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  • 51.
    Fransén, Erik
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Coexistence of synchronized oscillatory and desynchronized rate activity in cortical networks2003In: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. apr-52, p. 763-769Article in journal (Refereed)
    Abstract [en]

    The basis of MRI and PET experiments is the finding that neuronal cell firing levels are modulated in a task dependent manner. Results from EEG and MEG experiments on the other hand point to the importance of synchrony, e.g. the peak frequency may depend on the difficulty of the task. In most models only one of these activity modes of firing is desirable or possible to produce. In this work we show how a cortical microcircuit can produce either synchronized or desynchronized firing, and how this solves problems of present day rate and synchronization models.

  • 52.
    Fransén, Erik
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Functional role of Entorhinal cortex in working memory and information processing of the medial temporal lobe2004In: 2004 IEEE INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-4, PROCEEDINGS, 2004, p. 621-624Conference paper (Refereed)
    Abstract [en]

    Our learning and memory system has the challenge to work in a world where items to learn are dispersed in space and time. From the information extracted by the perceptual systems, the learning system must select and combine information. Both these operations may require a temporary storage where significance and correlations may be assessed. This work builds on the common hypothesis that hippocampus and subicular, entorhinal and parahippocampal/postrhinal areas are essential for these functions. We bring up two examples of models, one modeling in vivo and in vitro data from entorhinal cortex layer II of delay match-to-sample working memory experiments, and one modeling slice data from layer V showing cellular "integrator-like" intrinsically generated stable graded levels of spiking activity. In both cases we discuss how cationic currents might be involved and relate their kinetics and pharmacology to behavioral and cellular experimental results.

  • 53.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
    Functional role of entorhinal cortex in working memory processing2005In: Neural Networks, ISSN 0893-6080, E-ISSN 1879-2782, Vol. 18, no 9, p. 1141-1149Article in journal (Refereed)
    Abstract [en]

    Our learning and memory system has the challenge to work in a world where items to learn are dispersed in space and time. From the information extracted by the perceptual systems, the learning system must select and combine information. Both these operations may require a temporary storage where significance and correlations could be assessed. This work builds on the common hypothesis that hippocampus and subicular, entorhinal and parahippocampal/postrhinal areas are essential for the above-mentioned functions. We bring up two examples of models: the first one is modeling of in vivo and in vitro data from entorhinal cortex layer 11 of delayed match-to-sample working memory experiments, the second one studying mechanisms in theta rhythmicity in EC. In both cases, we discuss how cationic currents might be involved and relate their kinetics and pharmacology to behavioral and cellular experimental results.

  • 54.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Neural response profile design: Reducing epileptogenic activity by modifying neuron responses to synchronized input using novel potassium channels obtained by parameter search optimization2007In: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 70, no 10-12, p. 1630-1634Article in journal (Refereed)
    Abstract [en]

    Neurons obtain their dynamical electrical characteristics by a set of ion channels. These properties may not only affect the function of the neuron and the local network it forms part of, but it may also eventually affect behavior. We were interested to study whether epileptogenic activity could be reduced by adding an ion channel. In this work, we used computational search techniques to optimize ion channel properties for the goal of modifying neural response characteristics. Our results show that this type of parameter search is possible and reasonably efficient. Successful searches were generated using the direct method PRAXIS, and by systematic searches in low-dimensional sub-spaces. We also report on unsuccessful searches using a simplex-type method, a gradient-based method, and attempts to reduce goal function evaluation time. Importantly, using this search strategy, our study has shown that it is possible to change a neuron's characteristics selectively with regard to response to degree of synchronicity in synaptic input.

  • 55.
    Fransén, Erik
    et al.
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Alonso, A. A.
    Dickson, C. T.
    Magistretti, J.
    Hasselmo, M. E.
    Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons2004In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 14, no 3, p. 368-384Article in journal (Refereed)
    Abstract [en]

    A multi compartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (I-NaP) and the hyperpolarization activated inward current (I-h) in the generation of subthreshold membrane potential oscillations. The potential role of I-h in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of I-h and the slow calcium-activated potassium current I-K(AHP) in action potential clustering was also studied. Representations of I-h and I-NaP were developed with parameters based on voltage-clamp data from whole-cell patch and single channel recordings of stellate cells (Dickson et A, J Neurophysiol 83:2562-2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491-509, 1999; Magistretti et al., J Physiol 521:629-636, 1999a; J Neurosci 19:7334-7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of I-h with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of I-h does not follow the fast component down to very short time constants. The model also predicts that the fast component of I-h is responsible for the involvement in the generation of subthreshold oscillations, and the slow component dominates in the generation of spike clusters.

  • 56.
    Fransén, Erik
    et al.
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Alonso, A. A.
    Hasselmo, M. E.
    Entorhinal neuronal activity during delayed matching tasks may depend upon muscarinic-induced non-specific cation current I(CANM)2001In: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 38, p. 601-606Article in journal (Refereed)
    Abstract [en]

    Biophysical compartmental models of stellate, pyramidal-like and interneurons in layer II of the rat entorhinal cortex were used to explore cellular and synaptic components involved in neuronal responses to stimuli in a delayed match to sample (DMS) task. Simulations demonstrate that the muscarinic receptor-induced non-specific cation current, I(CANM), could contribute to these phenomena. Facilitation of I(CANM) by calcium influx during spikes induced by the sample stimulus can cause enhanced responses for matches as well as delay activity. In a network, lateral inhibition can produce match suppression, and in conjunction with stimulus selective/non-selective cells produce non-match enhancement and suppression.

  • 57.
    Fransén, Erik
    et al.
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Alonso, A. A.
    Hasselmo, M. E.
    Simulations of the role of the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM in entorhinal neuronal activity during delayed matching tasks2002In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 22, no 3, p. 1081-1097Article in journal (Refereed)
    Abstract [en]

    Entorhinal lesions impair performance in delayed matching tasks, and blockade of muscarinic cholinergic receptors also impairs performance in these tasks. Physiological data demonstrate that muscarinic cholinergic receptor stimulation activates intrinsic cellular currents in entorhinal neurons that could underlie the role of entorhinal cortex in performance of these tasks. Here we use a network biophysical simulation of the entorhinal cortex to demonstrate the potential role of this cellular mechanism in the behavioral tasks. Simulations demonstrate how the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM could provide a cellular mechanism for features of the neuronal activity observed during performance of delayed matching tasks. In particular, I-NCM could underlie (1) the maintenance of sustained spiking activity during the delay period, (2) the enhancement of spiking activity during the matching period relative to the sample period, and (3) the resistance of sustained activity to distractors. Simulation of a larger entorhinal network with connectivity chosen randomly within constraints on number, distribution, and weight demonstrates appearance of other phenomena observed in unit recordings from awake animals, including match suppression, non-match enhancement, and non-match suppression.

  • 58.
    Fransén, Erik
    et al.
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Lansner, Anders
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    A model of cortical associative memory based on a horizontal network of connected columns1998In: Network, ISSN 0954-898X, E-ISSN 1361-6536, Vol. 9, no 2, p. 235-264Article in journal (Refereed)
    Abstract [en]

    An attractor network model of cortical associative memory functions has been constructed and simulated. By replacing the single cell as the functional unit by multiple cells in cortical columns connected by long-range fibers, the model is improved in terms of correspondence with cortical connectivity. The connectivity is improved, since the original dense and symmetric connectivity of a standard recurrent network becomes sparse and asymmetric at the cell-to-cell level. Our simulations show that this kind of network, with model neurons of the Hodgkin-Huxley type arranged in columns, can operate as an associative memory in much the same way as previous models having simpler connectivity. The network shows attractor-like behaviour and performs the standard assembly operations despite differences in the dynamics introduced by the more detailed cell model and network structure. Furthermore, the model has become sufficiently detailed to allow evaluation against electrophysiological and anatomical observations. For instance, cell activities comply with experimental findings and reaction times are within biological and psychological ranges. By introducing a scaling model we demonstrate that a network approaching experimentally reported neuron numbers and synaptic distributions also could work like the model studied here.

