Brundel M.,Brain Center Rudolf Magnus |
Kwa V.I.H.,Onze Lieve Vrouwe Gasthuis |
Bouvy W.H.,Brain Center Rudolf Magnus |
Algra A.,Brain Center Rudolf Magnus |
And 3 more authors.
Cerebrovascular Diseases | Year: 2014
Background: Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. Methods: Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n = 397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n = 280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n = 48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. Results: The mean age was 65 ± 12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70 ± 9 vs. 64 ± 12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p < 0.05). The mean TICS score was 35.3 ± 5.9 for patients with microbleeds (n = 29) and 34.6 ± 5.2 for patients without microbleeds (n = 251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0 ± 10.8 for patients with microbleeds (n = 9) and 63.1 ± 12.9 for patients without microbleeds (n = 39); the adjusted mean difference was 2.43 (-7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63-2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient β: -0.12 (-0.23 to 0.00); p = 0.04] and with lower IQCODE score [0.51 (0.19-0.83); p = 0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12-0.65; p = 0.01). Conclusions: In this sample of patients with a recent TIA or minor ischemic stroke, microbleeds were not associated with cognitive performance 4 years later. Apparently, this association is different from other markers of small vessel disease. © 2014 S. Karger AG, Basel.
Bruining H.,University Utrecht |
Bruining H.,Brain Center Rudolf Magnus |
Eijkemans M.J.,Brain Center Rudolf Magnus |
Eijkemans M.J.,University Utrecht |
And 4 more authors.
Molecular Autism | Year: 2014
Background: Autism spectrum disorder (ASD) is well recognized to be genetically heterogeneous. It is assumed that the genetic risk factors give rise to a broad spectrum of indistinguishable behavioral presentations. Methods. We tested this assumption by analyzing the Autism Diagnostic Interview-Revised (ADI-R) symptom profiles in samples comprising six genetic disorders that carry an increased risk for ASD (22q11.2 deletion, Down's syndrome, Prader-Willi, supernumerary marker chromosome 15, tuberous sclerosis complex and Klinefelter syndrome; total n = 322 cases, groups ranging in sample sizes from 21 to 90 cases). We mined the data to test the existence and specificity of ADI-R profiles using a multiclass extension of support vector machine (SVM) learning. We subsequently applied the SVM genetic disorder algorithm on idiopathic ASD profiles from the Autism Genetics Resource Exchange (AGRE). Results: Genetic disorders were associated with behavioral specificity, indicated by the accuracy and certainty of SVM predictions; one-by-one genetic disorder stratifications were highly accurate leading to 63% accuracy of correct genotype prediction when all six genetic disorder groups were analyzed simultaneously. Application of the SVM algorithm to AGRE cases indicated that the algorithm could detect similarity of genetic behavioral signatures in idiopathic ASD subjects. Also, affected sib pairs in the AGRE were behaviorally more similar when they had been allocated to the same genetic disorder group. Conclusions: Our findings provide evidence for genotype-phenotype correlations in relation to autistic symptomatology. SVM algorithms may be used to stratify idiopathic cases of ASD according to behavioral signature patterns associated with genetic disorders. Together, the results suggest a new approach for disentangling the heterogeneity of ASD. © 2014 Bruining et al.; licensee BioMed Central Ltd.
