Levinson S.C.,Max Planck Institute for Psycholinguistics |
Levinson S.C.,Donders Institute for Brain
Trends in Cognitive Sciences | Year: 2016
Most language usage is interactive, involving rapid turn-taking. The turn-taking system has a number of striking properties: turns are short and responses are remarkably rapid, but turns are of varying length and often of very complex construction such that the underlying cognitive processing is highly compressed. Although neglected in cognitive science, the system has deep implications for language processing and acquisition that are only now becoming clear. Appearing earlier in ontogeny than linguistic competence, it is also found across all the major primate clades. This suggests a possible phylogenetic continuity, which may provide key insights into language evolution. © 2015 Elsevier Ltd.
Jensen O.,Donders Institute for Brain |
Mazaheri A.,Donders Institute for Brain
Frontiers in Human Neuroscience | Year: 2010
In order to understand the working brain as a network, it is essential to identify the mechanisms by which information is gated between regions. We here propose that information is gated by inhibiting task-irrelevant regions, thus routing information to task-relevant regions. The functional inhibition is reflected in oscillatory activity in the alpha band (8-13 Hz). From a physiological perspective the alpha activity provides pulsed inhibition reducing the processing capabilities of a given area. Active processing in the engaged areas is reflected by neuronal synchronization in the gamma band (30-100 Hz) accompanied by an alpha band decrease. According to this framework the brain could be studied as a network by investigating crossfrequency interactions between gamma and alpha activity. Specifically the framework predicts that optimal task performance will correlate with alpha activity in task-irrelevant areas. In this review we will discuss the empirical support for this framework. Given that alpha activity is by far the strongest signal recorded by EEG and MEG, we propose that a major part of the electrophysiological activity detected from the working brain reflects gating by inhibition. © 2010 Jensen and Mazaheri.
Homberg J.R.,Donders Institute for Brain
Brain Research | Year: 2012
There is high consensus that stress-related disorders like depression are shaped by nature × nurture interactions. However, the complexity appears larger than envisaged and nature × nurture research is progressing too slowly. An important reason is that mainstream research is focussing on the idea that a combination of genotypic stress-sensitivity and stress exposure inevitably leads to maladaptive stress-coping responses, and thereby stress-related disorders. However, stress-coping responses can also be adaptive and adhere to the expected norm. Here I elaborate the 'environment' mismatch hypothesis proposed by Mathias Schmidt (Psychoneuroendocrinology, 36, 330-338, 2011) to the stress-coping (mis)match (SCM) hypothesis postulating that stress-coping responses-as programmed by nature × age-dependent nurture interactions-are adaptive when they match current stress conditions, but maladaptive when they mismatch current stress conditions. For instance, acquisition of an active stress-coping response during nurture may lead to the programmed release of active coping responses in current life. This is adaptive when current stress is escapable, but maladaptive when current stress is inescapable, leading to agitation. A model par example for nature × nurture interactions is the serotonin transporter promoter polymorphism, which will be discussed in the framework of the SCM hypothesis. The potential role of the prefrontal-amygdala circuit and the therapeutic implications of the SCM hypothesis will also be discussed. © 2011 Elsevier B.V.
van der Voet M.,Donders Institute for Brain
Molecular Psychiatry | Year: 2015
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant dopamine signaling is thought to be a major theme in ADHD, but how this relates to the vast majority of ADHD candidate genes is illusive. Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. It represents an equally useful outcome measure for testing chemical compounds to define novel treatment options.Molecular Psychiatry advance online publication, 12 May 2015; doi:10.1038/mp.2015.55. © 2015 Macmillan Publishers Limited
Navratilova Z.,Donders Institute for Brain |
Battaglia F.P.,Donders Institute for Brain
Neuron | Year: 2015
In this issue of Neuron, Mankin etal. (2015) show that CA2, an oft-neglected hippocampal subregion, has place representations that change from one episode to the next, even as the spatial environment does not. This finding may help explain how time is encoded in episodic memories. © 2015 Elsevier Inc.
Witteveen J.S.,Donders Institute for Brain
Nature Genetics | Year: 2016
Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Muller C.P.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Homberg J.R.,Donders Institute for Brain
Behavioural Brain Research | Year: 2015
The use of psychoactive drugs is a wide spread behaviour in human societies. The systematic use of a drug requires the establishment of different drug use-associated behaviours which need to be learned and controlled. However, controlled drug use may develop into compulsive drug use and addiction, a major psychiatric disorder with severe consequences for the individual and society. Here we review the role of the serotonergic (5-HT) system in the establishment of drug use-associated behaviours on the one hand and the transition and maintenance of addiction on the other hand for the drugs: cocaine, amphetamine, methamphetamine, MDMA (ecstasy), morphine/heroin, cannabis, alcohol, and nicotine. Results show a crucial, but distinct involvement of the 5-HT system in both processes with considerable overlap between psychostimulant and opioidergic drugs and alcohol. A new functional model suggests specific adaptations in the 5-HT system, which coincide with the establishment of controlled drug use-associated behaviours. These serotonergic adaptations render the nervous system susceptible to the transition to compulsive drug use behaviours and often overlap with genetic risk factors for addiction. Altogether we suggest a new trajectory by which serotonergic neuroadaptations induced by first drug exposure pave the way for the establishment of addiction. © 2014 Elsevier B.V.
Claassen J.A.H.R.,Donders Institute for Brain
European Journal of Pharmacology | Year: 2015
The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care. © 2015 Elsevier B.V. All rights reserved.
Janssen C.I.F.,Donders Institute for Brain |
Kiliaan A.J.,Donders Institute for Brain
Progress in Lipid Research | Year: 2014
Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life.© 2013 Elsevier Ltd. All rights reserved.
Guclu U.,Donders Institute for Brain |
van Gerven M.A.J.,Donders Institute for Brain
Journal of Neuroscience | Year: 2015
Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream. © 2015, the authors.