  • 59.
    Fransén, Erik
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Petersson, Marcus E.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Tigerholm, Jenny
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Andersson, Sten
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Obreja, O
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Lampert, A
    Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
    Carr, R
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Schmelz, M
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Differences in action potential propagation in mechanosensitive and insensitive C-nociceptors - a modeling approach2012Conference paper (Refereed)
    Abstract [en]

    C-fibers, unmyelinated afferent axons, convey information from the periphery of the nervous system to the spinal cord. They transmit signals originating from noxious stimulation evoking the sensations of itch and pain in the central nervous system. Different classes of C-fibers are characterized by functional, morphological and biochemical characteristics. In pain studies, a classification into mechano-insensitive (CMi) and mechano responsive fibers (CM) has proven useful as changes in proportions and response characteristics of these fibers have been observed in neuropathy patients (Weidner et al. 1999, 2000; Orstavik 2003, 2010). In this study, using computational modeling of a C-fiber, we have studied the possible contribution of different ion channel subtypes (Na-TTXs, Nav1.8, Nav1.9, Kdr, KA, KM, K(Na), h) as well as the Na/K-ATPase pump to conductive properties of C-fibers. In particular we investigated mechanisms that could generate the fiber-specific differences between CM and CMi fibers with regard to activity dependent slowing (ADS) and recovery cycles (RC). In our study we represent the axon by three cylindrical sections, one representing the peripheral thin end (branch, 2.5 cm), one the central part (parent, 10 cm) and a conical section between these (0.5 cm). In total 730 compartments are used. Temperature is set to 32 degrees C in branch and 37 degrees in parent sections. We represent variable ion concentrations of Na and K intra axonally, periaxonally and extracellularly, from which reversal potentials are calculated. We use ion channel models based on Hodgkin Huxley formalism. An ion pump (Na/K-ATPase) is included. We find that TTX-sensitive Na and Nav1.8 have the strongest influence on action potential conduction velocity as is expected since these are the major components of the rising phase of the action potential. Preliminary observations indicate that a small subset of Na and K currents play a key role in determining differences in activity dependent velocity changes (ADS) in the two fiber classes. We plan to also study contributions from morphological characteristics (superficial branch lengths) to activity dependent differences between the fiber classes (Schmidt et al. 2002). We further intend to investigate candidate ion channels which could play a role in changing the functional characteristics of a CMi fiber to that of a CM fiber. Our studies may provide insights into ionic changes underlying changes in the excitability of C-fibers associated with pain.

  • 60.
    Fransén, Erik
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Tahvildari, B.
    Egorov, A. V.
    Hasselmo, M. E.
    Alonso, A. A.
    Mechanism of graded persistent cellular activity of entorhinal cortex layer V neurons2006In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 49, no 5, p. 735-746Article in journal (Refereed)
    Abstract [en]

    Working memory is an emergent property of neuronal networks, but its cellular basis remains elusive. Recent data show that principal neurons of the entorhinal cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model provides stable plateau firing generated by a nonspecific calcium-sensitive cationic (CAN) current. Sustained firing is insensitive to small variations in Ca2+ concentration in a neutral zone. However, both high and low Ca2+ levels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high levels of calcium, while decreases in rate occur in the presence of low levels of calcium. The model is consistent with detailed experimental observations and provides a mechanism for maintenance of memory-related activity in individual neurons.

  • 61.
    Fransén, Erik
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Tigerholm, Jenny
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Role of A-type potassium currents in excitability, network synchronicity, and epilepsy2010In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 20, no 7, p. 877-887Article in journal (Refereed)
    Abstract [en]

    A range of ionic currents have been suggested to be involved in distinct aspects of epileptogenesis. Based on pharmacological and genetic studies, potassium currents have been implicated, in particular the transient A-type potassium current (K-A). Epileptogenic activity comprises a rich repertoire of characteristics, one of which is synchronized activity of principal cells as revealed by occurrences of for instance fast ripples. Synchronized activity of this kind is particularly efficient in driving target cells into spiking. In the recipient cell, this synchronized input generates large brief compound excitatory postsynaptic potentials (EPSPs). The fast activation and inactivation of K-A lead us to hypothesize a potential role in suppression of such EPSPs. In this work, using computational modeling, we have studied the activation of K-A by synaptic inputs of different levels of synchronicity. We find that K-A participates particularly in suppressing inputs of high synchronicity. We also show that the selective suppression stems from the current's ability to become activated by potentials with high slopes. We further show that K-A suppresses input mimicking the activity of a fast ripple. Finally, we show that the degree of selectivity of K-A can be modified by changes to its kinetic parameters, changes of the type that are produced by the modulatory action of KChIPs and DPPs. We suggest that the wealth of modulators affecting K-A might be explained by a need to control cellular excitability in general and suppression of responses to synchronicity in particular. We also suggest that compounds changing K-A-kinetics may be used to pharmacologically improve epileptic status.

  • 62.
    Fransén, Erik
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Tigerholm, Jenny
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Petersson, Marcus E.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Carr, R
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, German.
    Obreja, O
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Lampert, A
    Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
    Schmelz, M
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Computational modeling of activity dependent velocity changes in peripheral C-fibers2011Conference paper (Refereed)
    Abstract [en]

    Initiation and propagation of action potentials along unmyelinated C-fibers are the first steps of the pain pathway. Propagation velocity and its fiber class-specific activity-dependent slowing (ADS) is intimately linked to fibre excitability. In chronic pain patients, ADS alterations have been suggested to reflect increased excitability, possibly underlying clinical pain. Due to their small diameter, peripheral axons of nociceptors in patients are not accessible for intraaxonal recordings of their ion channel properties. We have therefore constructed a model of a C-fibre to study the relationship between ion channel composition and velocity changes as well as excitability. Ion channels are modeled from data of DRG somata using a Hodgkin-Huxley formalism (Na currents: TTX-sensitive, Nav1.8, Nav1.9, K currents: Kdr, A-type, Kv7.3, non-specific cationic: HCN). Moreover, ion pumps (Na/K-ATPase) and concentrations of intra and extraaxonal sodium and potassium are also included. The geometry and temperature of the fibre represents a section of the superficial branch and the deeper parent and is represented by a multicompartmental structure where each compartment contains passive as well as ion channel and pump elements. Using parameter estimation techniques, we optimized ion channel and pump expression pattern such that basic electrophysiological characteristics of the action potential and its velocity matched the experimental data. Moreover, we have also replicated activity dependent slowing. In ongoing work, we extend optimization to also include recovery cycles. The model will be used to study hypothesis of the relationship between individual ion channel subtypes and axonal excitability related to pain, generating independent information on impact of selective neuronal targets.

  • 63. Froriep, Ulrich P
    et al.
    Kumar, Arvind
    University of Freiburg, Germany.
    Cosandier-Rimélé, Delphine
    Häussler, Ute
    Kilias, Antje
    Haas, Carola A
    Egert, Ulrich
    Altered theta coupling between medial entorhinal cortex and dentate gyrus in temporal lobe epilepsy2012In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 53, no 11, p. 1937-1947Article in journal (Refereed)
    Abstract [en]

    Purpose: Temporal lobe epilepsy is often accompanied by neuron loss and rewiring in the hippocampus. We hypothesized that the interaction of subnetworks of the entorhinalhippocampal loop between epileptic events should show significant signatures of these pathologic changes.