News Article | November 17, 2016
The University Medical Center Utrecht (UMC) has announced the success of a brain implant in a Dutch patient suffering from ALS disease that enables her to operate a speech computer with her mind. Fifty-nine year-old mother-of-three Hanneke de Bruijne was diagnosed with ALS (Lou Gehrig's disease) in 2008 and can no longer move or speak, yet her mind is fully functional. The electrode implanted in her brain picks up brain activity and enables her to wirelessly control a speech computer to communicate with family and caregivers. What's more, she uses the technology not in a laboratory but at home and it is mobile enough to travel, promising a new life for those otherwise locked in non-functioning bodies. Computers are going to become much better at repairing human cognitive and sensory-motor functions in the not-too-distant future, and the UMC achievement signifies another milestone in humanity's relationship with the computer. This announcement also marks a milestone in assisting and augmenting (not just repairing) human cognitive and sensory-motor functions, and gives us a peak at a future world where communication by thought alone might be possible. "This is a major breakthrough in achieving autonomous communication among severely paralyzed patients whose paralysis is caused by either ALS, a cerebral hemorrhage or trauma," said Nick Ramsey, Professor of Cognitive Neuroscience at UMC Utrecht. "In effect, this patient has had a kind of remote control placed in her head, which enables her to operate a speech computer without the use of her muscles." Hanneke de Bruijne underwent surgery last year to implant the electrodes on her brain, with the wires passing through tiny holes in her skull and a small transmitter was then placed in her body below her collarbone. This transmitter receives the signals from the electrodes via subcutaneous wires, amplifies them and transmits them wirelessly to the computer. The speech computer is operated by Hanneke de Bruijne moving her fingers "in her mind." This brain activity is detected by the electrodes, and the movement is converted into a mouse click. On a screen in front of her, Hanneke de Bruijne can construct words and sentences using a dedicated interface designed for the task, and those words are in turn vocalized by the speech computer. This is similar to using a speech computer via a push-button interface, but with a brain signal used instead to actuate the button instead of a muscle. Trials of the implant are currently underway with three patients, and the researchers hope to progress to a larger, international trial following that phase. "We hope that these results will stimulate research into more advanced implants, so that some day not only people with communication problems, but also people with paraplegia, for example, can be helped," says Ramsey. This research that enabled this breakthrough was conducted by the UMC Utrecht Brain Center Rudolf Magnus through its Utrecht NeuroProsthesis Project (UNP) and is funded by the technology foundation STW. The implant itself came from medical technology company Medtronic.
News Article | November 14, 2016
At UMC Utrecht, a brain implant has been placed in a patient enabling her to operate a speech computer with her mind. The researchers and the patient worked intensively to get the settings right. She can now communicate at home with her family and caregivers via the implant. That a patient can use this technique at home is unique in the world. This research was published in the New England Journal of Medicine. Because she suffers from ALS disease, the patient is no longer able to move and speak. Doctors placed electrodes in her brain, and the electrodes pick up brain activity. This enables her to wirelessly control a speech computer that she now uses at home. "This is a major breakthrough in achieving autonomous communication among severely paralyzed patients whose paralysis is caused by either ALS, a cerebral hemorrhage or trauma," says Professor Nick Ramsey, professor of cognitive neuroscience at the University Medical Center (UMC) Utrecht. "In effect, this patient has had a kind of remote control placed in her head, which enables her to operate a speech computer without the use of her muscles." The patient operates the speech computer by moving her fingers in her mind. This changes the brain signal under the electrodes. That change is converted into a mouse click. On a screen in front of her she can see the alphabet, plus some additional functions such as deleting a letter or word and selecting words based on the letters she has already spelled. The letters on the screen light up one by one. She selects a letter by influencing the mouse click at the right moment with her brain. That way she can compose words, letter by letter, which are then spoken by the speech computer. This technique is comparable to actuating a speech computer via a push-button (with a muscle that can still function, for example, in the neck or hand). So now, if a patient lacks muscle activity, a brain signal can be used instead. The patient underwent surgery during which electrodes were placed on her brain through tiny holes in her skull. A small transmitter was then placed in her body below her collarbone. This transmitter receives the signals from the electrodes via subcutaneous wires, amplifies them and transmits them wirelessly. The mouse click is calculated from these signals, actuating the speech computer. The patient is closely supervised. Shortly after the operation, she started on a journey of discovery together with the researchers to find the right settings for the device and the perfect way to get her brain activity under control. It started with a "simple" game to practice the art of clicking. Once she mastered clicking, she focused on the speech computer. She can now use the speech computer without the help of the research team. The UMC Utrecht Brain Center has spent many years researching the possibility of controlling a computer by means of electrodes that capture brain activity. Working with a speech computer driven by brain signals measured with a bathing cap with electrodes has long been tested in various research laboratories. That a patient can use the technique at home, through invisible, implanted electrodes, is unique in the world. If the implant proves to work well in three people, the researchers hope to launch a larger, international trial. Ramsey: "We hope that these results will stimulate research into more advanced implants, so that some day not only people with communication problems, but also people with paraplegia, for example, can be helped." This research is part of the Utrecht NeuroProsthesis (UNP) project conducted by the UMC Utrecht Brain Center Rudolf Magnus, and is funded by technology foundation STW. The implant itself was provided by one of the R&D departments of medical technology company Medtronic.
