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  • 1.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Outcome of microdialysis sampling on liver surface and parenchyma2016In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 200, no 2, p. 480-487Article in journal (Refereed)
    Abstract [en]

    Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.

    Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.

    Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.

    Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.

  • 2.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Detection of myocardial ischaemia using surface microdialysis on the beating heart2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 3, p. 175-181Article in journal (Refereed)
    Abstract [en]

    Microdialysis (MD) can be used to study metabolism of the beating heart. We investigated whether microdialysis results obtained from epicardial (surface) sampling reflect acute changes in the same way as myocardial sampling from within the substance of the ventricular wall. In anaesthetized open-thorax pigs a coronary snare was placed. One microdialysis probe was placed with the sampling membrane intramyocardially (myocardial), and a second probe was placed with the sampling membrane epicardially (surface), both in the area which was made ischaemic. Ten minutes collection intervals were used for microdialysis samples. Samples from 19 pigs were analysed for lactate, glucose, pyruvate and glycerol during equilibration, baseline, ischaemia and reperfusion periods. For both probes (surface and myocardial), a total of 475 paired simultaneous samples were analysed. Results from analyses showed no differences in relative changes for glucose, lactate and glycerol during baseline, ischaemia and reperfusion. Surface microdialysis sampling is a new application of the microdialysis technique that shows promise and should be further studied.

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  • 3.
    Ainegren, Mats
    et al.
    Sports Tech Research Centre, Department of Quality Management and Mechanical Engineering, Mid Sweden University, Östersund, Sweden.
    Hanstock, Helen
    Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Breathing resistance in heat and moisture exchanging devices2022In: Proceedings of the Institution of Mechanical Engineers, Part P: Journal of Sports Engineering and Technology, ISSN 1754-3371, Vol. 236, no 2, p. 97-105Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the resistance to breathing (RES) in heat and moisture exchanging devices (HME) intended for use during physical activity in the cold. RES was investigated for seventeen HMEs, including different types of filters. In addition, the influence of headwind on RES was tested using four representative HMEs. HMEs were mounted to the face of an artificial head manufactured from ABS plastic. The HMEs were connected to a mechanical lung simulator, which delivered standardised inspiratory and expiratory air flow rates (V⋅, L/s). The delta pressure (Δp, Pa) between ambient air and the air inside the HME was measured, whereupon RES was calculated. The results showed significant (p < 0.05) differences in RES between HMEs from different manufacturers, while the difference was smaller, and in some cases not significant (p > 0.05), between different models/filters within the same brand. The results also showed that RES was highly influenced by different ventilations and headwind conditions. RES increased with increased V⋅ and, when a headwind was introduced, RES decreased during inspiration and increased during expiration. Calculations showed that the oxygen and energy cost for breathing through an HME was very small for most of the tested models. The effect of HME dead space on pulmonary gas fractions depends on the tidal volume. At large tidal volumes and ventilations, the effect of HMEs on pulmonary gas fractions becomes relatively small.

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  • 4.
    Ali, Hazrat
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Umander, Johannes
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Rohlén, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    A Deep Learning Pipeline for Identification of Motor Units in Musculoskeletal Ultrasound2020In: IEEE Access, E-ISSN 2169-3536, Vol. 8, p. 170595-170608Article in journal (Refereed)
    Abstract [en]

