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  • 1.
    Ayoglu, Burcu
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Kockum, Ingrid
    Olsson, Tomas
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Anoctamin 2 identified as an autoimmune target in multiple sclerosis2016In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 10-10Article in journal (Other academic)
  • 2.
    Blom, Hans
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bernhem, Kristoffer
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Sodium pump organization in dendritic spines2016In: NEUROPHOTONICS, ISSN 2329-423X, Vol. 3, no 4, article id 041803Article in journal (Refereed)
    Abstract [en]

    Advancement in fluorescence imaging with the invention of several super-resolution microscopy modalities (e.g., PALM/STORM and STED) has opened up the possibility of deciphering molecular distributions on the nanoscale. In our quest to better elucidate postsynaptic protein distribution in dendritic spines, we have applied these nanoscopy methods, where generated results could help improve our understanding of neuronal functions. In particular, we have investigated the principal energy transformer in the brain, i.e., the Na+; K+-ATPase (or sodium pump), an essential protein responsible for maintaining resting membrane potential and a major controller of intracellular ion homeostasis. In these investigations, we have focused on estimates of protein amount, giving assessments of how variations may depend on labeling strategies, sample analysis, and choice of nanoscopic imaging method, concluding that all can be critical factors for quantification. We present a comparison of these results and discuss the influences this may have for homeostatic sodium regulation in neurons and energy consumption.

  • 3. Crook, S. M.
    et al.
    Bednar, J. A.
    Berger, S.
    Cannon, R.
    Davison, A. P.
    Djurfeldt, Mikael
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Eppler, J.
    Kriener, B.
    Furber, S.
    Graham, B.
    Plesser, H. E.
    Schwabe, L.
    Smith, L.
    Steuber, V.
    Van Albada, S.
    Creating, documenting and sharing network models2012In: Network, ISSN 0954-898X, E-ISSN 1361-6536, Vol. 23, no 4, p. 131-149Article, review/survey (Refereed)
    Abstract [en]

    As computational neuroscience matures, many simulation environments are available that are useful for neuronal network modeling. However, methods for successfully documenting models for publication and for exchanging models and model components among these projects are still under development. Here we briefly review existing software and applications for network model creation, documentation and exchange. Then we discuss a few of the larger issues facing the field of computational neuroscience regarding network modeling and suggest solutions to some of these problems, concentrating in particular on standardized network model terminology, notation, and descriptions and explicit documentation of model scaling. We hope this will enable and encourage computational neuroscientists to share their models more systematically in the future.

  • 4. Damangir, Soheil
    et al.
    Manzouri, Amirhossein
    Oppedal, Ketil
    Carlsson, Stefan
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Firbank, Michael J.
    Sonnesyn, Hogne
    Tysnes, Ole-Bjorn
    O'Brien, John T.
    Beyer, Mona K.
    Westman, Eric
    Aarsland, Dag
    Wahlund, Lars-Olof
    Spulber, Gabriela
    Multispectral MRI segmentation of age related white matter changes using a cascade of support vector machines2012In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 322, no 1-2, p. 211-216Article in journal (Refereed)
    Abstract [en]

    White matter changes (WMC) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMC labor intensive and prone to subjective bias. We present a fast, fully automated method for WMC segmentation using a cascade of reduced support vector machines (SVMs) with active learning. Data of 102 subjects was used in this study. Two MRI sequences (T1-weighted and FLAIR) and masks of manually outlined WMC from each subject were used for the image analysis. The segmentation framework comprises pre-processing, classification (training and core segmentation) and post-processing. After pre-processing, the model was trained on two subjects and tested on the remaining 100 subjects. The effectiveness and robustness of the classification was assessed using the receiver operating curve technique. The cascade of SVMs segmentation framework outputted accurate results with high sensitivity (90%) and specificity (99.5%) values, with the manually outlined WMC as reference. An algorithm for the segmentation of WMC is proposed. This is a completely competitive and fast automatic segmentation framework, capable of using different input sequences, without changes or restrictions of the image analysis algorithm.

  • 5. Ercole, A.
    et al.
    Thelin, E. P.
    Holst, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Bellander, B. M.
    Nelson, D. W.
    Kinetic modelling of serum S100b after traumatic brain injury2016In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 16, article id 93Article in journal (Refereed)
    Abstract [en]

    Background: An understanding of the kinetics of a biomarker is essential to its interpretation. Despite this, little kinetic modelling of blood biomarkers can be found in the literature. S100b is an astrocyte related marker of brain injury used primarily in traumatic brain injury (TBI). Serum levels are expected to be the net result of a multi-compartmental process. The optimal sample times for TBI prognostication, and to follow injury development, are unclear. The purpose of this study was to develop a kinetic model to characterise the temporal course of serum S100b concentration after primary traumatic brain injury. Methods: Data of serial serum S100b samples from 154 traumatic brain injury patients in a neurointensive care unit were retrospectively analysed, including only patients without secondary peaks of this biomarker. Additionally, extra-cranial S100b can confound samples earlier than 12 h after trauma and were therefore excluded. A hierarchical, Bayesian gamma variate kinetic model was constructed and the parameters estimated by Markov chain Monte Carlo sampling. Results: We demonstrated that S100b concentration changes dramatically over timescales that are clinically important for early prognostication with a peak at 27.2 h (95 % credible interval [25.6, 28.8]). Baseline S100b levels was found to be 0.11 mu g/L (95 % credible interval [0.10, 0.12]). Conclusions: Even small differences in injury to sample time may lead to marked changes in S100b during the first days after injury. This must be taken into account in interpretation. The model offers a way to predict the peak and trajectory of S100b from 12 h post trauma in TBI patients, and to identify deviations from this, possibly indicating a secondary event. Kinetic modelling, providing an equation for the peak and projection, may offer a way to reduce the ambiguity in interpretation of, in time, randomly sampled acute biomarkers and may be generally applicable to biomarkers with, in time, well defined hits.

  • 6.
    Farewik, Lanie
    KTH, School of Engineering Sciences (SCI), Mechanics, Biomechanics. University of Michigan, Department of Mechanical Engineering, Division of Biomechanics.
    Mild diabetic neuropathy affects ankle motor function2001In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 16, no 6, p. 522-528Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the effect of age and diabetic neuropathy on ankle motor function in the frontal plane in terms of rate of torque development and capability for balance recovery.

    Design. Case control study. Six older women with diabetic neuropathy compared to six women without neuropathy, matched for age and presence of diabetes mellitus; and nine healthy young women.

    Background. Neuropathy causes a distal impairment in lower extremity sensory function which increases fall risk. Impairments in ankle inversion/eversion proprioceptive thresholds have been identified, but the effect of neuropathy on ankle motor strength in the frontal plane is unknown.

    Methods. Subjects' abilities to recover from a lateral lean (with center of gravity offset as percentage of foot width) while standing on one foot, and to rapidly generate inversion torque about the ankle, were quantified.

    Results. All nine of the young, but only one of six older, control subjects recovered from a 10% lean (P=0.0052). Three of six older controls, but no neuropathy subject, recovered from a 5% lean (P=0.083). Neuropathy subjects demonstrated half the ankle rate of torque development [78.2 (50.8) N m/s; P=0.016] of the young and older controls [162.0 (54.6) and 152.7 (22.2) N m/s, respectively].