    Methods: We combined simultaneous recording of local field potentials in entorhinal cortex (EC) and dentate gyrus (DG) in freely behaving kainate-injected mice with histologic analyses and computational modeling.

    Key Findings: In healthy mice, theta band activity was synchronized between EC and DG. In contrast, in epileptic mice, theta activity in the EC was delayed with respect to the DG. A computational neural mass model suggests that hippocampal cell loss imbalances the coupling of subnetworks, introducing the shift.

    Significance: We show that pathologic dynamics in epilepsy encompass ongoing activity in the entorhinal-hippocampal loop beyond acute epileptiform activity. This predominantly affects theta band activity, which links this shift in entorhinal-hippocampal interaction to behavioral aspects in epilepsy.

  • 64. Giocomo, Lisa M.
    et al.
    Zilli, Eric A.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Hasselmo, Michael E.
    Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing2007In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 315, no 5819, p. 1719-1722Article in journal (Refereed)
    Abstract [en]

    Grid cells in layer II of rat entorhinal cortex fire to spatial locations in a repeating hexagonal grid, with smaller spacing between grid fields for neurons in more dorsal anatomical locations. Data from in vitro whole-cell patch recordings showed differences in frequency of subthreshold membrane potential oscillations in entorhinal neurons that correspond to different positions along the dorsal-to-ventral axis, supporting a model of physiological mechanisms for grid cell responses.

  • 65. Gliga, Anda R.
    et al.
    Edoff, Karin
    Caputo, Fanny
    Kallman, Thomas
    Blom, Hans
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karlsson, Hanna L.
    Ghibelli, Lina
    Traversa, Enrico
    Ceccatelli, Sandra
    Fadeel, Bengt
    Cerium oxide nanoparticles inhibit differentiation of neural stem cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9284Article in journal (Refereed)
    Abstract [en]

    Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific beta 3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.

  • 66. Gospic, Katarina
    et al.
    Sundberg, Marcus
    KTH, School of Architecture and the Built Environment (ABE), Transport Science, Transport and Location Analysis. KTH, School of Architecture and the Built Environment (ABE), Centres, Centre for Transport Studies, CTS.
    Maeder, Johanna
    Fransson, Peter
    Petrovic, Predrag
    Isacsson, Gunnar
    Karlström, Anders
    KTH, School of Architecture and the Built Environment (ABE), Transport Science, Transport and Location Analysis. KTH, School of Architecture and the Built Environment (ABE), Centres, Centre for Transport Studies, CTS.
    Ingvar, Martin
    Altruism costs-the cheap signal from amygdala2014In: Social Cognitive & Affective Neuroscience, ISSN 1749-5016, E-ISSN 1749-5024, Vol. 9, no 9, p. 1325-1332Article in journal (Refereed)
    Abstract [en]

    When people state their willingness to pay for something, the amount usually differs from the behavior in a real purchase situation. The discrepancy between a hypothetical answer and the real act is called hypothetical bias. We investigated neural processes of hypothetical bias regarding monetary donations to public goods using fMRI with the hypothesis that amygdala codes for real costs. Real decisions activated amygdala more than hypothetical decisions. This was observed for both accepted and rejected proposals. The more the subjects accepted real donation proposals the greater was the activity in rostral anterior cingulate cortex-a region known to control amygdala but also neural processing of the cost-benefit difference. The presentation of a charitable donation goal evoked an insula activity that predicted the later decision to donate. In conclusion, we have identified the neural mechanisms underlying real donation behavior, compatible with theories on hypothetical bias. Our findings imply that the emotional system has an important role in real decision making as it signals what kind of immediate cost and reward an outcome is associated with.

  • 67. Grah, Gunnar
    et al.
    Kumar, Arvind
    Wettstreit der Metaphern2014In: Geist und Gehirn, ISSN 1618-8519, no 7, p. 60-65Article, review/survey (Other (popular science, discussion, etc.))
  • 68. Grah, Gunnar
    et al.
    Kumar, Arvind
    Zittern in zahlen2013In: Geist und Gehirn, ISSN 1618-8519, no 5, p. 68-73Article, review/survey (Other (popular science, discussion, etc.))
  • 69.
    Grangeray-Vilmint, Anais
    et al.
    Univ Strasbourg, CNRS, Inst Neurosci Cellulaires & Integrat, F-67084 Strasbourg, France..
    Valera, Antoine M.
    Univ Strasbourg, CNRS, Inst Neurosci Cellulaires & Integrat, F-67084 Strasbourg, France.;UCL, Dept Neurosci Physiol & Pharmacol, London, England..
    Kumar, Arvind
    KTH, School of Electrical Engineering and Computer Science (EECS).
    Isope, Philippe
    Univ Strasbourg, CNRS, Inst Neurosci Cellulaires & Integrat, F-67084 Strasbourg, France..
    Short-Term Plasticity Combines with Excitation-Inhibition Balance to Expand Cerebellar Purkinje Cell Dynamic Range2018In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 38, no 22, p. 5153-5167Article in journal (Refereed)
    Abstract [en]

    The balance between excitation (E) and inhibition (I) in neuronal networks controls the firing rate of principal cells through simple network organization, such as feedforward inhibitory circuits. Here, we demonstrate in male mice, that at the granule cell (GrC)molecular layer interneuron (MLI)-Purkinje cell (PC) pathway of the cerebellar cortex, E/I balance is dynamically controlled by short-term dynamics during bursts of stimuli, shaping cerebellar output. Using a combination of electrophysiological recordings, optogenetic stimulation, and modeling, we describe the wide range of bidirectional changes in PC discharge triggered by GrC bursts, from robust excitation to complete inhibition. At high frequency (200 Hz), increasing the number of pulses in a burst (from 3 to 7) can switch a net inhibition of PC to a net excitation. Measurements of EPSCs and IPSCs during bursts and modeling showed that this feature can be explained by the interplay between short-term dynamics of the GrC-MLI-PC pathway and E/I balance impinging on PC. Our findings demonstrate that PC firing rate is highly sensitive to the duration of GrC bursts, which may define a temporal-to-rate code transformation in the cerebellar cortex.

  • 70. Groselj, L. Dolenc
    et al.
    Morrison, S. A.
    Rojc, B.
    Mirnik, D.
    Korsic, S.
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Mekjavic, I. B.
    Hypoxic bedrest and sleep architecture: effect of initial hypoxic exposure and total stimulus duration2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, p. 236-236Article in journal (Other academic)
  • 71. Groselj, L. Dolenc
    et al.
    Morrison, S.
    Univ Med Ctr, Inst Clin Neurophysiol, Ljubljana, Slovenia..
    Mirnik, D.
    Univ Med Ctr, Inst Clin Neurophysiol, Ljubljana, Slovenia..
    Korsic, S.
    Univ Med Ctr, Inst Clin Neurophysiol, Ljubljana, Slovenia..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. Royal Inst Technol, Sch Technol & Hlth, Dept Environm Physiol, Stockholm, Sweden..
    Mekjavic, I.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot, Ljubljana, Slovenia..
    Prolonged bed rest and hypoxic exposure affect breathing stability and sleep macrostructure2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, p. 744-744Article in journal (Other academic)
  • 72. Groselj, L. Dolenc
    et al.
    Rojc, B.
    Jeran, J.
    Pangerc, A.
    Morrison, S. A.
    Eiken, Ola
    KTH, School of Technology and Health (STH), Environmental Physiology.
    Mekjavic, I. B.
    Effect of bed rest and hypoxia on sleep macrostructure and respiration during sleep2012In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 21, p. 63-63Article in journal (Other academic)
  • 73. Gunnarson, E.
    et al.
    Axehult, G.
    Baturina, G.
    Zelenin, S.
    Zelenina, Marina
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Aperia, A.
    Lead induces increased water permeability in astrocytes expressing aquaporin 42005In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 136, no 1, p. 105-114Article in journal (Refereed)
    Abstract [en]