    Skeletal muscles are functionally regulated by populations of so-called motor units (MUs). An MU comprises a bundle of muscle fibers controlled by a neuron from the spinal cord. Current methods to diagnose neuromuscular diseases and monitor rehabilitation, and study sports sciences rely on recording and analyzing the bio-electric activity of the MUs. However, these methods provide information from a limited part of a muscle. Ultrasound imaging provides information from a large part of the muscle. It has recently been shown that ultrafast ultrasound imaging can be used to record and analyze the mechanical response of individual MUs using blind source separation. In this work, we present an alternative method - a deep learning pipeline - to identify active MUs in ultrasound image sequences, including segmentation of their territories and signal estimation of their mechanical responses (twitch train). We train and evaluate the model using simulated data mimicking the complex activation pattern of tens of activated MUs with overlapping territories and partially synchronized activation patterns. Using a slow fusion approach (based on 3D CNNs), we transform the spatiotemporal image sequence data to 2D representations and apply a deep neural network architecture for segmentation. Next, we employ a second deep neural network architecture for signal estimation. The results show that the proposed pipeline can effectively identify individual MUs, estimate their territories, and estimate their twitch train signal at low contraction forces. The framework can retain spatio-temporal consistencies and information of the mechanical response of MU activity even when the ultrasound image sequences are transformed into a 2D representation for compatibility with more traditional computer vision and image processing techniques. The proposed pipeline is potentially useful to identify simultaneously active MUs in whole muscles in ultrasound image sequences of voluntary skeletal muscle contractions at low force levels.

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  • 5.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ekerot, Carl-Fredrik
    Department of Experimental Medical Sciences, Section for Neuroscience, Lund.
    The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.2013In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 591, no 22, p. 5453-5458Article in journal (Refereed)
    Abstract [en]

    The lateral reticular nucleus (LRN) is a major precerebellar centre of mossy fibre information to the cerebellum from the spinal cord that is distinct from the direct spinocerebellar paths. The LRN has traditionally been considered to provide the cerebellum with segregated information from several spinal systems controlling posture, reaching, grasping, locomotion, scratching and respiration. However, results are presented that show extensive convergence on a majority of LRN neurons from spinal systems. We propose a new hypothesis suggesting that the LRN may use extensive convergence from the different input systems to provide overview and integration of linked motor components to the cerebellum. This integrated information is sent in parallel with the segregated information from the individual systems to the cerebellum that finally may compare the activity and make necessary adjustments of various motor behaviours.

  • 6.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Isa, Tadashi
    Premotoneuronal and direct corticomotoneuronal control in the cat and macaque monkey.2002In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 508, p. 281-97Article in journal (Refereed)
    Abstract [en]

    The literature on premotoneuronal and direct corticomotoneuronal (CM) control in the cat and macaque monkey is reviewed. The available experimental findings are not in accordance with a recently proposed hypothesis that direct CM connections have "replaced" the premotoneuronal pathways. Instead, we propose that premotoneuronal CM control plays an important role in motor control also in primates and that the direct CM connection has been added during phylogeny.

  • 7.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pettersson, L G
    University of Gothenburg.
    Nishimura, Y
    National Institute for Physiological Sciences, Okazaki.
    Yoshino-Saito, K
    National Institute for Physiological Sciences, Okazaki.
    Tsuboi, F
    National Institute for Physiological Sciences, Okazaki.
    Takahashi, M
    National Institute for Physiological Sciences, Okazaki.
    Isa, T
    National Institute for Physiological Sciences, Okazaki.
    Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons2011In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 106, no 1, p. 122-126Article in journal (Refereed)
    Abstract [en]

    In motor control, the general view is still that spinal interneurons mainly contribute to reflexes and automatic movements. The question raised here is whether spinal interneurons can mediate the cortical command for independent finger movements, like a precision grip between the thumb and index finger in the macaque monkey, or if this function depends exclusively on a direct corticomotoneuronal pathway. This study is a followup of a previous report (Sasaki et al. J Neurophysiol 92: 3142-3147, 2004) in which we trained macaque monkeys to pick a small piece of sweet potato from a cylinder by a precision grip between the index finger and thumb. We have now isolated one spinal interneuronal system, the C3-C4 propriospinal interneurons with projection to hand and arm motoneurons. In the previous study, the lateral corticospinal tract (CST) was interrupted in C4/C5 (input intact to the C3-C4 propriospinal interneurons), and in this study, the CST was interrupted in C2 (input abolished). The precision grip could be performed within the first 15 days after a CST lesion in C4/C5 but not in C2. We conclude that C3-C4 propriospinal interneurons also can carry the command for precision grip.