    Conclusions. Diabetic neuropathy leads to a decrease in rapidly available ankle strength which impairs balance recovery among older women. Younger women demonstrate similar ankle strength but superior balance recovery compared to older women without neuropathy.Relevance

    Older women with diabetic neuropathy and normal ankle strength, as judged by clinical muscle testing, demonstrate a sub-clinical impairment in ankle motor function suggesting a target for intervention.

  • 7.
    Fiebig, Florian
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Lansner, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Memory consolidation from seconds to weeks: a three-stage neural network model with autonomous reinstatement dynamics2014In: Frontiers in Computational Neuroscience, ISSN 1662-5188, E-ISSN 1662-5188, Vol. 8, p. 64-Article in journal (Refereed)
    Abstract [en]

    Declarative long-term memories are not created in an instant. Gradual stabilization and temporally shifting dependence of acquired declarative memories in different brain regions called systems consolidation- can be tracked in time by lesion experiments. The observation of temporally graded retrograde amnesia(RA) following hippocampal lesions points to a gradual transfer of memory from hippocampus to neocortical long-term memory. Spontaneous reactivations of hippocampal memories, asobserved in place cell reactivations during slow wave- sleep, are supposed to driven eocortical reinstatements and facilitate this process. We proposea functional neural network implementation of these ideas and further more suggest anextended three-state framework that includes the prefrontal cortex( PFC). It bridges the temporal chasm between working memory percepts on the scale of seconds and consolidated long-term memory on the scale of weeks or months. Wes how that our three-stage model can autonomously produce the necessary stochastic reactivation dynamics for successful episodic memory consolidation. There sulting learning system is shown to exhibit classical memory effects seen in experimental studies, such as retrograde and anterograde amnesia(AA) after simulated hippocampal lesioning; further more the model reproduces peculiar biological findings on memory modulation, such as retrograde facilitation of memory after suppressed acquisition of new longterm memories- similar to the effects of benzodiazepines on memory.

  • 8.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Ionic Mechanisms in Peripheral Pain2014In: Computational Neuroscience / [ed] Blackwell, K.T., Elsevier, 2014, p. 23-51Chapter in book (Refereed)
    Abstract [en]

    Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs.

  • 9.
    Fransén, Erik A.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Mechanisms of Graded Persistent Activity: Implications for Epilepsy2008In: Computational Neuroscience in Epilepsy, Elsevier, 2008, p. 215-231Chapter in book (Other academic)
    Abstract [en]

    One major topic in epilepsy is factors contributing to neuronal excitability. This chapter considers depolarizing sources from cationic currents. These ion channels of the TRP-type are permeable to Na, K and sometimes Ca, and show a slow time dynamics. They can therefore provide the dendrites with integrative properties over seconds and perhaps even minutes. This makes them powerful as integrators of synaptic input. Further, their activation depends to a large degree on intracellular calcium. They may therefore during seizures become strongly activated and thereby further contribute to epileptogenic activity directly by depolarization and indirectly by their calcium permeability. Cationic currents are widely distributed throughout the nervous system, including cortical, cerebellar and subcortical neurons. This chapter describes the work in entorhinal cortex and, specifically, the plateau firing characteristics found in pyramidal cells of layer V. These cells show persistent action potential firing at plateaus, which may last over ten minutes. Intriguingly, these plateaus are graded in that input, synaptic or by current injection, can shift them up and down in frequency. After the original finding, graded plateaus have been found also in perirhinal cortex and amygdala. Functionally, cationic neuronal integrator capacity has been shown to be involved in sensory-motor integration. Finally, anticonvulsants like lamotrigine and phenytoin have been found to reduce depolarizations involving cationic currents. Cation currents may therefore be targets in treatments of epilepsy.

  • 10.
    Frykberg, Gunilla
    et al.
    Uppsala University.
    Åberg, Anna Cristina
    The Swedish School of Sport and Health Sciences.
    Halvorsen, Kjartan
    The Swedish School of Sports and Health Sciences.
    Hirschfeld, Helga
    Karolinska Institute.
    Temporal characteristics of the sit-to-walk task in subjects with stroke and in controls: Preliminary results2007In: Proceedings of the 16th annual meeting of ESMAC, 2007Conference paper (Refereed)
  • 11. Graham, C.
    et al.
    Lewis, S.
    Forbes, J.
    Mead, G.
    Hackett, M. L.
    Hankey, G. J.
    Gommans, J.
    Nguyen, H. T.
    Lundström, E.
    Isaksson, E.
    Näsman, Per
    KTH.
    Rudberg, A. -S
    Dennis, M.
    The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: Statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis2017In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 18, no 1, article id 627Article in journal (Refereed)
    Abstract [en]

    Background: Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. Methods/Design: The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Discussion: Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020.

  • 12. Gustafsson, J.
    et al.
    Ternström, Sten
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Södersten, M.
    Schalling, E.
    Motor-Learning-Based Adjustment of Ambulatory Feedback on Vocal Loudness for Patients With Parkinson's Disease2016In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, no 4, p. 407-415Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate how the direct biofeedback on vocal loudness administered with a portable voice accumulator (VoxLog) should be configured, to facilitate an optimal learning outcome for individuals with Parkinson's disease (PD), on the basis of principles of motor learning. Study Design: Methodologic development in an experimental study. Methods: The portable voice accumulator VoxLog was worn by 20 participants with PD during habitual speech during semistructured conversations. Six different biofeedback configurations were used, in random order, to study which configuration resulted in a feedback frequency closest to 20% as recommended on the basis of previous studies. Results: Activation of feedback when the wearer speaks below a threshold level of 3dB below the speaker's mean voice sound level in habitual speech combined with an activation time of 500ms resulted in a mean feedback frequency of 21.2%. Conclusions: Settings regarding threshold and activation time based on the results from this study are recommended to achieve an optimal learning outcome when administering biofeedback on vocal loudness for individuals with PD using portable voice accumulators.

  • 13. Hernandez, F.
    et al.
    Wu, L. C.
    Yip, M. C.
    Hoffman, A. R.
    Lopez, J.
    Grant, G.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Camarillo, D. B.
    Finite Element Simulation Of Brain Deformation From Six Degree Of Freedom Acceleration Measurements Of Mild Traumatic Brain Injury2014In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, no 12, p. A124-A124Article in journal (Other academic)
  • 14. James, T.
    et al.
    Linden, M.
    Huss, M.
    Brandi, Maya
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Khademi, M.
    Tegner, J.
    Gomez-Cabrero, D.
    Kockum, I.
    Olsson, T.
    Impact of genetic risk loci in multiple sclerosis on expression of proximal genes2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, p. 250-251Article in journal (Other academic)
  • 15.
    Kaplan, Bernhard A.
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Lansner, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system2014In: Frontiers in Neural Circuits, ISSN 1662-5110, E-ISSN 1662-5110, Vol. 8, no Feb, p. 5-Article in journal (Refereed)
    Abstract [en]

    Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin-Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian-Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian-Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures.