Wisse L.E.M.,Brain Center Rudolf Magnus |
Wisse L.E.M.,Julius Center for Health science and Primary Care |
Biessels G.J.,Brain Center Rudolf Magnus |
Heringa S.M.,Brain Center Rudolf Magnus |
And 4 more authors.
Neurobiology of Aging | Year: 2014
We compared hippocampal subfield and entorhinal cortex (ERC) volumes between patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and controls without cognitive impairment. Additionally, we investigated the relation between age and hippocampal subfields and ERC in controls. We performed ultra-high field 0.7 mm3 7Tesla magnetic resonance imaging in 16 patients with amnestic MCI, 9 with AD, and 29 controls. ERC, subiculum, cornu ammonis (CA)1, CA2, CA3, and dentate gyrus (DG)&CA4 were traced on T2-weighted images. Analyses of covariance, adjusted for age, sex, and intracranial volume showed that compared with controls and patients with MCI, patients with AD had significantly smaller ERC, subiculum, CA1, CA3, and DG&CA4 volumes. Trend analyses revealed similar associations between ERC and hippocampal subfields and diagnostic group. Older age was significantly associated with smaller CA1 and DG&CA4 volumes. In conclusion, almost all hippocampal subfields and ERC show volume reductions in patients with AD compared with controls and patients with MCI. Future, larger studies should determine which subfields are affected earliest in the disease process and what mechanisms underlie the volume loss. © 2014 Elsevier Inc.
Schellekens W.,Brain Center Rudolf Magnus |
van Wezel R.J.A.,Radboud University Nijmegen |
van Wezel R.J.A.,University of Twente |
Petridou N.,Image science Institute Radiology |
And 2 more authors.
Brain Structure and Function | Year: 2016
The current study investigates if early visual cortical areas, V1, V2 and V3, use predictive coding to process motion information. Previous studies have reported biased visual motion responses at locations where novel visual information was presented (i.e., the motion trailing edge), which is plausibly linked to the predictability of visual input. Using high-field functional magnetic resonance imaging (fMRI), we measured brain activation during predictable versus unpreceded motion-induced contrast changes during several motion stimuli. We found that unpreceded moving dots appearing at the trailing edge gave rise to enhanced BOLD responses, whereas predictable moving dots at the leading edge resulted in suppressed BOLD responses. Furthermore, we excluded biases in directional sensitivity, shifts in cortical stimulus representation, visuo-spatial attention and classical receptive field effects as viable alternative explanations. The results clearly indicate the presence of predictive coding mechanisms in early visual cortex for visual motion processing, underlying the construction of stable percepts out of highly dynamic visual input. © 2014, Springer-Verlag Berlin Heidelberg.
Goedee S.H.,UMC Utrecht |
Goedee S.H.,Brain Center Rudolf Magnus |
Brekelmans G.J.F.,St Elisabeth Hospital |
van den Berg L.H.,UMC Utrecht |
And 2 more authors.
Clinical Neurophysiology | Year: 2015
Objective: The extent of sonomorphologic differences of peripheral nerves between CMT and HNPP is unknown. Methods: We recruited 9 patients with CMT-1A and 9 with HNPP. Patients underwent a standardized sonographic protocol, which evaluated nerve size and vascularization. We quantitatively assessed fascicle size and echogenicity. Results: All 18 patients demonstrated nerve enlargement, but no increased vascularization. HNPP demonstrated larger nerves at sites of entrapment (median nerve at the carpal tunnel p= 0.049, ulnar nerve at the sulcus p<. 0.001), greater swelling ratios of median (p<. 0.001), ulnar (p. = 0.017) and fibular nerve (p= 0.005) than CMT-1A. CMT-1A revealed larger nerves proximal to sites of entrapment (median and fibular nerve, brachial plexus p<. 0.001). Nerve fascicles where larger (p<. 0.001) and more hypo-echogenic in CMT-1A. Nerve, fascicle size nor echogenicity correlated with age, gender or MRC sum-score. Conclusions: Ultrasonography of nerves reveals specific phenotypes differentiating CMT-1A from HNPP. In CMT-1A enlargement of nerves and fascicles is multifocal among multiple nerves, whereas in HNPP nerve enlargement is restricted to sites of entrapment. Significance: Our findings of specific sonomorphological phenotypes, differentiating CMT-1A from HNPP, may help to improve our pathophysiological insights in CMT and HNPP. © 2014 International Federation of Clinical Neurophysiology.