  • 8.
    Andersson, Gustav
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Arteries in the area targeted with successful sclerosing injections for Achilles tendinosis are under distinct neural control2006Conference paper (Refereed)
    Abstract [en]

    It has been scientifically demonstrated that there are blood vessels with pathologically high blood flow inside and outside the ventral part of the Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. Injections of local anaesthesia on the outside of the ventral part of the tendon have been found to temporarily abolish the tendon pain, and this has been an inspiration in the development of a new approach in the treatment of tendinosis: Based on ultrasound- (US) and colour Doppler- (CD) guidance, the sclerosing substance polidocanol, for many years used in treatment of varicose veins, was injected targeting the area of high-flow blood vessels just outside the ventral part of the Achilles tendon. The treatment has in pilot studies and a randomized controlled clinical study been shown to cure the pain in about 70-80 % of the patients. Also, follow up examinations, using US and CD, have shown a possible remodeling potential of the tendon. There is some previous information available on the innervation patterns of the human Achilles tendon itself. However, the innervation patterns of the area just outside the ventral part of the tendon, i.e. the area that is targeted by the sclerosing injections (target area), are unknown. This includes a lack of information concerning the nerve-related characteristics of the blood vessels in the area. In this study, therefore, tissue specimens from this target area, obtained during surgical treatment of patients with chronic painful mid-portion Achilles tendinosis, were examined. Histological and immunohistochemical examinations were performed. In the tissue of the target area, in which loose connective tissue and fat cells were frequent constituents, there was a presence of arteries and nerve fascicles. The arteries were of varying dimensions, some being very large. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5 (PGP 9.5).  Some of the arteries were supplied by an extensive perivascular innervation, as seen via PGP 9.5 staining. As seen via processing for the rate limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), sympathetic innervation was found to be a constituent of this innervation. There was furthermore a marked occurrence of immunoreactions for the α1-adrenoreceptor in arterial walls. Also, there was a presence of immunoreactions for the substance P (SP)-preferred receptor, the neurokinin-1 (NK-1) receptor in arterial walls. This receptor was particularly detected in the endothelial parts. The study shows that the arteries in the target area are accompanied by nerve fascicles and that there is a presence of a perivascular innervation, as well as a presence of adrenergic and NK-1 receptors in arterial walls, in this region. Thus, arteries in this area are under distinct neural control. The nerve-related characteristics of the area targeted in the successful polidicanol injection treatment for Achilles tendinosis are here for the first time shown.

  • 9.
    Armstrong, Irene T
    et al.
    Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
    Judson, Melissa
    Department of Psychology, Queen's University, Kingston, ON, Canada.
    Munoz, Douglas P
    Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada, Department of Psychology, Queen's University, Kingston, ON, Canada, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J Randall
    Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada, Department of Psychology, Queen's University, Kingston, ON, Canada, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
    Waiting for a hand: saccadic reaction time increases in proportion to hand reaction time when reaching under a visuomotor reversal2013In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 7, p. 319-Article in journal (Refereed)
    Abstract [en]

    Although eye movement onset typically precedes hand movement onset when reaching to targets presented in peripheral vision, arm motor commands appear to be issued at around the same time, and possibly in advance, of eye motor commands. A fundamental question, therefore, is whether eye movement initiation is linked or yoked to hand movement. We addressed this issue by having participants reach to targets after adapting to a visuomotor reversal (or 180° rotation) between the position of the unseen hand and the position of a cursor controlled by the hand. We asked whether this reversal, which we expected to increase hand reaction time (HRT), would also increase saccadic reaction time (SRT). As predicted, when moving the cursor to targets under the reversal, HRT increased in all participants. SRT also increased in all but one participant, even though the task for the eyes-shifting gaze to the target-was unaltered by the reversal of hand position feedback. Moreover, the effects of the reversal on SRT and HRT were positively correlated across participants; those who exhibited the greatest increases in HRT also showed the greatest increases in SRT. These results indicate that the mechanisms underlying the initiation of eye and hand movements are linked. In particular, the results suggest that the initiation of an eye movement to a manual target depends, at least in part, on the specification of hand movement.