  • 16.
    Karlsson, Bengt
    et al.
    Natl Univ Singapore Hosp, Div Neurosurg, Dept Surg, Singapore, Singapore..
    Johansson, Arne V.
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Yang, Huai-Che
    Vet Gen Hosp, Dept Neurosurg, Taipei, Taiwan..
    Jokura, Hidefumi
    Furukawa Seiryo Hosp, Jiro Suzuki Mem Gamma House, Osaki, Japan..
    Yamamoto, Masaaki
    Katsuta Hosp Mito GammaHouse, Ibaraki, Japan..
    Martinez-Alvarez, Roberto
    Ruber Int Hosp, Madrid, Spain..
    Kawagishi, Jun
    Furukawa Seiryo Hosp, Jiro Suzuki Mem Gamma House, Osaki, Japan..
    Guo, Wan-Yuo
    Vet Gen Hosp, Dept Radiol, Taipei, Taiwan..
    Beute, Guus
    ETZ Elizabeth, Tilburg, Netherlands..
    Pan, David H. C.
    Vet Gen Hosp, Dept Neurosurg, Taipei, Taiwan..
    Chung, Wen-Yuh
    Vet Gen Hosp, Dept Neurosurg, Taipei, Taiwan.;Vet Gen Hosp, Dept Radiol, Taipei, Taiwan..
    Soderman, Michael
    Karolinska Hosp, Stockholm, Sweden..
    Aiyama, Hitoshi
    Katsuta Hosp Mito GammaHouse, Ibaraki, Japan..
    Yeo, Tseng Tsai
    Natl Univ Singapore Hosp, Div Neurosurg, Dept Surg, Singapore, Singapore..
    A novel method to determine the natural course of unruptured brain arteriovenous malformations without the need for follow-up information2018In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 129, p. 10-16Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE There is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture. METHODS The present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy. RESULTS The age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25-60 years). It was concluded to be 3.1% +/- 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years. CONCLUSIONS The present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% +/- 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.

  • 17. Kavaliunas, Andrius
    et al.
    Manouchehrinia, Ali
    Stawiarz, Leszek
    Ramanujam, Ryan
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Mathematics (Div.).
    Agholme, Jonas
    Hedstrom, Anna Karin
    Beiki, Omid
    Glaser, Anna
    Hillert, Jan
    Importance of early treatment initiation in the clinical course of multiple sclerosis2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 9, p. 1233-1240Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment decisions influence outcome. Methods: We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years). Cox regression models were applied to identify factors correlating with the outcome variable defined as time from treatment start to irreversible score 4 of the Expanded Disability Status Scale (EDSS). Results: Patients initiated on treatment later had a greater risk of reaching EDSS 4 (hazard ratio of 1.074 (95% confidence interval (CI), 1.048-1.101)), increased by 7.4% for every year of delay in treatment start after MS onset. Patients who started treatment after 3 years from MS onset reached the outcome sooner with hazard ratio of 2.64 (95% CI, 1.71-4.08) compared with the patients who started treatment within 1 year from MS onset. Baseline EDSS and age at onset were found to be predictive factors of disability progression. Conclusion: Early treatment initiation was associated with a better clinical outcome. In addition, we confirmed the well-established prognostic factors of late age at onset and early disability.

  • 18. Keimpema, Erik
    et al.
    Zheng, Kang
    Barde, Swapnali Shantaram
    Berghuis, Paul
    Dobszay, Marton B.
    Schnell, Robert
    Mulder, Jan
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institute, Sweden.
    Luiten, Paul G. M.
    Xu, Zhiqing David
    Runesson, Johan
    Langel, Ulo
    Lu, Bai
    Hökfelt, Tomas
    Harkany, Tibor
    GABAergic Terminals Are a Source of Galanin to Modulate Cholinergic Neuron Development in the Neonatal Forebrain2014In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 24, no 12, p. 3277-3288Article in journal (Refereed)
    Abstract [en]

    The distribution and (patho-) physiological role of neuropeptides in the adult and aging brain have been extensively studied. Galanin is an inhibitory neuropeptide that can coexist with.-aminobutyric acid (GABA) in the adult forebrain. However, galanin's expression sites, mode of signaling, impact on neuronal morphology, and colocalization with amino acid neurotransmitters during brain development are less well understood. Here, we show that galaninergic innervation of cholinergic projection neurons, which preferentially express galanin receptor 2 (GalR2) in the neonatal mouse basal forebrain, develops by birth. Nerve growth factor (NGF), known to modulate cholinergic morphogenesis, increases GalR2 expression. GalR2 antagonism (M871) in neonates reduces the in vivo expression and axonal targeting of the vesicular acetylcholine transporter (VAChT), indispensable for cholinergic neurotransmission. During cholinergic neuritogenesis in vitro, GalR2 can recruit Rho-family GTPases to induce the extension of a VAChT-containing primary neurite, the prospective axon. In doing so, GalR2 signaling dose-dependently modulates directional filopodial growth and antagonizes NGF-induced growth cone differentiation. Galanin accumulates in GABA-containing nerve terminals in the neonatal basal forebrain, suggesting its contribution to activity-driven cholinergic development during the perinatal period. Overall, our data define the cellular specificity and molecular complexity of galanin action in the developing basal forebrain.

  • 19.
    Khoonsari, Payam Emami
    et al.
    Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden..
    Shevchenko, Ganna
    Uppsala Univ, Dept Chem BMC, Analyt Chem, Uppsala, Sweden..
    Herman, Stephanie
    Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden..
    Remnestål, Julia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Giedraitis, Vilmantas
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden..
    Brundin, RoseMarie
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden..
    Gunnarsson, Malin Degerman
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden..
    Kilander, Lena
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden..
    Zetterberge, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UK Dementia Res Inst UCL, London, England.;UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lannfelt, Lars
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden..
    Ingelsson, Martin
    Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden..
    Kultima, Kim
    Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden..
    Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 2, p. 639-651Article in journal (Refereed)
    Abstract [en]

    Background: Alzheimer's disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: A beta(42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. Objective: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. Methods: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4-9 years and 21 of these converted to AD, whereas 53 remained stable. Results: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCl/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. Conclusions: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.

  • 20.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Predictors for Traumatic Brain Injuries Evaluated through Accident Reconstructions2007In: Stapp Car Crash Journal, ISSN 1532-8546, Vol. 51, p. 81-114Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to evaluate all the 58 available NFL cases and compare various predictors for mild traumatic brain injuries using a detailed and extensively validated finite element model of the human head. Global injury measures such as magnitude in angular and translational acceleration, change in angular velocity, head impact power (HIP) and HIC were also investigated with regard to their ability to predict the intracranial pressure and strains associated with injury. The brain material properties were modeled using a hyperelastic and viscoelastic constitutive law. Also, three different stiffness parameters, encompassing a range of published brain tissue properties, were tested. 8 tissue injury predictors were evaluated for 6 different regions, covering the entire cerebrum, as well as for the whole brain. In addition, 10 head kinematics based predictors were evaluated both for correlation with injury as well as with strain and pressure. When evaluating the results, a statistical correlation between strain, strain rate, product of strain and strain rate, Cumulative Strain Damage Measure (CSDM), strain energy density, maximum pressure, magnitude of minimum pressure, as well as von Mises effective stress, with injury was found when looking into specific regions of the brain. However, the maximal pressure in the gray matter showed a higher correlation with injury than other evaluated measures. On the other hand, it was possible, through the reconstruction of a motocross accident, to re-create the injury pattern in the brain of the injured rider using maximal principal strain. It was also found that a simple linear combination of peak change in rotational velocity and HIC showed a high correlation (R=0.98) with the maximum principal strain in the brain, in addition to being a significant predictor of injury. When applying the rotational and translational kinematics separately for one of the cases, it was found that the translational kinematics contribute very little to the intracranial distortional strains while the rotational kinematics contributes insignificantly to the pressure response. This study underlines that the strain based brain tissue injury predictors are very sensitive to the choice of stiffness for the brain tissue.

