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Schippers M.B.,University of Groningen | Roebroeck A.,Maastricht University | Renken R.,University of Groningen | Nanetti L.,University of Groningen | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Both the putative mirror neuron system (pMNS) and the ventral medial prefrontal cortex (vmPFC) are deemed important for social interaction: the pMNS because it supposedly "resonates" with the actions of others, the vmPFC because it is involved in mentalizing. Strictly speaking, the resonance property of the pMNS has never been investigated. Classical functional MRI experiments have only investigated whether pMNS regions augment their activity when an action is seen or executed. Resonance, however, entails more than only "going on and off together". Activity in the pMNS of an observer should continuously follow the more subtle changes over time in activity of the pMNS of the actor. Here we directly explore whether such resonance indeed occurs during continuous streams of actions. We let participants play the game of charades while we measured brain activity of both gesturer and guesser. We then applied a method to localize directed influences between the brains of the participants: between-brain Granger-causalitymapping. Results show that a guesser's brain activity in regions involved in mentalizing and mirroring echoes the temporal structure of a gesturer's brain activity. This provides evidence for resonance theories and indicates a fine-grained temporal interplay between regions involved in motor planning and regions involved in thinking about themental states of others. Furthermore, this method enables experiments to be more ecologically valid by providing the opportunity to leave social interaction unconstrained. This, in turn, would allow us to tap into the neural substrates of social deficits such as autism spectrum disorder.


Janssen S.F.,Royal Netherlands Academy of Arts and science KNAW | Gorgels T.G.M.F.,Royal Netherlands Academy of Arts and science KNAW | Ramdas W.D.,Erasmus Medical Center | Klaver C.C.W.,Erasmus Medical Center | And 3 more authors.
Progress in Retinal and Eye Research | Year: 2013

Primary open angle glaucoma (POAG) is a complex progressive optic nerve neuropathy triggered by both environmental and genetic risk factors. Several ocular tissues, including the ciliary body, trabecular meshwork and optic nerve head, and perhaps even brain tissues, are involved in a chain of pathological events leading to POAG.Genetic risk evidence for POAG came from family linkage-studies implicating a small number of disease genes (MYOC, OPTN, WDR36). Recent Genome Wide Association Studies (GWAS) identified a large number of new POAG loci and disease genes, such as CAV1, CDKN2B and GAS7. In the current study, we reviewed over 120 family and GWA studies. We selected in total 65 (candidate) POAG disease genes and proceeded to assess their function, mRNA expression in POAG relevant eye tissues and possible changes in disease state. We found that the proteins corresponding to these 65 (candidate) POAG disease genes take part in as few as four common functional molecular networks. Functions attributed to these 4 networks were developmental (dys)function, lipid metabolism, and inflammatory processes. For the 65 POAG disease genes, we reviewed the available (transgenic) mouse models of POAG, which may be useful for future functional studies. Finally, we showed that the 65 (candidate) POAG genes substantially increased the specificity and sensitivity of a discriminative POAG risk test. This suggests that personal risk assessment and personalized medicine for POAG are on the horizon. Taken together, the data presented are essential to comprehend the role of genetic variation in POAG, and may provide leads to understand the pathophysiology of POAG as well as other neurodegenerative disorders, such as Alzheimer's disease. © 2013 Elsevier Ltd.


Kokal I.,University of Groningen | Keysers C.,University of Groningen | Keysers C.,Royal Netherlands Academy of Arts and science KNAW
PLoS ONE | Year: 2010