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  • 10.
    A'Roch, Roman
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gustafsson, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Poelaert, Jan
    Anesthesiology, University of Brussels, Belgium.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Left ventricular strain and peak systolic velocity: responses to controlled changes in load and contractility, explored in a porcine model2012In: Cardiovascular Ultrasound, E-ISSN 1476-7120, Vol. 10, no 1, article id 22Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tissue velocity echocardiography is increasingly used to evaluate global and regional cardiac function. Previous studies have suggested that the quantitative measurements obtained during ejection are reliable indices of contractility, though their load-sensitivity has been studied in different settings, but still remains a matter of controversy. We sought to characterize the effects of acute load change (both preload and afterload) and change in inotropic state on peak systolic velocity and strain as a measure of LV contractility.

    METHODS: Thirteen anesthetized juvenile pigs were studied, using direct measurement of left ventricular pressure and volume and transthoracic echocardiography. Transient inflation of a vena cava balloon catheter produced controlled load alterations. At least eight consecutive beats in the sequence were analyzed with tissue velocity echocardiography during the load alteration and analyzed for change in peak systolic velocities and strain during same contractile status with a controlled load alteration. Two pharmacological inotropic interventions were also included to generate several myocardial contractile conditions in each animal.

    RESULTS: Peak systolic velocities reflected the drug-induced changes in contractility in both radial and longitudinal axis. During the acute load change, the peak systolic velocities remain stable when derived from signal in the longitudinal axis and from the radial axis. The peak systolic velocity parameter demonstrated no strong relation to either load or inotropic intervention, that is, it remained unchanged when load was systematically and progressively varied (peak systolic velocity, longitudinal axis, control group beat 1- 5.72 +/- 1.36 with beat 8- 6.49 +/- 1.28 cm/sec, 95% confidence interval), with the single exception of the negative inotropic intervention group where peak systolic velocity decreased a small amount during load reduction (beat 1- 3.98 +/- 0.92 with beat 8- 2.72 +/- 0.89 cm/sec). Systolic strain, however, showed a clear degree of load-dependence.

    CONCLUSIONS: Peak systolic velocity appears to be load-independent as tested by beat-to-beat load reduction, while peak systolic strain appears to be load-dependent in this model. Peak systolic velocity, in a controlled experimental model where successive beats during load alteration are assessed, has a strong relation to contractility. Peak systolic velocity, but not peak strain rate, is largely independent of load, in this model. More study is needed to confirm this finding in the clinical setting.

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  • 11.
    A'Roch, Roman
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gustafsson, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Poelaert, Jan
    Anesthesiology, University of Brussels, Belgium.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Left ventricular twist is load-dependent as shown in a large animal model with controlled cardiac load2012In: Cardiovascular Ultrasound, E-ISSN 1476-7120, Vol. 10, article id 26Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Left ventricular rotation and twist can be assessed noninvasively by speckle tracking echocardiography. We sought to characterize the effects of acute load change and change in inotropic state on rotation parameters as a measure of left ventricular (LV) contractility.

    METHODS: Seven anesthetised juvenile pigs were studied, using direct measurement of left ventricular pressure and volume and simultaneous transthoracic echocardiography. Transient inflation of an inferior vena cava balloon (IVCB) catheter produced controlled load reduction. First and last beats in the sequence of eight were analysed with speckle tracking (STE) during the load alteration and analysed for change in rotation/twist during controlled load alteration at same contractile status. Two pharmacological inotropic interventions were also included to examine the same hypothesis in additionally conditions of increased and decreased myocardial contractility in each animal. Paired comparisons were made for different load states using the Wilcoxon's Signed Rank test.