    The water channel aquaporin 4 (AQP4) is abundantly expressed in astrocytes. There is now compelling evidence that AQP4 may contribute to an unfavorable course in brain edema. Acute lead intoxication is a condition that causes brain damage preceded by brain edema. Here we report that lead increases AQP4 water permeability (P-f) in astrocytes. A rat astrocyte cell line that does not express aquaporin 4 was transiently transfected with aquaporin 4 tagged with green fluorescent protein (GFP). Using confocal laser scanning microscopy we measured water permeability in these cells and in AQP4-negative cells located on the same plate. AQP4-expressing astrocytes had a three-fold higher water permeability than astrocytes not expressing AQP4. Lead exposure induced a significant, 40%, increase in water permeability in astrocytes expressing AQP4, but had no effect on Pf in astrocytes not expressing AQP4. The increase in water permeability persisted after lead washout, while treatment with a lead chelator, meso-2,3-dimercaptosuccinic acid, abolished the lead-induced increase in Pf. The effect of lead was attenuated in the presence of a calcium (Ca2+)/ calmodulin-dependent protein kinase 11 (CaMKII) inhibitor, but not in the presence of a protein kinase C inhibitor. In cells expressing AQP4 where the consensus site for CaMKII phosphorylation was mutated, lead failed to increase water permeability. Lead exposure also increased Pf in rat astroglial cells in primary culture, which express endogenous AQP4. Lead had no effect on Pf in astrocytes transfected with aquaporin 3. In situ hybridization studies on rat brain after oral lead intake for three days showed no change in distribution of AQP4 mRNA. It is suggested that lead-triggered stimulation of water transport in AQP4-expressing astrocytes may contribute to the pathology of acute lead intoxication.

  • 74. Gunnarson, E.
    et al.
    Zelenina, Marina
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Song, Yutong
    Illarionova, N.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson, Ulf
    Zelenin, S.
    Aperia, Anita
    Effect of the brain protecting agent erythropoietin on astrocyte function2009Conference paper (Refereed)
  • 75. Gunnarson, Eli
    et al.
    Song, Yutong
    Kowalewski, Jacob M
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brines, Michael
    Cerami, Anthony
    Andersson, Ulf
    Zelenina, Marina
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Aperia, Anita
    Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection.2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 1091-6490, Vol. 106, no 5, p. 1602-7Article in journal (Refereed)
    Abstract [en]

    Disturbed brain water homeostasis with swelling of astroglial cells is a common complication in stroke, trauma, and meningitis and is considered to be a major cause of permanent brain damage. Astroglial cells possess the water channel aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate, acting on group I metabotropic glutamate receptors (mGluRs), increases the permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will increase astrocyte water uptake. Here we report that erythropoietin (EPO), which in recent years has emerged as a potent neuro-protective agent, antagonizes the effect of a group I mGluR agonist on astrocyte water permeability. Activation of group I mGluRs triggers fast and highly regular intracellular calcium oscillations and we show that EPO interferes with this signaling event by altering the frequency of the oscillations. These effects of EPO are immediate, in contrast to the neuroprotective effects of EPO that are known to depend upon gene activation. Our findings indicate that EPO may directly reduce the risk of astrocyte swelling in stroke and other brain insults. In support of this conclusion we found that EPO reduced the neurological symptoms in a mouse model of primary brain edema known to depend upon AQP4 water transport.

  • 76. Gunnarson, Eli
    et al.
    Zelenina, Marina
    Axehult, Gustav
    Song, Yutong
    Bondar, Alexander
    Krieger, Patrik
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Zelenin, Sergey
    Aperia, Anita
    Identification of a molecular target for glutamate regulation of astrocyte water permeability2008In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 56, no 6, p. 587-596Article in journal (Refereed)
    Abstract [en]

    Astrocytes play a key role for maintenance of brain water homeostasis, but little is known about mechanisms of short-term regulation of astrocyte water permeability. Here, we report that glutamate increases astrocyte water permeability and that the molecular target for this effect is the aquaporin-4 (AQP4) serine 111 residue, which is in a strategic position for control of the water channel gating. The glutamate effect involves activation of group I metabotropic glutamate receptors (mGluR), intracellular calcium release, and activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and nitric oxide synthase (NOS). The physiological impact of our results is underlined by the finding that mGluR activation increases the rate of hypoosmotic tissue swelling in acute rat hippocampal slices. Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage. Thus, we have identified AQP4 as the molecular target for drugs that may attenuate the development of brain edema.

  • 77. Gunnarson, Eli
    et al.
    Zelenina, Marina
    Karolinska Institutet.
    Song, Yutong
    Kowalewski, Jacob M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brines, Michael
    Cerami, Antony
    Andersson, Ulf
    Aperia, Anita
    Kvinnor och barns hälsa, Karolinska Institutet.
    Erythropoietin modulation of astrocyte water permeability: a potential component of neuroprotection2008In: Neuroscience 2008, 2008Conference paper (Refereed)
  • 78.
    Gutierrez, Elena
    et al.
    Chalmers University of Technology, Crash Safety Division.
    Huang, Yinglai
    Department of Anatomy and Cell Biology, Göteborg University.
    Haglid, Kenneth
    Department of Anatomy and Cell Biology, Göteborg University.
    Bao, Feng
    Department of Anatomy and Cell Biology, Göteborg University.
    Hansson, Hans-Arne
    Department of Anatomy and Cell Biology, Göteborg University.
    Hamberger, Anders
    Department of Anatomy and Cell Biology, Göteborg University.
    Viano, David
    Crash Safety Division, Chalmers University of Technology.
    A New Model for Diffuse Brain Injury by Rotational Acceleration: I. Model, Gross Appearance, and Astrocytosis2001In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 18, no 3, p. 247-257Article in journal (Refereed)
  • 79. Hahn, Gerald
    et al.
    Bujan, Alejandro F
    Frégnac, Yves
    Aertsen, Ad
    Kumar, Arvind
    Univ Freiburg, Germany.
    Communication through resonance in spiking neuronal networks2014In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 10, no 8, article id e1003811Article in journal (Refereed)
    Abstract [en]

    The cortex processes stimuli through a distributed network of specialized brain areas. This processing requires mechanisms that can route neuronal activity across weakly connected cortical regions. Routing models proposed thus far are either limited to propagation of spiking activity across strongly connected networks or require distinct mechanisms that create local oscillations and establish their coherence between distant cortical areas. Here, we propose a novel mechanism which explains how synchronous spiking activity propagates across weakly connected brain areas supported by oscillations. In our model, oscillatory activity unleashes network resonance that amplifies feeble synchronous signals and promotes their propagation along weak connections ("communication through resonance''). The emergence of coherent oscillations is a natural consequence of synchronous activity propagation and therefore the assumption of different mechanisms that create oscillations and provide coherence is not necessary. Moreover, the phase-locking of oscillations is a side effect of communication rather than its requirement. Finally, we show how the state of ongoing activity could affect the communication through resonance and propose that modulations of the ongoing activity state could influence information processing in distributed cortical networks.