Studies investigating joint actions have suggested a central role for the putative mirror neuron system (pMNS) because of the close link between perception and action provided by these brain regions [1,2,3]. In contrast, our previous functional magnetic resonance imaging (fMRI) experiment demonstrated that the BOLD response of the pMNS does not suggest that it directly integrates observed and executed actions during joint actions [4]. To test whether the pMNS might contribute indirectly to the integration process by sending information to brain areas responsible for this integration (integration network), here we used Granger causality mapping (GCM) [5]. We explored the directional information flow between the anterior sites of the pMNS and previously identified integrative brain regions. We found that the left BA44 sent more information than it received to both the integration network (left thalamus, right middle occipital gyrus and cerebellum) and more posterior nodes of the pMNS (BA2). Thus, during joint actions, two anatomically separate networks therefore seem effectively connected and the information flow is predominantly from anterior to posterior areas of the brain. These findings suggest that the pMNS is involved indirectly in joint actions by transforming observed and executed actions into a common code and is part of a generative model that could predict the future somatosensory and visual consequences of observed and executed actions in order to overcome otherwise inevitable neural delays. © 2010 Kokal, Keysers.


Thioux M.,Royal Netherlands Academy of Arts and science KNAW | Keysers C.,University of Groningen
NeuroImage | Year: 2015

We used fMRI to study the effect of hiding the target of a grasping action on the cerebral activity of an observer whose task was to anticipate the size of the object being grasped. Activity in the putative mirror neuron system (pMNS) was higher when the target was concealed from the view of the observer and anticipating the size of the object being grasped requested paying attention to the hand kinematics. In contrast, activity in ventral visual areas outside the pMNS increased when the target was fully visible, and the performance improved in this condition. A repetition suppression analysis demonstrated that in full view, the size of the object being grasped by the actor was encoded in the ventral visual stream. Dynamic causal modeling showed that monitoring a grasping action increased the coupling between the parietal and ventral premotor nodes of the pMNS. The modulation of the functional connectivity between these nodes was correlated with the subject's capability to detect the size of hidden objects. In full view, synaptic activity increased within the ventral visual stream, and the connectivity with the pMNS was diminished. The re-enactment of observed actions in the pMNS is crucial when interpreting others' actions requires paying attention to the body kinematics. However, when the context permits, visual-spatial information processing may complement pMNS computations for improved action anticipation accuracy. © 2014 Elsevier Inc.


Alves C.H.,Royal Netherlands Academy of Arts and science KNAW | Pellissier L.P.,Royal Netherlands Academy of Arts and science KNAW | Wijnholds J.,Royal Netherlands Academy of Arts and science KNAW
Progress in Retinal and Eye Research | Year: 2014

The early developing retinal neuroepithelium is composed of multipotent retinal progenitor cells that differentiate in a time specific manner, giving rise to six major types of neuronal and one type of glial cells. These cells migrate and organize in three distinct nuclear layers divided by two plexiform layers. Apical and adherens junction complexes have a crucial role in this process by the establishment of polarity and adhesion. Changes in these complexes disturb the spatiotemporal aspects of retinogenesis, leading to retinal degeneration resulting in mild or severe impairment of retinal function and vision.In this review, we summarize the mouse models for the different members of the apical and adherens junction protein complexes and describe the main features of their retinal phenotypes. The knowledge acquired from the different mutant animals for these proteins corroborate their importance in retina development and maintenance of normal retinal structure and function. More recently, several studies have tried to unravel the connection between the apical proteins, important cellular signaling pathways and their relation in retina development. Still, the mechanisms by which these proteins function remain largely unknown. Here, we hypothesize how the mammalian apical CRB1 complex might control retinogenesis and prevents onset of Leber congenital amaurosis or retinitis pigmentosa. © 2014 Elsevier Ltd.