    RESULTS: The inferior vena cava balloon occlusion (IVCBO) load change compared for first to last beat resulted in LV twist increase (11.67degrees +/-2.65degrees vs. 16.17degrees +/-3.56degrees respectively, p < 0.004) during the load alteration and under adrenaline stimulation LV twist increase 12.56degrees +/-5.1degrees vs. 16.57degrees +/-4.6degrees (p < 0.013), and though increased, didn't reach significance in negative inotropic condition. Untwisting rate increased significantly at baseline from 41.7degrees/s +/-41.6degrees/s vs.122.6degrees/s +/-55.8degrees/s (P < 0.039) and under adrenaline stimulation untwisting rate increased (55.3degrees/s +/-3.8degrees/s vs.111.4degrees/s +/-24.0degrees/s (p < 0.05), but did not systematically changed in negative inotropic condition.

    CONCLUSIONS: Peak systolic LV twist and peak early diastolic untwisting rate are load dependent. Differences in LV load should be included in the interpretation when serial measures of twist are compared.

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  • 12.
    Athanassiadis, Tuija
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology. Umeå University, Faculty of Medicine, Odontology.
    Neural circuits engaged in mastication and orofacial nociception2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A deeper understanding of both movement control and the effects of nociceptor inputs on our motor systems is critical for proper clinical diagnosis of musculo-skeletal dysfunctions and for development of novel rehabilitation schemes. In the jaw system, masticatory movements are produced by a central pattern generator (CPG) located in the brainstem. Considerable efforts have been made in deciphering this neuronal network. The present thesis contributes towards an increasingly detailed understanding of its essential elements, and presents a hypothesis of how deep somatic pain (i.e. muscle pain) may be evoked and interferes with the masticatory CPG circuitry.

    In Paper I, the expression of c-Fos-like protein was used as a molecular marker to visualize brainstem neurons that were active during induced fictive mastication in the anesthetized and paralyzed rabbit. Our findings provide a previously lacking detailed record of the neuronal populations that form the masticatory motor pattern. Certain cells were located in brainstem areas previously suggested to be involved in the masticatory CPG. However, it was a new finding that neurons in the dorsal part of the trigeminal main sensory nucleus (NVsnpr-d) may belong to this circuitry. Paper II focused on the discovered neurons in NVsnpr in an in vitro slice preparation from young rats.  Intracellular recordings allowed us to define two cell types based on their response to depolarizing current. Microstimulation applied to the trigeminal motor nucleus, its reticular border, the parvocellular reticular formation and the nucleus reticularis pontis caudalis, elicited postsynaptic potentials in 81% of the neurons tested. Responses obtained were predominately excitatory and sensitive to gluta-matergic antagonists DNQX or/and APV. Some inhibitory and biphasic responses were also evoked. Bicuculline methiodide or strychnine blocked the IPSPs indicating that they were mediated by GABAA or glycinergic receptors. About one third of the stimulations activated both types of neurons antidromically. Neurons in NVsnpr-d seem to gather all the conditions that can theoretically account for a role in masticatory rhythm generation.

    In Paper III, the masticatory model system was used to investigate the possible role of muscle spindle primary afferents in development of persistent musculoskeletal pain. Following intramuscular acidic (pH 4.0) saline injections of rat masseter muscles, in vitro whole cell recordings were done from jaw closing muscle spindle somata located in the trigeminal mesencephalic nucleus (NVmes). Compared to control neurons, the somata of afferents exposed to acid had more hyperpolarized membrane potentials, more hyperpolarized thresholds for firing, high frequency membrane oscillations and ectopic bursting of action potentials. These changes in membrane properties lasted for up to 35 days. Within the same time frame experi-mental animals showed hypersensitivity to touch on the skin covering the injected muscle. Similar saline injections also resulted in a significant increase of activity dependent c-Fos expression in NVmes neurons compared to controls. Immuno-fluorescence and lectin binding studies indicated that small-caliber muscle afferents containing known nociceptor markers (CGRP, SP, P2X3, TRPV1 and IB4) and expressing glutamate receptors are found close to the annulo-spiral endings of the NVmes afferents. Combined, our new observations support the hypothesis that excessive release of glutamate, within muscle spindles due to ectopically evoked antidromic action potentials, could lead to development of persistent musculoskeletal pain by activation and/ or sensitization of adjacent muscle afferent nociceptors.