  • 21.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    The biomechanics of ‘real’ head protection: New thoughts on preventing TBI2008Conference paper (Other academic)
  • 22.
    Kroon, Martin
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Simulation of cerebral aneurysm growth and prediction of evolving rupture risk2011In: Modelling and Simulation in Engineering, ISSN 1687-5591, Vol. 2011, p. 289523-Article in journal (Refereed)
    Abstract [en]

    Cerebral aneurysms are local expansions of blood vessel walls in the brain blood system. The rupture of an aneurysm is a very severe event associated with a high rate of mortality. When cerebral aneurysms are detected, clinicians need to decide if operation is required. The risk of aneurysm rupture is then compared to the risks associated with the medical intervention. In the present paper, a probabilistic framework for a mechanically based rupture risk assessment of cerebral aneurysms is proposed. The method is based on the assumption that the strength of aneurysmal tissues can be described by a statistical distribution. A structural analysis of the aneurysm in question is performed, and the maximum stress experienced by the aneurysm is compared to the strength distribution. The proposed model was compared with clinical results for ruptured aneurysms in terms of rupture density and accumulated rupture risk as a function of aneurysm size. The model was able to reproduce the clinical results well. The proposed framework may potentially be used under in vivo conditions to predict the risk of rupture for diagnosed aneurysms.

  • 23. Larhammar, Martin
    et al.
    Patra, Kalicharan
    Blunder, Martina
    Emilsson, Lina
    Peuckert, Christiane
    Arvidsson, Emma
    Rönnlund, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Preobraschenski, Julia
    Birgner, Carolina
    Limbach, Christoph
    Widengren, Jerker
    Blom, Hans
    Jahn, Reinhard
    Wallen-Mackenzie, Asa
    Kullander, Klas
    SLC10A4 Is a Vesicular Amine-Associated Transporter Modulating Dopamine Homeostasis2015In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 77, no 6, p. 526-536Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The neuromodulatory transmitters, biogenic amines, have profound effects on multiple neurons and are essential for normal behavior and mental health. Here we report that the orphan transporter SLC10A4, which in the brain is exclusively expressed in presynaptic vesicles of monoaminergic and cholinergic neurons, has a regulatory role in dopamine homeostasis. METHODS: We used a combination of molecular and behavioral analyses, pharmacology, and in vivo amperometry to assess the role of SLC10A4 in dopamine- regulated behaviors. RESULTS: We show that SLC10A4 is localized on the same synaptic vesicles as either vesicular acetylcholine transporter or vesicular monoamine transporter 2. We did not find evidence for direct transport of dopamine by SLC10A4; however, synaptic vesicle preparations lacking SLC10A4 showed decreased dopamine vesicular uptake efficiency. Furthermore, we observed an increased acidification in synaptic vesicles isolated from mice over-expressing SLC10A4. Loss of SLC10A4 in mice resulted in reduced striatal serotonin, noradrenaline, and dopamine concentrations and a significantly higher dopamine turnover ratio. Absence of SLC10A4 led to slower dopamine clearance rates in vivo, which resulted in accumulation of extracellular dopamine. Finally, whereas SLC10A4 null mutant mice were slightly hypoactive, they displayed hypersensitivity to administration of amphetamine and tranylcypromine. CONCLUSIONS: Our results demonstrate that SLC10A4 is a vesicular monoaminergic and cholinergic associated transporter that is important for dopamine homeostasis and neuromodulation in vivo. The discovery of SLC10A4 and its role in dopaminergic signaling reveals a novel mechanism for neuromodulation and represents an unexplored target for the treatment of neurological and mental disorders.

  • 24.
    Leng, Yan
    et al.
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Wang, Zhu
    Sun Yat Sen Univ, Inst Diagnost & Intervent Ultrasound, Affiliated Hosp 1, Dept Med Ultrason, Guangzhou, Guangdong, Peoples R China..
    Bian, Ruihao
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Lo, Wai Leung Ambrose
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Xie, Xiaoyan
    Sun Yat Sen Univ, Inst Diagnost & Intervent Ultrasound, Affiliated Hosp 1, Dept Med Ultrason, Guangzhou, Guangdong, Peoples R China..
    Wang, Ruoli
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, BioMEx. Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Huang, Dongfeng
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China.;Sun Yat Sen Univ, Affiliated Hosp 7, Dept Rehabil Med, Shenzhen, Peoples R China..
    Li, Le
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rehabil Med, Guangzhou, Guangdong, Peoples R China..
    Alterations of Elastic Property of Spastic Muscle With Its Joint Resistance Evaluated From Shear Wave Elastography and Biomechanical Model2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 736Article in journal (Refereed)
    Abstract [en]

    This study aims to quantify passive muscle stiffness of spastic wrist flexors in stroke survivors using shear wave elastography (SWE) and to correlate with neural and non-neural contributors estimated from a biomechanical model to hyper-resistance measured during passive wrist extension. Fifteen hemiplegic individuals after stroke with Modified Ashworth Scale (MAS) score larger than one were recruited. SWE were used to measure Young's modulus of flexor carpi radialis muscle with joint from 0 degrees (at rest) to 50 degrees flexion (passive stretch condition), with 10 degrees interval. The neural (NC) and non-neural components i.e., elasticity component (EC) and viscosity component (VC) of the wrist joint were analyzed from a motorized mechanical device NeuroFlexor (R) (NF). Combining with a validated biomechanical model, the neural reflex and muscle stiffness contribution to the increased resistance can be estimated. MAS and Fugl-Meyer upper limb score were also measured to evaluate the spasticity and motor function of paretic upper limb. Young's modulus was significantly higher in the paretic side of flexor carpi radialis than that of the non-paretic side (p < 0.001) and it increased significantly from 0 degrees to 50 degrees of the paretic side (p < 0.001). NC, EC, and VC on the paretic side were higher than the non-paretic side (p < 0.05). There was moderate significant positive correlation between the Young's Modulus and EC (r = 0.565, p = 0.028) and VC (r = 0.645, p = 0.009) of the paretic forearm flexor muscle. Fugl-Meyer of the paretic forearm flexor has a moderate significant negative correlation with NC (r = -0.578, p = 0.024). No significant correlation between MAS and shear elastic modulus or NF components was observed. This study demonstrated the feasibility of combining SWE and NF as a non-invasive approach to assess spasticity of paretic muscle and joint in stroke clinics. The neural and non-neural components analysis as well as correlation findings of muscle stiffness of SWE might provide understanding of mechanism behind the neuromuscular alterations in stroke survivors and facilitate the design of suitable intervention for them.