  • 80.
    Hahn, Gerald
    et al.
    Univ Pompeu Fabra, Ctr Brain & Cognit, Computat Neurosci Grp, Dept Informat & Commun Technol, Barcelona, Spain..
    Ponce-Alvarez, Adrian
    Univ Pompeu Fabra, Ctr Brain & Cognit, Computat Neurosci Grp, Dept Informat & Commun Technol, Barcelona, Spain..
    Deco, Gustavo
    Univ Pompeu Fabra, Ctr Brain & Cognit, Computat Neurosci Grp, Dept Informat & Commun Technol, Barcelona, Spain.;Univ Pompeu Fabra, Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain..
    Aertsen, Ad
    Univ Freiburg, Fac Biol, Freiburg, Germany.;Univ Freiburg, Bernstein Ctr Freiburg, Freiburg, Germany..
    Kumar, Arvind
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST).
    Portraits of communication in neuronal networks2019In: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 20, no 2, p. 117-127Article, review/survey (Refereed)
    Abstract [en]

    The brain is organized as a network of highly specialized networks of spiking neurons. To exploit such a modular architecture for computation, the brain has to be able to regulate the flow of spiking activity between these specialized networks. In this Opinion article, we review various prominent mechanisms that may underlie communication between neuronal networks. We show that communication between neuronal networks can be understood as trajectories in a two-dimensional state space, spanned by the properties of the input. Thus, we propose a common framework to understand neuronal communication mediated by seemingly different mechanisms. We also suggest that the nesting of slow (for example, alpha-band and theta-band) oscillations and fast (gamma-band) oscillations can serve as an important control mechanism that allows or prevents spiking signals to be routed between specific networks. We argue that slow oscillations can modulate the time required to establish network resonance or entrainment and, thereby, regulate communication between neuronal networks.

  • 81.
    Harischandra, Nalin
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Knuesel, Jeremei
    EPFL.
    Kozlov, Alexander
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Bicanski, Andrej
    EPFL.
    Cabelguen, Jean-Marie
    Neurocentre Magendie, Bordeaux University, Bordeaux Cedex, France.
    Ijspeert, Auke
    EPFL.
    Ekeberg, Örjan
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Sensory feedback plays a significant role in generating walking gait and in gait transition in salamanders: a simulation study2011In: Frontiers in Neurorobotics, ISSN 1662-5218, Vol. 5, p. 3:1-3:13Article in journal (Refereed)
    Abstract [en]

    Here, we investigate the role of sensory feedback in gait generation and transition by using a three-dimensional, neuro-musculo-mechanical model of a salamander with realistic physical parameters. Activation of limb and axial muscles were driven by neural output patterns obtained from a central pattern generator (CPG) which is composed of simulated spiking neurons with adaptation. The CPG consists of a body-CPG and four limb-CPGs that are interconnected via synapses both ipsilaterally and contralaterally. We use the model both with and without sensory modulation and four different combinations of ipsilateral and contralateral coupling between the limb-CPGs. We found that the proprioceptive sensory inputs are essential in obtaining a coordinated lateral sequence walking gait (walking). The sensory feedback includes the signals coming from the stretch receptor like intraspinal neurons located in the girdle regions and the limb stretch receptors residing in the hip and scapula regions of the salamander. On the other hand, walking trot gait (trotting) is more under central (CPG) influence compared to that of the peripheral or sensory feedback. We found that the gait transition from walking to trotting can be induced by increased activity of the descending drive coming from the mesencephalic locomotor region and is helped by the sensory inputs at the hip and scapula regions detecting the late stance phase. More neurophysiological experiments are required to identify the precise type of mechanoreceptors in the salamander and the neural mechanisms mediating the sensory modulation.

  • 82. Hasselmo, M. E.
    et al.
    Fransén, Erik
    KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
    Dickson, C.
    Alonso, A. A.
    Computational modeling of entorhinal cortex2000In: PARAHIPPOCAMPAL REGION: IMPLICATIONS FOR NEUROLOGICAL AND PSYCHIATRIC DISEASES / [ed] Scharfman, HE; Witter, MP; Schwarcz, R, NEW YORK: New York Academy of Sciences, 2000, Vol. 911, p. 418-446Conference paper (Refereed)
    Abstract [en]

    Computational modeling provides a means for linking the physiological and anatomical characteristics of entorhinal cortex at a cellular level to the functional role of this region in behavior. We have developed detailed simulations of entorhinal cortical neurons and networks, with an emphasis on the role of acetylcholine in entorhinal cortical function. Computational modeling suggests that when acetylcholine levels are high, this sets appropriate dynamics for the storage of stimuli during performance of delayed matching tasks. In particular, acetylcholine activates a calcium-sensitive nonspecific cation current which provides an intrinsic cellular mechanism which could maintain neuronal activity across a delay period. Simulations demonstrate how this phenomena could underlie entorhinal cortex delay activity as described in previous unit recordings. Acetylcholine also induces theta rhythm oscillations which may be appropriate for timing of afferent input to be encoded in hippocampus and for extraction of individual stored sequences from multiple stored sequences. Lower levels of acetylcholine may allow sharp wave dynamics which can reactivate associations encoded in hippocampus and drive the formation of additional traces in hippocampus and entorhinal cortex during consolidation.

  • 83. Hasselmo, Michael E.
    et al.
    Brandon, Mark P.
    Yoshida, Motoharu
    Giocomo, Lisa M.
    Heys, James G.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Newman, Ehren L.
    Zilli, Eric A.
    A phase code for memory could arise from circuit mechanisms in entorhinal cortex2009In: Neural Networks, ISSN 0893-6080, E-ISSN 1879-2782, Vol. 22, no 8, p. 1129-1138Article in journal (Refereed)
    Abstract [en]

    Neurophysiological data reveals intrinsic cellular properties that suggest how entorhinal cortical neurons could code memory by the phase of their firing. Potential cellular mechanisms for this phase coding in models of entorhinal function are reviewed. This mechanism for phase coding provides a substrate for modeling the responses of entorhinal grid cells, as well as the replay of neural spiking activity during waking and sleep. Efforts to implement these abstract models in more detailed biophysical compartmental simulations raise specific issues that could be addressed in larger scale population models incorporating mechanisms of inhibition.