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  • 13.
    Awad, Amar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ryggmärgsskador av ”discomplete” -typ och smärta2015In: BestPractice Nordic, Vol. 6, no 12, p. 6-9Article in journal (Other academic)
  • 14.
    Awad, Amar
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor2020In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 209, article id 116511Article in journal (Refereed)
    Abstract [en]

    Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off.

    We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p ​≤ ​0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS ​× ​task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p ​≤ ​0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p ​≤ ​0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment.

    Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

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  • 15.
    Awad, Amar
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Levi, Richard
    Department of Rehabilitation Medicine in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University.
    Waller, Mikael
    Rehabilitation Medicine Clinic, Sunderby Hospital, Region Norrbotten.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Lindgren, Lenita
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Nursing.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI2020In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 131, no 5, p. 1059-1067Article in journal (Refereed)
    Abstract [en]

    Objective: Spinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI.

    Methods: We used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation).

    Results: Somatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants.

    Conclusions: Our results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI.

    Significance: Identifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity.

  • 16.
    Bagge, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon2009In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 24, no 7, p. 839-848Article in journal (Refereed)
    Abstract [en]

    Neurotrophins are substances that have been shown to be important in growth and remodelling phases in different types of tissue. There is no information concerning the possible occurrences of neurotrophins and their receptors in tendons. In this study, sections of both chronic painful (tendinosis) and pain-free (non-tendinosis) human Achilles tendons were immunohistochemically stained with antibodies against the neurotrophins NGF and BDNF, and their receptors TrkA, TrkB and p75. There were marked immunoreactions for NGF and BDNF in the tendon cells (tenocytes) of both tendinosis and non-tendinosis specimens. The tenocytes were also reactive for the receptor p75, but not for the receptors TrkA and TrkB. In addition, p75 immunoreactions were seen in nerve fascicles and in the walls of arterioles. This is the first study to identify neurotrophins in the tenocytes of human tendon. It is clear from this study that the local cells of tendons are sources of neurotrophins. The neurotrophins may play an important role in the tendon through their interaction with the receptor p75 in the tenocytes. These interactions may regulate tropic modulatory, and apoptotic effects. In conclusion, the observations show a new concept concerning production and function of neurotrophins, namely in the tenocytes of tendons.

  • 17.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology, University Clinical Centre of Kosova; Medical Faculty, University of Prishtina, Prishtina, Kosovo.
    Bytyci, Ibadete
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology, University Clinical Centre of Kosova.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Molecular & Clinical Sciences Research Institute, St George University, and Brunel University, London, UK.
    Left atrial structure and function predictors of recurrent fibrillation after catheter ablation: a systematic review and meta-analysis2020In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 40, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Background: Catheter ablation (CA) has become a conventional treatment for atrial fibrillation (AF), but remains with high recurrence rate. The aim of this meta-analysis was to determine left atrial (LA) structure and function indices that predict recurrence of AF.

    Methods: We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry, up to September 2017 in order to select clinical trials and observational studies which reported echocardiographic predictors of AF recurrence after CA. Eighty-five articles with a total of 16 126 patients were finally included.