  • 25. Li, Fang
    et al.
    Zhu, Huilin
    Xu, Jie
    Gao, Qianqian
    Guo, Huan
    Wu, Shijing
    Li, Xinge
    He, Sailing
    KTH, School of Electrical Engineering and Computer Science (EECS), Electromagnetic Engineering.
    Lie Detection Using fNIRS Monitoring of Inhibition-Related Brain Regions Discriminates Infrequent but not Frequent Liars2018In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 12, article id 71Article in journal (Refereed)
    Abstract [en]

    Functional near-infrared spectroscopy (fNIRS) was used to test whether monitoring inhibition-related brain regions is a feasible method for detecting both infrequent liars and frequent liars. Thirty-two participants were divided into two groups: the deceptive group (liars) and the non-deceptive group (ND group, innocents). All the participants were required to undergo a simulated interrogation by a computer. The participants from the deceptive group were instructed to tell a mix of lies and truths and those of the ND group were instructed always to tell the truth. Based on the number of deceptions, the participants of the deceptive group were further divided into a infrequently deceptive group (IFD group, infrequent liars) and a frequently deceptive group (FD group, frequent liars). The infrequent liars exhibited greater neural activities than the frequent liars and the innocents in the left middle frontal gyrus (MFG) when performing the deception detection tasks. While performing deception detection tasks, infrequent liars showed significantly greater neural activation in the left MFG than the baseline, but frequent liars and innocents did not exhibit this pattern of neural activation in any area of inhibition-related brain regions. The results of individual analysis showed an acceptable accuracy of detecting infrequent liars, but an unacceptable accuracy of detecting frequent liars. These results suggest that using fNIRS monitoring of inhibition-related brain regions is feasible for detecting infrequent liars, for whom deception may be more effortful and therefore more physiologically marked, but not frequent liars.

  • 26. Lindroos, Robert
    et al.
    Dorst, Matthijs C.
    Du, Kai
    Filipovic, Marko
    Keller, Daniel
    Ketzef, Maya
    Kozlov, Alexander K.
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kumar, Arvind
    Lindahl, Mikael
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nair, Anu G.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Perez-Fernandez, Juan
    Grillner, Sten
    Silberberg, Gilad
    Hällgren Kotaleski, Jeanette
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales-Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.22018In: Frontiers in Neural Circuits, ISSN 1662-5110, E-ISSN 1662-5110, Vol. 12, article id 3Article in journal (Refereed)
    Abstract [en]

    The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level dopaminergic effects. In particular we predict dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical aspects of the onset of neuromodulation effects in multi-scale computational models combining biochemical signaling cascades and multi-compartmental neuron models.

  • 27.
    Lundqvist, Mikael
    et al.
    MIT, Picower Inst Learning & Memory, 43 Vassar St, Cambridge, MA 02139 USA.;MIT, Dept Brain & Cognit Sci, 43 Vassar St, Cambridge, MA 02139 USA..
    Herman, Pawel
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST).
    Miller, Earl K.
    MIT, Picower Inst Learning & Memory, 43 Vassar St, Cambridge, MA 02139 USA.;MIT, Dept Brain & Cognit Sci, 43 Vassar St, Cambridge, MA 02139 USA..
    Working Memory: Delay Activity, Yes! Persistent Activity? Maybe Not2018In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 38, no 32, p. 7013-7019Article in journal (Refereed)
    Abstract [en]

    Persistent spiking has been thought to underlie working memory (WM). However, virtually all of the evidence for this comes from studies that averaged spiking across time and across trials, which masks the details. On single trials, activity often occurs in sparse transient bursts. This has important computational and functional advantages. In addition, examination of more complex tasks reveals neural coding in WM is dynamic over the course of a trial. All this suggests that spiking is important for WM, but that its role is more complex than simply persistent spiking.

  • 28. Lundqvist, Mikael
    et al.
    Rose, Jonas
    Herman, Pawel
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Brincat, Scott L.
    Buschman, Timothy J.
    Miller, Earl K.
    Gamma and Beta Bursts Underlie Working Memory2016In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 90, no 1, p. 152-164Article in journal (Refereed)
    Abstract [en]

    Working memory is thought to result from sustained neuron spiking. However, computational models suggest complex dynamics with discrete oscillatory bursts. We analyzed local field potential (LFP) and spiking from the prefrontal cortex (PFC) of monkeys performing a working memory task. There were brief bursts of narrow-band gamma oscillations (45-100 Hz), varied in time and frequency, accompanying encoding and re-activation of sensory information. They appeared at a minority of recording sites associated with spiking reflecting the to-be-remembered items. Beta oscillations (20-35 Hz) also occurred in brief, variable bursts but reflected a default state interrupted by encoding and decoding. Only activity of neurons reflecting encoding/decoding correlated with changes in gamma burst rate. Thus, gamma bursts could gate access to, and prevent sensory interference with, working memory. This supports the hypothesis that working memory is manifested by discrete oscillatory dynamics and spiking, not sustained activity.

  • 29.
    Löfhed, Johan
    et al.
    University of Borås.
    Seoane, Fernando
    Thordstein, Magnus
    Salhgrenska University Hospital.
    Soft textile electrodes for EEG monitoring2010Conference paper (Refereed)
    Abstract [en]

    There is a need for long term monitoring of the brain during intensive care. This is e.g. the case for newborn babies that have been exposed to hypoxia during delivery. Electroencephalography (EEG) is the technique of choice. To get a clear and detailed view of the brain activity a large number of EEG electrodes should be used. Applying traditional electrodes one by one is a time-consuming and technically demanding work and therefore electrode caps are sometimes used. The existing caps have however been found to be suboptimal for long term monitoring because they may induce too high a pressure on the scalp of the babies. We have tested three different types of textile electrodes with regard to their potential use for EEG monitoring. The results show that soft conducting textile materials can indeed be used for EEG monitoring.

  • 30.
    Meli, Cristina
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Lansner, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    A modular attractor associative memory with patchy connectivity and weight pruning2013In: Network, ISSN 0954-898X, E-ISSN 1361-6536, Vol. 24, no 4, p. 129-150Article in journal (Refereed)
    Abstract [en]

    An important research topic in neuroscience is the study of mechanisms underlying memory and the estimation of the information capacity of the biological system. In this report we investigate the performance of a modular attractor network with recurrent connections similar to the cortical long-range connections extending in the horizontal direction. We considered a single learning rule, the BCPNN, which implements a kind of Hebbian learning and we trained the network with sparse random patterns. The storage capacity was measured experimentally for networks of size between 500 and 46 K units with a constant activity level, gradually diluting the connectivity. We show that the storage capacity of the modular network with patchy connectivity is comparable with the theoretical values estimated for simple associative memories and furthermore we introduce a new technique to prune the connectivity, which enhances the storage capacity up to the asymptotic value.

  • 31. Musunuri, Sravani
    et al.
    Khoonsari, Payam Emami
    Mikus, Maria
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wetterhall, Magnus
    Häggmark-Mänberg, Anna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lannfelt, Lars
    Erlandsson, Anna
    Bergquist, Jonas
    Ingelsson, Martin
    Shevchenko, Ganna
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Increased Levels of Extracellular Microvesicle Markers and Decreased Levels of Endocytic/Exocytic Proteins in the Alzheimer's Disease Brain2016In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 54, no 4, p. 1671-1686Article in journal (Refereed)
    Abstract [en]

    Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder accounting for more than 50% of all dementia cases. AD neuropathology is characterized by the formation of extracellular plaques and intracellular neurofibrillary tangles consisting of aggregated amyloid-beta and tau, respectively. The disease mechanism has only been partially elucidated and is believed to also involve many other proteins. Objective: This study intended to perform a proteomic profiling of post mortem AD brains and compare it with control brains as well as brains from other neurological diseases to gain insight into the disease pathology. Methods: Here we used label-free shotgun mass spectrometry to analyze temporal neocortex samples from AD, other neurological disorders, and non-demented controls, in order to identify additional proteins that are altered in AD. The mass spectrometry results were verified by antibody suspension bead arrays. Results: We found 50 proteins with altered levels between AD and control brains. The majority of these proteins were found at lower levels in AD. Pathway analyses revealed that several of the decreased proteins play a role in exocytic and endocytic pathways, whereas several of the increased proteins are related to extracellular vesicles. Using antibody-based analysis, we verified the mass spectrometry results for five representative proteins from this group of proteins (CD9, HSP72, PI42A, TALDO, and VAMP2) and GFAP, a marker for neuroinflammation. Conclusions: Several proteins involved in exo-endocytic pathways and extracellular vesicle functions display altered levels in the AD brain. We hypothesize that such changes may result in disturbed cellular clearance and a perturbed cell-to-cell communication that may contribute to neuronal dysfunction and cell death in AD.

