive control capacities, rats were socially isolated from postnatal day 21 to 42 followed by re-socialization until they reached adulthood. Subsequently, two behavioral dimensions of impulsivity (impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task) and decision making (in the rat gambling task) were assessed. In a separate group of animals, long-lasting cellular and synaptic changes in adult medial prefrontal cortex (PFC) pyramidal neurons were determined following social isolation. Juvenile and early adolescent social isolation resulted in impairments in impulsive action and decision making under novel or challenging circumstances. Moreover, socially isolated rats had a reduced response to enhancement of dopaminergic neurotransmission (using amphetamine or GBR12909) in the 5-CSRTT under challenging conditions. Impulsive choice was not affected by social isolation. These behavioral deficits were accompanied by a loss of sensitivity to dopamine of pyramidal neurons in the medial PFC. Our data show long-lasting deleterious effects of early social isolation on cognitive control and its neural substrates. Alterations in prefrontal cognitive control mechanisms may contribute to the enhanced risk for psychiatric disorders induced by aberrations in the early social environment. © 2013 American College of Neuropsychopharmacology. All rights reserved.

Kanhai D.A.,University Utrecht | Kranendonk M.E.,University Utrecht | Uiterwaal C.S.P.M.,Julius Center for Health science and Primary Care | Van der Graaf Y.,Julius Center for Health science and Primary Care | And 3 more authors.
Obesity Reviews | Year: 2013

Summary: The plasma concentration of adiponectin, an adipokine that has anti-inflammatory, anti-atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a target for therapy. In order to review and meta-analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using 'adiponectin' and 'cardiovascular disease' or 'stroke' and their synonyms, excluding patients with clinically manifest vascular disease. Random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose-response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta-analyses. An increase of 1 standard deviation in log-transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86-1.09). A 10μg mL-1 increase in adiponectin conferred a RR of 0.91 (95% CI 0.80-1.03) for CHD and a RR 1.01 (95% CI 0.97-1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke. © 2013 International Association for the Study of Obesity.

De Rooij N.K.,Rudolf Magnus Institute of Neuroscience | Greving J.P.,University Utrecht | Rinkel G.J.E.,Rudolf Magnus Institute of Neuroscience | Frijns C.J.M.,Rudolf Magnus Institute of Neuroscience
Stroke | Year: 2013

BACKGROUND AND PURPOSE-: To develop and validate a risk chart for prediction of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on admission characteristics. METHODS-: For derivation of the risk chart, we studied data from 371 prospectively collected consecutive subarachnoid hemorrhage patients with a confirmed aneurysm admitted between 1999 and 2007. For its validation we similarly studied 255 patients admitted between 2007 and 2009. The predictive value of admission characteristics was tested in logistic regression models with delayed cerebral ischemia-related infarction as primary outcome. Procedure-related infarctions were not included. Performance of the models was tested by discrimination and calibration. On the basis of these models, a risk chart was developed for application in clinical practice. RESULTS-: The strongest predictors were clinical condition on admission, amount of blood on computed tomography (both cisternal and intraventricular) and age. A model that combined these 4 predictors had an area under the receiver operating characteristic curve of 0.63 (95% confidence interval, 0.57-0.69). This model improved little by including current smoking and hyperglycemia on admission (area under the receiver operating characteristic curve, 0.65; 95% confidence interval, 0.59-0.71). The risk chart predicted risks of delayed cerebral ischemia-related infarction varying from 12% to 61%. Both low risk (<20% risk) and high risk (>40% risk) were predicted in ≈20% of the patients. Validation confirmed that the discriminative ability was adequate (area under the receiver operating characteristic curve, 0.69; 95% confidence interval, 0.61-0.77). CONCLUSIONS-: Absolute risks of delayed cerebral ischemia-related infarction can be reliably estimated by a simple risk chart that includes clinical condition on admission, amount of blood on computed tomography (both cisternal and intraventricular), and age. © 2013 American Heart Association, Inc.