Collin G.,University Utrecht |
Collin G.,Brain Center Rudolf Magnus |
Kahn R.S.,University Utrecht |
Kahn R.S.,Brain Center Rudolf Magnus |
And 6 more authors.
Schizophrenia Bulletin | Year: 2014
Schizophrenia has been conceptualized as a disorder of brain connectivity. Recent studies suggest that brain connectivity may be disproportionally impaired among the so-called rich club. This small core of densely interconnected hub regions has been hypothesized to form an important infrastructure for global brain communication and integration of information across different systems of the brain. Given the heritable nature of the illness, we hypothesized that connectivity disturbances, including abnormal rich club connectivity, may be related to familial vulnerability for schizophrenia. To test this hypothesis, both schizophrenia patients and unaffected siblings of patients were investigated. Rich club organization was examined in networks derived from diffusion-weighted imaging in 40 schizophrenia patients, 54 unaffected siblings of patients, and 51 healthy control subjects. Connectivity between rich club hubs was differentially reduced across groups (P =. 014), such that it was highest in controls, intermediate in siblings (7.9% reduced relative to controls), and lowest in patients (19.6% reduced compared to controls). Furthermore, in patients, lower levels of rich club connectivity were found to be related to longer duration of illness and worse overall functioning. Together, these findings suggest that impaired rich club connectivity is related to familial, possibly reflecting genetic, vulnerability for schizophrenia. Our findings support a central role for abnormal rich club organization in the etiology of schizophrenia. © 2013 The Author. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
Jongbloets B.C.,Brain Center Rudolf Magnus |
Jeroen Pasterkamp R.,Brain Center Rudolf Magnus
Development (Cambridge) | Year: 2014
Semaphorins are secreted and membrane-associated proteins that regulate many different developmental processes, including neural circuit assembly, bone formation and angiogenesis. Trans and cis interactions between semaphorins and their multimeric receptors trigger intracellular signal transduction networks that regulate cytoskeletal dynamics and influence cell shape, differentiation, motility and survival. Here and in the accompanying poster we provide an overview of the molecular biology of semaphorin signalling within the context of specific cell and developmental processes, highlighting the mechanisms that act to fine-tune, diversify and spatiotemporally control the effects of semaphorins. © 2014. Published by The Company of Biologists Ltd.
Kronenburg A.,Brain Center Rudolf Magnus |
Braun K.P.J.,Brain Center Rudolf Magnus |
Van Der Zwan A.,Brain Center Rudolf Magnus |
Klijn C.J.M.,Brain Center Rudolf Magnus
Current Neurology and Neuroscience Reports | Year: 2014
Moyamoya disease is a progressive intracranial arteriopathy characterized by bilateral stenosis of the distal portion of the internal carotid artery and the proximal anterior and middle cerebral arteries, resulting in transient ischemic attacks or strokes. The pathogenesis of moyamoya disease remains unresolved, but recent advances have suggested exciting new insights into a genetic contribution as well as into other pathophysiological mechanisms. Treatment that may halt progression of the disease or even reverse the intracranial arteriopathy is yet to be found. There are strong indications that neurosurgical intervention, through direct, indirect, or combined revascularization surgery, can reduce the risk of ischemic stroke and possibly also cognitive dysfunction by improving cerebral perfusion, although randomized clinical trials have not been performed. Many questions regarding the indication for and timing of surgery remain unanswered. In this review, we discuss recent developments in the pathogenesis and treatment of moyamoya disease. © 2013 Springer Science+Business Media New York.