  • 32.
    Nordberg, Axel
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    Treatment of Bone Fractures Using Fibre Reinforced Adhesive Patches2009Doctoral thesis, comprehensive summary (Other academic)
  • 33. Patton, D. A.
    et al.
    McIntosh, A. S.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    The biomechanical determinants of concussion: Kinematic and tissue-level predictors of injury2012In: ASME 2012 Summer Bioengineering Conference, SBC 2012, ASME Press, 2012, p. 507-508Conference paper (Refereed)
  • 34. Pedersen, Kyrre
    et al.
    Fahlstedt, Madelen
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Jacobsson, Anders
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    von Holst, Hans
    KTH, School of Technology and Health (STH), Ergonomics (Closed 20130701).
    A National Survey of Traumatic Brain Injuries Admitted to Hospitals in Sweden from 1987 to 20102015In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 45, no 1, p. 20-27Article in journal (Refereed)
    Abstract [en]

    Background: With an increasing and aging population, there is a global demand for improving the primary prevention strategies aimed at reducing traumatic brain injuries (TBIs). The objective of the present epidemiological study was to evaluate the pattern of TBI in Sweden over a 24 years period (1987-2010). Methods: The Swedish Hospital Discharge Register was used, where in-patient care with a main diagnosis of TBI according to ICD9/10 was included. External factors, age and gender distribution was evaluated. Results: A decreasing number of annual incidence was observed, that is, from 230 to 156 per 100,000 inhabitants. A steady decrease of concussion was observed while other intracranial injuries increased especially traumatic subdural hemorrhage and subarachnoid hemorrhage. The study identified 3 groups of patients young, adults and elderly. The highest incidence and the largest increase of incidence were seen in the oldest age group (85+ years) while the population under 65 years had a decreasing incidence of TBI. The most frequent etiology was fall accidents (57%) with a relative constant trend over the study period. Conclusions: More effort should be focused on different strategies for different age groups, especially the elderly group. A well-planned strategy for primary prevention guidelines for different age groups will have the chance to further reduce not only the health-care costs but also complications among elderly care. (C) 2015 S. Karger AG, Basel

  • 35.
    Ramanujam, Ryan
    et al.
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.). Karolinska Institutet, Sweden.
    Hedström, A. -K
    Manouchehrinia, A.
    Alfredsson, L.
    Olsson, T.
    Bottai, M.
    Hillert, J.
    Effect of smoking cessation on multiple sclerosis prognosis2015In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 72, no 10, p. 1117-1123Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is detrimental. OBJECTIVE: To determine whether smoking after MS diagnosis is associated with a change in time to SP disease. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients with prevalent MS who smoked at diagnosis (n = 728) taken from the Genes and Environment in Multiple Sclerosis Study, which consists of patients from the Swedish National MS Registry. The study entrance date was at time of first-year smoking. The study was conducted between November 2008 and December 2011, with patient environmental data collected from November 2009 to March 2011 via questionnaire. Study participants were from all counties in Sweden diagnosed as havingMS at the time of the Genes and Environment in Multiple Sclerosis Study and registered in the Swedish National MS Registry. Patients with MS with relapsing-remitting disease course or SP were included. These patients' conditions were diagnosed according to the McDonald criteria and the patients responded to recruitment letters with detailed questionnaires. EXPOSURE: Smoking, considered yearly after diagnosis and combined into a time-invariant covariate before diagnosis. MAINOUTCOMES ANDMEASURES: Time to SPMS, measured using an accelerated failure time model, with smoking as a time-varying covariate. Other covariates included sex, age at diagnosis, snuff use, and smoking before diagnosis. RESULTS: The optimized model illustrated that each additional year of smoking after diagnosis accelerated the time to conversion to SPMS by 4.7% (acceleration factor, 1.047; 95% CI, 1.023-1.072; P <.001). Kaplan-Meier plots demonstrated that those who continued to smoke continuously each year after diagnosis converted to SPMS faster than those who quit smoking, reaching SP disease at 48 and 56 years of age, respectively. CONCLUSIONS AND RELEVANCE: This study provides evidence that continued smoking is associated with an acceleration in time to SPMS and that those who quit fare better. Therefore, wepropose that patients withMS should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating MS-related disability.

  • 36. Ruiz-Riquelme, A.
    et al.
    Sánchez-Iglesias, S.
    Rábano, A.
    Guillén-Navarro, E.
    Domingo-Jiménez, R.
    Ramos, A.
    Rosa, I.
    Senra, A.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    García, Á.
    Araújo-Vilar, D.
    University of Santiago de Compostela-IDIS, Spain.
    Requena, J. R.
    University of Santiago de Compostela-IDIS, Spain.
    Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease2015In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 83, p. 44-53, article id 3572Article in journal (Refereed)
    Abstract [en]

    Celia's Encephalopathy (MIM #. 615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6-8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers.

  • 37.
    Salvadego, Desy
    et al.
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy..
    Keramidas, Michail E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Kölegård, Roger
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Brocca, Lorenza
    Univ Pavia, Dept Mol Med, Pavia, Italy..
    Lazzer, Stefano
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy..
    Mavelli, Irene
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy..
    Rittweger, Joern
    German Aerosp Ctr, Inst Aerosp Med, Cologne, Germany.;Univ Cologne, Fac Med, Dept Pediat & Adolescent Med, Cologne, Germany..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, Igor B.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot, Ljubljana, Slovenia.;Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada..
    Grassi, Bruno
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy.;CNR, Inst Bioimaging & Mol Physiol, Milan, Italy..
    PlanHab(*): hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone2018In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 596, no 15, p. 3341-3355Article in journal (Refereed)
    Abstract [en]