  • 84.
    Heil, Katharina F.
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). University of Edinburgh.
    A Systems Biological Approach to Parkinson's Disease2018Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Parkinson’s Disease (PD) is the second most common neurodegenerative disease in the Western world. Itshows a high degree of genetic and phenotypic complexity with many implicated factors, various diseasemanifestations but few clear causal links. Ongoing research has identified a growing number of molecularalterations linked to the disease.Dopaminergic neurons in the substantia nigra, specifically their synapses, are the key-affected region in PD.Therefore, this work focuses on understanding the disease effects on the synapse, aiming to identify potentialgenetic triggers and synaptic PD associated mechanisms. Currently, one of the main challenges in this area isdata quality and accessibility.In order to study PD, publicly available data were systematically retrieved and analysed. 418 PD associatedgenes could be identified, based on mutations and curated annotations. I curated an up-to-date and completesynaptic proteome map containing a total of 6,706 proteins. Region specific datasets describing thepresynapse, postsynapse and synaptosome were also delimited. These datasets were analysed, investigatingsimilarities and differences, including reproducibility and functional interpretations.The use of Protein-Protein-Interaction Network (PPIN) analysis was chosen to gain deeper knowledgeregarding specific effects of PD on the synapse. Thus I generated a customised, filtered, human specificProtein-Protein Interaction (PPI) dataset, containing 211,824 direct interactions, from four public databases.Proteomics data and PPI information allowed the construction of PPINs. These were analysed and a set oflow level statistics, including modularity, clustering coefficient and node degree, explaining the network’stopology from a mathematical point of view were obtained.Apart from low-level network statistics, high-level topology of the PPINs was studied. To identify functionalnetwork subgroups, different clustering algorithms were investigated. In the context of biological networks, theunderlying hypothesis is that proteins in a structural community are more likely to share common functions.Therefore I attempted to identify PD enriched communities of synaptic proteins. Once identified, they werecompared amongst each other. Three community clusters could be identified as containing largely overlappinggene sets. These contain 24 PD associated genes. Apart from the known disease associated genes in thesecommunities, a total of 322 genes was identified. Each of the three clusters is specifically enriched for specificbiological processes and cellular components, which include neurotransmitter secretion, positive regulation ofsynapse assembly, pre- and post-synaptic membrane, scaffolding proteins, neuromuscular junctiondevelopment and complement activation (classical pathway) amongst others.The presented approach combined a curated set of PD associated genes, filtered PPI information andsynaptic proteomes. Various small- and large-scale analytical approaches, including PPIN topology analysis,clustering algorithms and enrichment studies identified highly PD affected synaptic proteins and subregions.Specific disease associated functions confirmed known research insights and allowed me to propose a newlist of so far unknown potential disease associated genes. Due to the open design, this approach can be usedto answer similar research questions regarding other complex diseases amongst others.

  • 85. Hernandez, Fidel
    et al.
    Giordano, Chiara
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Camarillo, David
    CORONAL HEAD ROTATION, FALX CEREBRI DISPLACEMENT, AND CORPUS CALLOSUM STRAIN ARE RELATED AND IMPLICATED IN SPORTS-RELATED MTBI2016In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, no 13, p. A34-A35Article in journal (Other academic)
  • 86.
    Hjorth, Johannes
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
    Information processing in the Striatum: a computational study2006Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    The basal ganglia form an important structure centrally placed in the brain. They receive input from motor, associative and limbic areas, and produce output mainly to the thalamus and the brain stem. The basal ganglia have been implied in cognitive and motor functions. One way to understand the basal ganglia is to take a look at the diseases that affect them. Both Parkinson's disease and Huntington's disease with their motor problems are results of malfunctioning basal ganglia. There are also indications that these diseases affect cognitive functions. Drug addiction is another example that involves this structure, which is also important for motivation and selection of behaviour.

    In this licentiate thesis I am laying the groundwork for a detailed model of the striatum, which is the input stage of the basal ganglia. The striatum receives glutamatergic input from the cortex and thalamus, as well as dopaminergic input from substantia nigra. The majority of the neurons in the striatum are medium spiny (MS) projection neurons that project mainly to globus pallidus but also to other neurons in the striatum and to both dopamine producing and GABAergic neurons in substantia nigra. In addition to the MS neurons there are fast spiking (FS) interneurons that are in a position to regulate the firing of the MS neurons. These FS neurons are few, but connected into large networks through electrical synapses that could synchronise their effect. By forming strong inhibitory synapses on the MS neurons the FS neurons have a powerful influence on the striatal output. The inhibitory output of the basal ganglia on the thalamus is believed to keep prepared motor commands on hold, but once one of them is disinhibited, then the selected motor command is executed. This disinhibition is initiated in the striatum by the MS neurons.

    Both MS and FS neurons are active during so called up-states, which are periods of elevated cortical input to striatum. Here I have studied the FS neurons and their ability to detect such up-states. This is important because FS neurons can delay spikes in MS neurons and the time between up-state onset and the first spike in the MS neurons is correlated with the amount of calcium entering the MS neuron, which in turn might have implications for plasticity and learning of new behaviours. The effect of different combinations of electrical couplings between two FS neurons has been tested, where the location, number and strength of these gap junctions have been varied. I studied both the ability of the FS neurons to fire action potentials during the up-state, and the synchronisation between neighbouring FS neurons due to electrical coupling. I found that both proximal and distal gap junctions synchronised the firing, but the distal gap junctions did not have the same temporal precision. The ability of the FS neurons to detect an up-state was affected by whether the neighbouring FS neuron also received up-state input or not. This effect was more pronounced for distal gap junctions than proximal ones, due to a stronger shunting effect of distal gap junctions when the dendrites were synaptically activated.

    We have also performed initial stochastic simulations of the Ca2+-calmodulin-dependent protein kinase II (CaMKII). The purpose here is to build the knowledge as well as the tools necessary for biochemical simulations of intracellular processes that are important for plasticity in the MS neurons. The simulated biochemical pathways will then be integrated into an existing model of a full MS neuron. Another venue to explore is to build striatal network models consisting of MS and FS neurons and using experimental data of the striatal microcircuitry. With these different approaches we will improve our understanding of striatal information processing.

  • 87. Huttner, Hagen B.
    et al.
    Bergmann, Olaf
    Salehpour, Mehran
    Racz, Attila
    Tatarishvili, Jemal
    Lindgren, Emma
    Csonka, Tamas
    Csiba, Laszlo
    Hortobagyi, Tibor
    Mehes, Gabor
    Englund, Elisabet
    Werne Solnestam, Beata
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zdunek, Sofia
    Scharenberg, Christian
    Strom, Lena
    Stahl, Patrik
    Sigurgeirsson, Benjamin
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Dahl, Andreas
    Schwab, Stefan
    Possnert, Goran
    Bernard, Samuel
    Kokaia, Zaal
    Lindvall, Olle
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Frisen, Jonas
    The age and genomic integrity of neurons after cortical stroke in humans2014In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 17, no 6, p. 801-803Article in journal (Refereed)
    Abstract [en]

    It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived C-14 concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.

  • 88.
    Hällgren Kotaleski, Jeanette
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Blackwell, Kim T.
    Modelling the molecular mechanisms of synaptic plasticity using systems biology approaches2010In: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 11, no 4, p. 239-251Article, review/survey (Refereed)
    Abstract [en]

    Synaptic plasticity is thought to underlie learning and memory, but the complexity of the interactions between the ion channels, enzymes and genes that are involved in synaptic plasticity impedes a deep understanding of this phenomenon. Computer modelling has been used to investigate the information processing that is performed by the signalling pathways involved in synaptic plasticity in principal neurons of the hippocampus, striatum and cerebellum. In the past few years, new software developments that combine computational neuroscience techniques with systems biology techniques have allowed large-scale, kinetic models of the molecular mechanisms underlying long-term potentiation and long-term depression. We highlight important advancements produced by these quantitative modelling efforts and introduce promising approaches that use advancements in live-cell imaging.

  • 89. Jaderstad, Johan
    et al.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Herlenius, Eric
    Hypoxic preconditioning increases gap-junctional graft and host communication2010In: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 21, no 17, p. 1126-1132Article in journal (Refereed)
    Abstract [en]

    Gap-junctional intercellular communication between grafted neural stem cells (NSCs) and host cells seems to be essential for many of the functional and beneficial interactions after NSC engraftment. Gap-junctional communication is also known to increase in the central nervous system after hypoxia and ischemia. We therefore hypothesized that controlled hypoxic preconditioning of murine NSCs (C17.2) before the engraftment is a reliable method to increase connexin 43 expression and improve subsequent graft and host communication. Data indicated that 3-h exposure to hypoxia increased the number of connexin 43 aggregates in treated NSCs by 31%. This was paralleled by enhanced hemichannel function showed by faster calcein dye efflux and an augmentation of the early functional graft and host communication.