Kahn R.S.,Rudolf Magnus Institute of Neuroscience | Keefe R.S.E.,Duke University
JAMA Psychiatry | Year: 2013

Schizophrenia is currently classified as a psychotic disorder. This article posits that this emphasis on psychosis is a conceptual fallacy that has greatly contributed to the lack of progress in our understanding of this illness and hence has hampered the development of adequate treatments. Not only have cognitive and intellectual underperformance consistently been shown to be risk factors for schizophrenia, several studies have found that a decline in cognitive functioning precedes the onset of psychosis by almost a decade. Although the question of whether cognitive function continues to decline after psychosis onset is still debated, it is clear that cognitive function in schizophrenia is related to outcome and little influenced by antipsychotic treatment. Thus, our focus on defining (and preventing) the disorder on the basis of psychotic symptoms may be too narrow. Not only should cognition be recognized as the core component of the disorder, our diagnostic efforts should emphasize the changes in cognitive function that occur earlier in development. Putting the focus back on cognition may facilitate finding treatments for the illness before psychosis ever emerges.

Creemers H.,Academic Medical Center Amsterdam | Veldink J.H.,Rudolf Magnus Institute of Neuroscience | Grupstra H.,Academic Medical Center Amsterdam | Nollet F.,Academic Medical Center Amsterdam | And 2 more authors.
Neurology | Year: 2014

Objectives: To study the effect of case management on quality of life, caregiver strain, and perceived quality of care (QOC) in patients with amyotrophic lateral sclerosis (ALS) and their caregivers. Methods: We conducted a multicenter cluster randomized controlled trial with the multidisciplinary ALS care team as the unit of randomization. During 12 months, patients with ALS and their caregivers received case management plus usual care or usual care alone. Outcome measures were the 40-item ALS Assessment Questionnaire (ALSAQ-40), Emotional Functioning domain (EF); the Caregiver Strain Index (CSI); and the QOC score. These measures were assessed at baseline and at 4, 8, and 12 months. Results: Case management resulted in no changes in ALSAQ-40 EF, CSI, or QOC from baseline to 12 months. ALSAQ-40 EF scores in both groups were similar at baseline and did not change over time (p = 0.331). CSI scores in both groups increased significantly (p < 0.0001). Patients with ALS from both groups rated their perceived QOC at baseline with a median score of 8, which did not change significantly during follow-up. Conclusion: Within the context of multidisciplinary ALS care teams, case management appears to confer no benefit for patients with ALS or their caregivers. Classification of evidence: This study provides Class III evidence that case management in addition to multidisciplinary ALS care does not significantly improve health-related quality of life of patients with ALS. © 2013 American Academy of Neurology.

Van Liempt S.,Research Center Military Mental Health Care | Van Liempt S.,Rudolf Magnus Institute of Neuroscience | Van Zuiden M.,Research Center Military Mental Health Care | Westenberg H.,Rudolf Magnus Institute of Neuroscience | And 2 more authors.
Depression and Anxiety | Year: 2013

Background A significant proportion of soldiers return from deployment with symptoms of fatigue, sleep difficulties, and posttraumatic complaints. Disrupted sleep has been proposed as a contributing factor for the development of posttraumatic stress disorder (PTSD). This study investigates the impact of impaired sleep and nightmares before deployment on the development of PTSD symptoms. Method We collected reports on insomnia symptoms and nightmares in 453 Dutch service members prior to military deployment to Afghanistan. PTSD symptoms were assessed at 6 months postdeployment. The predictive value of insomnia symptoms and nightmares on the development of PTSD symptoms was assessed with a logistic regression analyses, in which was controlled for predeployment mood and anxiety symptoms. Results Self-reported predeployment nightmares predicted PTSD symptoms at 6 months (odds ratio 2.992, 95% confidence interval (CI) 1.096-8.551, P <.05), while predeployment insomnia complaints did not (odds ratio 0.976, 95% CI 0.862-1.155, P >.05). Conclusion In conclusion, this prospective longitudinal cohort study indicates that the existence of predeployment nightmares is associated with an increased risk for the development of PTSD symptoms. Nightmares may be related to hampered fear extinction memory consolidation, which has been associated with REM sleep. © 2013 Wiley Periodicals, Inc.

Loading Rudolf Magnus Institute of Neuroscience collaborators
Loading Rudolf Magnus Institute of Neuroscience collaborators