    Skeletal muscle oxidative function was evaluated in 11 healthy males (mean +/- SD age 27 +/- 5years) prior to (baseline data collection, BDC) and following a 21day horizontal bed rest (BR), carried out in normoxia (P-IO2=133 mmHg; N-BR) and hypoxia (P-IO2=90 mmHg; H-BR). H-BR was aimed at simulating reduced gravity habitats. The effects of a 21day hypoxic ambulatory confinement (P-IO2=90 mmHg; H-AMB) were also assessed. Pulmonary O-2 uptake (<(V) over dot>O-2), vastus lateralis fractional O-2 extraction (changes in deoxygenated haemoglobin+myoglobin concentration, Delta[deoxy(Hb+Mb)]; near-infrared spectroscopy) and femoral artery blood flow (ultrasound Doppler) were evaluated during incremental one-leg knee-extension exercise (reduced constraints to cardiovascular O-2 delivery) carried out to voluntary exhaustion in a normoxic environment. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibres. <(V) over dot>(O2peak) decreased (P<0.05) after N-BR (0.98 +/- 0.13 L min(-1)) and H-BR (0.96 +/- 0.17 L min(-1)) vs. BDC (1.05 +/- 0.14 L min(-1)). In the presence of a decreased (by similar to 6-8%) thigh muscle volume, <(V) over dot>(O2peak) normalized per unit of muscle mass was not affected by both interventions. Delta[deoxy(Hb+Mb)](peak) decreased (P<0.05) after N-BR (65 +/- 13% of limb ischaemia) and H-BR (62 +/- 12%) vs. BDC (73 +/- 13%). H-AMB did not alter <(V) over dot>(O2peak) or Delta[deoxy(Hb+Mb)](peak). An overshoot of Delta[deoxy(Hb+Mb)] was evident during the first minute of unloaded exercise after N-BR and H-BR. Arterial blood flow to the lower limb during both unloaded and peak knee extension was not affected by any intervention. Maximal ADP-stimulated mitochondrial respiration decreased (P<0.05) after all interventions vs. control. In 21day N-BR, a significant impairment of oxidative metabolism occurred downstream of cardiovascular O-2 delivery, affecting both mitochondrial respiration and presumably the intramuscular matching between O-2 supply and utilization. Superposition of H on BR did not worsen the impairment induced by BR alone.

  • 38.
    Schain, Martin
    et al.
    Karolinska Institutet.
    Benjaminsson, Simon
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Varnäs, Katarina
    Karolinska Institutet.
    Forsberg, Anton
    Karolinska Institutet.
    Halldin, Christer
    Karolinska Institutet.
    Lansner, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Farde, Lars
    Karolinska Institutet.
    Varrone, Andrea
    Arterial input function derived from pairwise correlations between PET-image voxels2013In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 33, no 7, p. 1058-1065Article in journal (Refereed)
    Abstract [en]

    A metabolite corrected arterial input function is a prerequisite for quantification of positron emission tomography (PET) data by compartmental analysis. This quantitative approach is also necessary for radioligands without suitable reference regions in brain. The measurement is laborious and requires cannulation of a peripheral artery, a procedure that can be associated with patient discomfort and potential adverse events. A non invasive procedure for obtaining the arterial input function is thus preferable. In this study, we present a novel method to obtain image-derived input functions (IDIFs). The method is based on calculation of the Pearson correlation coefficient between the time-activity curves of voxel pairs in the PET image to localize voxels displaying blood-like behavior. The method was evaluated using data obtained in human studies with the radioligands [11C]flumazenil and [11C]AZ10419369, and its performance was compared with three previously published methods. The distribution volumes (VT) obtained using IDIFs were compared with those obtained using traditional arterial measurements. Overall, the agreement in VT was good (~3% difference) for input functions obtained using the pairwise correlation approach. This approach performed similarly or even better than the other methods, and could be considered in applied clinical studies. Applications to other radioligands are needed for further verification.

  • 39.
    Sedzik, Jan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology.
    Jastrzebski, Jan Pawel
    Ikenaka, Kazuhiro
    Sequence motifs of myelin membrane proteins: Towards the molecular basis of diseases2013In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 91, no 4, p. 479-493Article in journal (Refereed)
    Abstract [en]

    The shortest sequence of amino acids in protein containing functional and structural information is a motif. To understand myelin protein functions, we intensively searched for motifs that can be found in myelin proteins. Some myelin proteins had several different motifs or repetition of the same motif. The most abundant motif found among myelin proteins was a myristoylation motif. Bovine MAG held 11 myristoylation motifs and human myelin basic protein held as many as eight such motifs. PMP22 had the fewest myristoylation motifs, which was only one; rat PMP22 contained no such motifs. Cholesterol recognition/interaction amino-acid consensus (CRAC) motif was not found in myelin basic protein. P2 protein of different species contained only one CRAC motif, except for P2 of horse, which had no such motifs. MAG, MOG, and P0 were very rich in CRAC, three to eight motifs per protein. The analysis of motifs in myelin proteins is expected to provide structural insight and refinement of predicted 3D models for which structures are as yet unknown. Analysis of motifs in mutant proteins associated with neurological diseases uncovered that some motifs disappeared in P0 with mutation found in neurological diseases. There are 2,500 motifs deposited in a databank, but 21 were found in myelin proteins, which is only 1% of the total known motifs. There was great variability in the number of motifs among proteins from different species. The appearance or disappearance of protein motifs after gaining point mutation in the protein related to neurological diseases was very interesting.

  • 40.
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS) (Closed 20130701).
    Electrical Bioimpedance Cerebral Monitoring: Fundamental Steps towards Clinical Application2007Doctoral thesis, comprehensive summary (Other academic)
  • 41.
    Seoane, Fernando
    et al.
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS) (Closed 20130701).
    Lindecrantz, Kaj
    Influence of the Skull and the Scalp on the Electrical Impedance of the Head and the Implications on Detection of Brain Cellular Edema2005In: IFMBE proceedings of the 12th International Conference on Biomedical Engineering, Singapore: Springer , 2005Conference paper (Refereed)
  • 42.
    Seoane, Fernando
    et al.
    University of Borås.
    Lindecrantz, Kaj
    University of Borås.
    The Transcephalic Electrical Impedance Method: Principles for Brain Tissue State Monitoring2005In: EU-Biopattern Brain Workshop / [ed] Emmanuel Ifeachor & Kaj Lindecrantz, 2005, p. 11-12Conference paper (Other academic)
  • 43. Seoane, Fernando
    et al.
    Lindecrantz, Kaj
    Olsson, T
    Kjellmer, I
    Flisberg, A
    Bagenholm, R
    Brain electrical impedance at various frequencies: the effect of hypoxia2004In: Proceedings of the 26th Annual International Conference of the IEEE EMBS, San Francisco, CA, USA • September 1-5, 2004, IEEE Engineering in Medicine and Biology Society , 2004, Vol. 3, p. 2322-2325Conference paper (Refereed)
    Abstract [en]

    Non-invasive multi-frequency measurements of transcephalic impedance, both reactance and resistance, can efficiently detect cell swelling of brain tissue and can be used for early detection of threatening brain damage. We have performed experiments on piglets to monitor transcephalic impedance during hypoxia. The obtained results have confirmed the hypothesis that changes in the size of cells modify the tissue impedance. During tissue inflammation after induced hypoxia, cerebral tissue exhibits changes in both reactance and resistance. Those changes are remarkably high, up to 71% over the baseline, and easy to measure especially at certain frequencies. A better understanding of the electrical behaviour of cerebral tissue during cell swelling would lead us to develop effective non-invasive clinical tools and methods for early diagnosis of cerebral edema and brain damage prevention.