  • 90.
    Jensen, Poul Erik H.
    et al.
    Univ Copenhagen, Rigshosp, Danish Multiple Sclerosis Ctr, Dept Neurol, Sect 6311, Copenhagen, Denmark..
    Ramanujam, Ryan
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.).
    Sorensen, Per Soelberg
    Univ Copenhagen, Rigshosp, Danish Multiple Sclerosis Ctr, Dept Neurol, Sect 6311, Copenhagen, Denmark..
    Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis. Results from the ABIRISK prospective cohort study2019In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 326, p. 19-27Article in journal (Refereed)
    Abstract [en]

    Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-beta) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-beta-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-beta ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.

  • 91.
    Johansson, Christopher
    et al.
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA. KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Rehn, Martin
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
    Lansner, Anders
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
    Attractor neural networks with patchy connectivity2006In: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 69, no 7-9, p. 627-633Article in journal (Refereed)
    Abstract [en]

     The neurons in the mammalian visual cortex are arranged in columnar structures, and the synaptic contacts of the pyramidal neurons in layer II/III are clustered into patches that are sparsely distributed over the surrounding cortical surface. Here, We use an attractor neural-network model of the cortical circuitry and investigate the effects of patchy connectivity, both on the properties of the network and the attractor dynamics. An analysis of the network shows that the signal-to-noise ratio of the synaptic potential sums are improved by the patchy connectivity, which results in a higher storage capacity. This analysis is performed for both the Hopfield and Willshaw learning rules and the results are confirmed by simulation experiments.

  • 92.
    Kamali Sarvestani, Iman
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Subsystems of the basal ganglia and motor infrastructure2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The motor nervous system is one of the main systems of the body and is our principle means ofbehavior. Some of the most debilitating and wide spread disorders are motor systempathologies. In particular the basal ganglia are complex networks of the brain that control someaspects of movement in all vertebrates. Although these networks have been extensively studied,lack of proper methods to study them on a system level has hindered the process ofunderstanding what they do and how they do it. In order to facilitate this process I have usedcomputational models as an approach that can faithfully take into account many aspects of ahigh dimensional multi faceted system.In order to minimize the complexity of the system, I first took agnathan fish and amphibians asmodeling animals. These animals have rather simple neuronal networks and have been wellstudied so that developing their biologically plausible models is more feasible. I developedmodels of sensory motor transformation centers that are capable of generating basic behaviorsof approach, avoidance and escape. The networks in these models used a similar layeredstructure having a sensory map in one layer and a motor map on other layers. The visualinformation was received as place coded information, but was converted into population codedand ultimately into rate coded signals usable for muscle contractions.In parallel to developing models of visuomotor centers, I developed a novel model of the basalganglia. The model suggests that a subsystem of the basal ganglia is in charge of resolvingconflicts between motor programs suggested by different motor centers in the nervous system.This subsystem that is composed of the subthalamic nucleus and pallidum is called thearbitration system. Another subsystem of the basal ganglia called the extension system which iscomposed of the striatum and pallidum can bias decisions made by an animal towards theactions leading to lower cost and higher outcome by learning to associate proper actions todifferent states. Such states are generally complex states and the novel hypothesis I developedsuggests that the extension system is capable of learning such complex states and linking themto appropriate actions. In this framework, striatal neurons play the role of conjunction (BooleanAND) neurons while pallidal neurons can be envisioned as disjunction (Boolean OR) neurons.In the next set of experiments I tried to take the idea of basal ganglia subsystems to a new levelby dividing the rodent arbitration system into two functional subunits. A rostral group of ratpallidal neurons form dense local inhibition among themselves and even send inhibitoryprojections to the caudal segment. The caudal segment does not project back to its rostralcounterpart, but both segments send inhibitory projections to the output nuclei of the rat basalganglia i.e. the entopeduncular nucleus and substantia nigra. The rostral subsystems is capableof precisely detecting one (or several) components of a rudimentary action and suppress othercomponents. The components that are reinforced are those which lead to rewarding stateswhereas those that are suppressed are those which do not. The hypothesis explains neuronalmechanisms involved in this process and suggests that this subsystem is a means of generatingsimple but precise movements (such as using a single digit) from innate crude actions that theanimal can perform even at birth (such as general movement of the whole limb). In this way, therostral subsystem may play important role in exploration based learning.In an attempt to more precisely describe the relation between the arbitration and extensionsystems, we investigated the effect of dynamic synapses between subthalamic, pallidal andstriatal neurons and output neurons of the basal ganglia. The results imply that output neuronsare sensitive to striatal bursts and pallidal irregular firing. They also suggest that few striatalneurons are enough to fully suppress output neurons. Finally the results show that the globuspallidus exerts its effect on output neurons by direct inhibition rather than indirect influence viathe subthalamic nucleus.

  • 93.
    Kamali Sarvestani, Iman
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Ekeberg, Örjan
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Internal Connectivity of the GlobusPallidus and the Arbitration System2013Manuscript (preprint) (Other academic)
    Abstract [en]

    The rodent globus pallidus (homologue of primate external globus pallidus) has been shown to be composed of two types neuronal groups based on their location and local axon collaterals. The rostral outer layer near the striatopallidal border (GPr) has shorter but more dense local axon collaterals while the caudal inner layer (GPc) has wider and less dense axon collaterals. Moreover, the connection between the two segments is unidirectional with outer layer neurons sending inhibitory projections to the inner layer. Both segments inhibit the substantia nigra and the entopeduncular nucleus (homologue of primate internal globus pallidus). We have created a model of the basal ganglia arbitration subsystem composed of the subthalamic nucleus, the two segments of the pallidus as well as the entopeduncular nucleus and the substantia nigra in order to assess functional roles of the two pallidal segments. The simulations reveal that both segments of the pallidum are involved in winner-take-all structure of the arbitration system but the type of information competing is different in the two subsystems. In the STN-GPr network, strong lateral inhibition between pallidal neurons representing muscles leads to selection of a muscle which has been (due to noise or other reasons) randomly overactivated. In contrast, in STN-GPc network actions (each utilizing many muscles) compete. Our simulations suggest that both networks are active during selection and execution of movements. If overactivation of a muscle is accompanied with dopamine flow, the GPr-GPc connection together with local axonal network of GPc suppress other muscles and reinforce the muscle whose overactivity has caused the dopaminergic flow. Simulated lesions of these neuronal groups also show different results. Lesioning GPr results in synchronous activity in GPc and SNr but the mean firing rate of these nuclei remains untouched. Lesioning GPc on the other hand lifts the activity in the SNr drastically but does not create synchrony in any of the nuclei. The results suggest that STN-GPc and STN-GPr can be considered as two different subsystems working both in synergy and in competition.