Ausloos M.,Royal Netherlands Academy of Arts and science KNAW | Ausloos M.,Group of Researchers for Applications of Physics in economics and Sociology GRAPES
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2014

The Lavalette function is generalized to a two-exponent function in order to represent data looking like a sigmoid on semilogarithmic plots. A Mandelbrot trick is suggested for further investigations, if more fit parameters are needed. The analyzed data is that of the number of adherents to the main religions in the 20th century. © 2014 American Physical Society.


de Gruijl J.R.,Royal Netherlands Academy of Arts and science KNAW | Bazzigaluppi P.,Erasmus University Rotterdam | de Jeu M.T.G.,Erasmus University Rotterdam | de Zeeuw C.I.,Royal Netherlands Academy of Arts and science KNAW | de Zeeuw C.I.,Erasmus University Rotterdam
PLoS Computational Biology | Year: 2012

The inferior olivary nucleus provides one of the two main inputs to the cerebellum: the so-called climbing fibers. Activation of climbing fibers is generally believed to be related to timing of motor commands and/or motor learning. Climbing fiber spikes lead to large all-or-none action potentials in cerebellar Purkinje cells, overriding any other ongoing activity and silencing these cells for a brief period of time afterwards. Empirical evidence shows that the climbing fiber can transmit a short burst of spikes as a result of an olivary cell somatic spike, potentially increasing the information being transferred to the cerebellum per climbing fiber activation. Previously reported results from in vitro studies suggested that the information encoded in the climbing fiber burst is related to the occurrence of the spike relative to the ongoing sub-threshold membrane potential oscillation of the olivary cell, i.e. that the phase of the oscillation is reflected in the size of the climbing fiber burst. We used a detailed three-compartmental model of an inferior olivary cell to further investigate the possible factors determining the size of the climbing fiber burst. Our findings suggest that the phase-dependency of the burst size is present but limited and that charge flow between soma and dendrite is a major determinant of the climbing fiber burst. From our findings it follows that phenomena such as cell ensemble synchrony can have a big effect on the climbing fiber burst size through dendrodendritic gap-junctional coupling between olivary cells. © 2012 de Gruijl et al.


van Kerkoerle T.,Royal Netherlands Academy of Arts and science KNAW | Self M.W.,Royal Netherlands Academy of Arts and science KNAW | Dagnino B.,Royal Netherlands Academy of Arts and science KNAW | Gariel-Mathis M.-A.,Royal Netherlands Academy of Arts and science KNAW | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.


van Zutphen L.,Maastricht University | Siep N.,Maastricht University | Jacob G.A.,Albert Ludwigs University of Freiburg | Goebel R.,Maastricht University | And 3 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2015

Emotional sensitivity, emotion regulation and impulsivity are fundamental topics in research of borderline personality disorder (BPD). Studies using fMRI examining the neural correlates concerning these topics is growing and has just begun understanding the underlying neural correlates in BPD. However, there are strong similarities but also important differences in results of different studies. It is therefore important to know in more detail what these differences are and how we should interpret these. In present review a critical light is shed on the fMRI studies examining emotional sensitivity, emotion regulation and impulsivity in BPD patients. First an outline of the methodology and the results of the studies will be given. Thereafter important issues that remained unanswered and topics to improve future research are discussed. Future research should take into account the limited power of previous studies and focus more on BPD specificity with regard to time course responses, different regulation strategies, manipulation of self-regulation, medication use, a wider range of stimuli, gender effects and the inclusion of a clinical control group. © 2015 Elsevier Ltd.


Lefebvre C.,University of Montréal | Dell'acqua R.,University of Padua | Roelfsema P.R.,Royal Netherlands Academy of Arts and science KNAW | JolicAeur P.,University of Montréal
Psychophysiology | Year: 2011

Mental curve tracing is the process by which a contour is covertly followed between two landmarks. Completion time of this task increases as the distance between the landmarks does, even though the Euclidian distance is constant. This has been taken as evidence that attention does not cover a contour instantly, but rather moves from one point to another until the whole contour has been covered. This article provides an electrophysiological measurement of the time course of this spread of attention in humans using a sustained contralateral posterior negative (SPCN) event-related potential component. This component being elicited only when stimuli are presented laterally, the position of lateralization was varied to modulate the onset of this SPCN. Curves that became lateralized further from the central starting point yielded a later SPCN onset than curves that lateralized nearer. This provides converging evidence that attention moves along the curve. © 2011 Society for Psychophysiological Research.

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