  • 44. Seoane, Fernando
    et al.
    Lindecrantz, Kaj
    Olsson, Torsten
    Kjellmer, Ingemar
    Fliesberg, Anders
    Bågenholm, Ralph
    Electrical Bioimpedance Cerebral Monitoring2005In: Medicinteknikdagarna, 2005Conference paper (Other academic)
  • 45. Seoane, Fernando
    et al.
    Lindecrantz, Kaj
    Olsson, Torsten
    Kjellmer, Ingemar
    Flisberg, Anders
    Bågenholm, Ralph
    Spectroscopy study of the dynamics of the transencephalic electrical impedance in the perinatal brain during hypoxia2005In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 26, no 5, p. 849-863Article in journal (Refereed)
    Abstract [en]

    Hypoxia/ischaemia is the most common cause of brain damage in neonates. Thousands of newborn children suffer from perinatal asphyxia every year. The cells go through a response mechanism during hypoxia/ischaemia, to maintain the cellular viability and, as a response to the hypoxic/ischaemic insult, the composition and the structure of the cellular environment are altered. The alterations in the ionic concentration of the intra- and extracellular and the consequent cytotoxic oedema, cell swelling, modify the electrical properties of the constituted tissue. The changes produced can be easily measured using electrical impedance instrumentation. In this paper, we report the results from an impedance spectroscopy study on the effects of the hypoxia on the perinatal brain. The transencephalic impedance, both resistance and reactance, was measured in newborn piglets using the four-electrode method in the frequency range from 20 kHz to 750 kHz and the experimental results were compared with numerical results from a simulation of a suspension of cells during cell swelling. The experimental results make clear the frequency dependence of the bioelectrical impedance, confirm that the variation of resistance is more sensitive at low than at high frequencies and show that the reactance changes substantially during hypoxia. The resemblance between the experimental and numerical results proves the validity of modelling tissue as a suspension of cells and confirms the importance of the cellular oedema process in the alterations of the electrical properties of biological tissue. The study of the effects of hypoxia/ischaemia in the bioelectrical properties of tissue may lead to the development of useful clinical tools based on the application of bioelectrical impedance technology.

  • 46.
    Seoane, Fernando
    et al.
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS) (Closed 20130701).
    Lindecrantz, Kaj
    Olsson, Torsten
    Kjellmer, Ingemar
    Mallard, Carina
    Evolution of Cerebral Bioelectrical Resistance at Various Frequencies During Hypoxia in Fetal Sheep2004In: Australasian Physical & Engineering Sciences in Medicine, ISSN 0158-9938, Vol. 27, no 4Article in journal (Refereed)
  • 47.
    Seoane, Fernando
    et al.
    University College of Borås.
    Mai, Lu
    Persson, Mikael
    Lindecrantz, Kaj
    University College of Borås.
    The Role of the Cerebrospinal Fluid in the Distribution of Electrical Current within the Brain and its Implications for Electrical Bioimpedance Cerebral Monitoring2007In: Medicinteknikdagarna, 2007, Vol. 1Conference paper (Other academic)
  • 48.
    Skeppholm, Martin
    et al.
    Stockholm Spine Center, Löwenströmska Sjukhuset.
    Svedmark, Per
    Karolinska Institutet at Karolinska University Hospital Solna.
    Noz, Marilyn E.
    New York University.
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS, Radio Systems Laboratory (RS Lab).
    Olivecrona, Henrik
    Olerud, Claes
    Department of Orthopedic Surgery, Uppsala University Hospital.
    Evaluation of mobility and stability in the Discover artificial disc: an in vivo motion study using high-accuracy 3D CT data2015In: Journal of Eurosurgery : Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 23, no 3, p. 383-389Article in journal (Refereed)
    Abstract [en]

    OBJECT Artificial disc replacement (ADR) devices are unlike implants used in cervical fusion in that they are continuously exposed to stress not only within the implant site but also at their site of attachment to the adjacent vertebra. An imaging technique with higher accuracy than plain radiography and with the possibility of 3D visualization would provide more detailed information about the motion quality and stability of the implant in relation to the vertebrae. Such high-accuracy studies have previously been conducted with radiostereometric analysis (RSA), which requires implantation of tantalum markers in the adjacent vertebrae. The aim of this study was to evaluate in vivo motion and stability of implanted artificial discs. A noninvasive analysis was performed with CT, with an accuracy higher than that of plain radiographs and almost as high as RSA in cervical spine. METHODS Twenty-eight patients with ADR were included from a larger cohort of a randomized controlled trial comparing treatment of cervical radiculopathy with ADR or anterior cervical decompression and fusion. Surgical levels included C4-7; 18 patients had 1-level surgery and 10 patients had 2-level surgery. Follow-up time ranged from 19 to 50 months, with an average of 40 months. Two CT volumes of the cervical spine, 1 in flexion and 1 in extension, were obtained in each patient and then spatially registered using a customized imaging tool, previously used and validated for the cervical spine. Motion between the components in the artificial disc, as well as motion between the components and adjacent vertebrae, were calculated in 3 planes. Intraclass correlation (ICC) between independent observers and repeatability of the method were also calculated. RESULTS Intrinsic motion, expressed as degrees in rotation and millimeters in translation, was detectable in a majority of the ADRs. In the sagittal plane, in which the flexion/extension was performed, sagittal rotation ranged between 0.2 and 15.8 and translation between 0.0 and 5.5 mm. Eight percent of the ADRs were classified as unstable, as motion between at least 1 of the components and the adjacent vertebra was detected. Five percent were classified as ankylotic, with no detectable motion, and another 8% showed very limited motion due to heterotopic ossification. Repeatability for the motion in the sagittal plane was calculated to be 1.300 for rotation and 1.29 mm for translation (95% confidence level), ICC 0.99 and 0.84, respectively. All 3 patients with unstable devices had undergone 1-level ADRs at C5-6. They all underwent revision surgery due to increased neck pain, and instability was established during the surgery. CONCLUSIONS The majority of the artificial discs in this study showed intrinsic mobility several years after implantation and were also shown to be properly attached. Implant instability was detected in 8% of patients and, as all of these patients underwent revision surgery due to increasing neck pain, this might be a more serious problem than heterotopic bone formation.

  • 49. Spitali, P.
    et al.
    Tsonaka, R.
    Hettne, K.
    Koeks, Z.
    Roos, A.
    Straub, V.
    Domingos, J. Piscos
    Muntoni, F.
    Al-Khalili-Szigyarto, Cristina
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Lochmueller, H.
    Niks, E.
    Aartsma-Rus, A.
    Longitudinal proteomic analysis of sera allows to non-invasively monitor disease progression in Duchenne muscular dystrophy2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, p. S168-S168Article in journal (Other academic)
  • 50.
    Szigyarto, Cristina Al-Khalili
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Spitali, Pietro
    Leiden Univ, Med Ctr, Dept Human Genet, Albinusdreef 2, NL-2333 AA Leiden, Netherlands..
    Biomarkers of Duchenne muscular dystrophy: current findings2018In: Degenerative Neurological and Neuromuscular Disease, ISSN 1179-9900, Vol. 8, p. 1-13Article, review/survey (Refereed)
    Abstract [en]

    Numerous biomarkers have been unveiled in the rapidly evolving biomarker discovery field, with an aim to improve the clinical management of disorders. In rare diseases, such as Duchenne muscular dystrophy, this endeavor has created a wealth of knowledge that, if effectively exploited, will benefit affected individuals, with respect to health care, therapy, improved quality of life and increased life expectancy. The most promising findings and molecular biomarkers are inspected in this review, with an aim to provide an overview of currently known biomarkers and the technological developments used. Biomarkers as cells, genetic variations, miRNAs, proteins, lipids and/or metabolites indicative of disease severity, progression and treatment response have the potential to improve development and approval of therapies, clinical management of DMD and patients' life quality. We highlight the complexity of translating research results to clinical use, emphasizing the need for biomarkers, fit for purpose and describe the challenges associated with qualifying biomarkers for clinical applications.

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