  • 94.
    Kamali Sarvestani, Iman
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Kozlov, Alexander
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Harischandra, Nalin
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Grillner, Sten
    Karolinska Institutet.
    Ekeberg, Örjan
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    A computational model of visually guided locomotion in lamprey2013In: Biological Cybernetics, ISSN 0340-1200, E-ISSN 1432-0770, Vol. 107, no 5, p. 497-512Article in journal (Refereed)
    Abstract [en]

    This study addresses mechanisms for the generation and selection of visual behaviors in anamniotes. To demonstrate the function of these mechanisms, we have constructed an experimental platform where a simulated animal swims around in a virtual environment containing visually detectable objects. The simulated animal moves as a result of simulated mechanical forces between the water and its body. The undulations of the body are generated by contraction of simulated muscles attached to realistic body components. Muscles are driven by simulated motoneurons within networks of central pattern generators. Reticulospinal neurons, which drive the spinal pattern generators, are in turn driven directly and indirectly by visuomotor centers in the brainstem. The neural networks representing visuomotor centers receive sensory input from a simplified retina. The model also includes major components of the basal ganglia, as these are hypothesized to be key components in behavior selection. We have hypothesized that sensorimotor transformation in tectum and pretectum transforms the place-coded retinal information into rate-coded turning commands in the reticulospinal neurons via a recruitment network mimicking the layered structure of tectal areas. Via engagement of the basal ganglia, the system proves to be capable of selecting among several possible responses, even if exposed to conflicting stimuli. The anatomically based structure of the control system makes it possible to disconnect different neural components, yielding concrete predictions of how animals with corresponding lesions would behave. The model confirms that the neural networks identified in the lamprey are capable of responding appropriately to simple, multiple, and conflicting stimuli.

  • 95.
    Kaplan, Bernhard
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Anders, Lansner
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Perrinet, Laurent
    Centre National de la Recherche Scientifique & Aix-Marseille Université, Marseille, France.
    Masson, Guillaume
    Centre National de la Recherche Scientifique & Aix-Marseille Université, Marseille, France.
    Anisotropic connectivity implements motion-basedprediction in a spiking neural network2013In: Frontiers in Computational Neuroscience, ISSN 1662-5188, E-ISSN 1662-5188Article in journal (Refereed)
    Abstract [en]

    Predictive coding hypothesizes that the brain explicitly infers upcoming sensory inputto establish a coherent representation of the world. Although it is becoming generallyaccepted, it is not clear on which level spiking neural networks may implementpredictive coding and what function their connectivity may have. We present a networkmodel of conductance-based integrate-and-fire neurons inspired by the architectureof retinotopic cortical areas that assumes predictive coding is implemented throughnetwork connectivity, namely in the connection delays and in selectiveness for the tuningproperties of source and target cells. We show that the applied connection pattern leadsto motion-based prediction in an experiment tracking a moving dot. In contrast to ourproposed model, a network with random or isotropic connectivity fails to predict the pathwhen the moving dot disappears. Furthermore, we show that a simple linear decodingapproach is sufficient to transform neuronal spiking activity into a probabilistic estimatefor reading out the target trajectory.

  • 96. Khoonsari, Payam Emami
    et al.
    Häggmark, Anna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lonnberg, Maria
    Mikus, Maria
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kilander, Lena
    Lannfelt, Lars
    Bergquist, Jonas
    Ingelsson, Martin
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Shevchenko, Ganna
    Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0150672Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer's disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer's disease patients and non-demented controls to identify potential biomarkers for Alzheimer's disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer's disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer's disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system.

  • 97. Kirbis, M.
    et al.
    Morrison, S.
    Rojc, B.
    Eiken, Ola
    KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Environmental Physiology.
    Igor, M.
    Groselj, L. Dolenc
    Hypoxia and bedrest progressively attenuate parasympathetic activity during sleep2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, p. 236-237Article in journal (Other academic)
  • 98.
    Kisner, Alexandre
    et al.
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Slocomb, Julia E.
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Sarsfield, Sarah
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Zuccoli, Maria Laura
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.;Univ Genoa, Dept Internal Med, Pharmacol & Toxicol Unit, Genoa, Italy..
    Siemian, Justin
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Gupta, Jay F.
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Kumar, Arvind
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST).
    Aponte, Yeka
    NIDA, Neuronal Circuits & Behav Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.;Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA..
    Electrophysiological properties and projections of lateral hypothalamic parvalbumin positive neurons2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0198991Article in journal (Refereed)
    Abstract [en]

    Cracking the cytoarchitectural organization, activity patterns, and neurotransmitter nature of genetically-distinct cell types in the lateral hypothalamus (LH) is fundamental to develop a mechanistic understanding of how activity dynamics within this brain region are generated and operate together through synaptic connections to regulate circuit function. However, the precise mechanisms through which LH circuits orchestrate such dynamics have remained elusive due to the heterogeneity of the intermingled and functionally distinct cell types in this brain region. Here we reveal that a cell type in the mouse LH identified by the expression of the calcium-binding protein parvalbumin (PVALB; LHPV) is fast-spiking, releases the excitatory neurotransmitter glutamate, and sends long range projections throughout the brain. Thus, our findings challenge long-standing concepts that define neurons with a fast-spiking phenotype as exclusively GABAergic. Furthermore, we provide for the first time a detailed characterization of the electrophysiological properties of these neurons. Our work identifies LHPV neurons as a novel functional component within the LH glutamatergic circuitry.

  • 99. Kleber, Boris
    et al.
    Zeitouni, Anthony G.
    Friberg, Anders
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Zatorre, Robert J.
    Experience-Dependent Modulation of Feedback Integration during Singing: Role of the Right Anterior Insula2013In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, no 14, p. 6070-6080Article in journal (Refereed)
    Abstract [en]

    Somatosensation plays an important role in the motor control of vocal functions, yet its neural correlate and relation to vocal learning is not well understood. We used fMRI in 17 trained singers and 12 nonsingers to study the effects of vocal-fold anesthesia on the vocal-motor singing network as a function of singing expertise. Tasks required participants to sing musical target intervals under normal conditions and after anesthesia. At the behavioral level, anesthesia altered pitch accuracy in both groups, but singers were less affected than nonsingers, indicating an experience-dependent effect of the intervention. At the neural level, this difference was accompanied by distinct patterns of decreased activation in singers (cortical and subcortical sensory and motor areas) and nonsingers (subcortical motor areas only) respectively, suggesting that anesthesia affected the higher-level voluntary (explicit) motor and sensorimotor integration network more in experienced singers, and the lower-level (implicit) subcortical motor loops in nonsingers. The right anterior insular cortex (AIC) was identified as the principal area dissociating the effect of expertise as a function of anesthesia by three separate sources of evidence. First, it responded differently to anesthesia in singers (decreased activation) and nonsingers (increased activation). Second, functional connectivity between AIC and bilateral A1, M1, and S1 was reduced in singers but augmented in nonsingers. Third, increased BOLD activity in right AIC in singers was correlated with larger pitch deviation under anesthesia. We conclude that the right AIC and sensory-motor areas play a role in experience-dependent modulation of feedback integration for vocal motor control during singing.

  • 100.
    Kosterina, Natalia
    et al.
    KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Wang, Ruoli
    KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Eriksson, Anders
    KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Gutierrez Farewik, Lanie
    KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Force enhancement and force depression in a modified muscle model used for muscle activation prediction2013In: Journal of Electromyography & Kinesiology, ISSN 1050-6411, E-ISSN 1873-5711, Vol. 23, no 4, p. 759-765Article in journal (Refereed)
    Abstract [en]

    This article introduces history-dependent effects in a skeletal muscle model applied to dynamic simulations of musculoskeletal system motion. Force depression and force enhancement induced by active muscle shortening and lengthening, respectively, represent muscle history effects. A muscle model depending on the preceding contractile events together with the current parameters was developed for OpenSim software, and applied in simulations of standing heel-raise and squat movements. Muscle activations were computed using joint kinematics and ground reaction forces recorded from the motion capture of seven individuals. In the muscle-actuated simulations, a modification was applied to the computed activation, and was compared to the measured electromyography data. For the studied movements, the history gives a small but visible effect to the muscular force trace, but some parameter values must be identified before the exact magnitude can be analysed. The muscle model modification improves the existing muscle models and gives a more accurate description of underlying forces and activations in musculoskeletal system movement simulations.

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