    Results: The pooled analysis showed that after a follow-up period of 21 +/- 12 months, patients with AF recurrence had larger LA diameter with weighted mean difference (WMD: 2 center dot 99 ([95% CI 2 center dot 50-3 center dot 47], P<0 center dot 001), larger LA volume index (LAVI) maximal and LAVI minimal (P<0 center dot 0001 for both), larger LA area (P<0 center dot 0001), lower LA strain (P<0 center dot 0001) and lower LA total emptying fraction (LA EF) (P<0 center dot 0001) compared with those without AF recurrence. The most powerful LA predictors (in accuracy order) of AF recurrence were as follows: LA strain <19% (OR: 3 center dot 1[95% CI, -1.3-10 center dot 4], P<0 center dot 0001), followed by LA diameter >= 50 mm (OR: 2 center dot 75, [95% CI 1 center dot 66-4 center dot 56,] P<0 center dot 0001), and LAVmax >150 ml (OR: 2 center dot 25, [95% CI, 1.1-5 center dot 6], P = 0 center dot 0002).

    Conclusions: Based on this meta-analysis results, a dilated left atrium with diameter more than 50 mm and volume above 150 ml or myocardial strain below 19% reflect an unstable LA that is unlikely to hold sinus rhythm after catheter ablation for atrial fibrillation.

  • 18.
    Baugh, Lee A.
    et al.
    Queen's University Kingston, Ontario.
    Kao, Michelle
    Queen's University Kingston, Ontario.
    Johansson, Roland S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J. Randall
    Queen's University Kingston, Ontario.
    Material evidence: interaction of well-learned priors and sensorimotor memory when lifting objects2012In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 108, no 5, p. 1262-1269Article in journal (Refereed)
    Abstract [en]

    Skilled object lifting requires the prediction of object weight. When lifting new objects, such prediction is based on well-learned size-weight and material-density correlations, or priors. However, if the prediction is erroneous, people quickly learn the weight of the particular object and can use this knowledge, referred to as sensorimotor memory, when lifting the object again. In the present study, we explored how sensorimotor memory, gained when lifting a given object, interacts with well-learned material-density priors when predicting the weight of a larger but otherwise similar-looking object. Different groups of participants 1st lifted 1 of 4 small objects 10 times. These included a pair of wood-filled objects and a pair of brass-filled objects where 1 of each pair was covered in a wood veneer and the other was covered in a brass veneer. All groups then lifted a larger, brass-filled object with the same covering as the small object they had lifted. For each lift, we determined the initial peak rate of change of vertical load-force rate and the load-phase duration, which provide estimates of predicted object weight. Analysis of the 10th lift of the small cube revealed no effects of surface material, indicating participants learned the appropriate forces required to lift the small cube regardless of object appearance. However, both surface material and core material of the small cube affected the 1st lift of the large block. We conclude that sensorimotor memory related to object density can contribute to weight prediction when lifting novel objects but also that long-term priors related to material properties can influence the prediction.

  • 19.
    Bengs, Carita
    et al.
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Wiklund, Maria
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Kropp och hälsa2015In: Feministiskt tänkande och sociologi: teorier, begrepp och tillämpningar / [ed] Anna Hedenus, Sofia Björk, Oksana Shmulyar Gréen, Lund: Studentlitteratur AB, 2015, p. 151-167Chapter in book (Refereed)
  • 20. Bengtsson, Fredrik
    et al.
    Brasselet, Romain
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Arleo, Angelo
    Jörntell, Henrik
    Integration of sensory quanta in cuneate nucleus neurons in vivo2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 2, p. e56630-Article in journal (Refereed)
    Abstract [en]

    Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes) in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.

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  • 21.
    Bengtsson, Sara K. S.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Sjöstedt, Jessica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Das, Roshni
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umecrine Cognition AB, Solna, Sweden.
    Doverskog, Magnus
    Umecrine Cognition AB, Solna, Sweden.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umecrine Cognition AB, Solna, Sweden.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Department of Nursing Sciences, Mid Sweden University, Sundsvall, Sweden.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umecrine Cognition AB, Solna, Sweden.
    Extra-synaptic GABAA receptor potentiation and neurosteroid-induced learning deficits are inhibited by GR3027, a GABAA modulating steroid antagonist2023In: Biomolecules, E-ISSN 2218-273X, Vol. 13, no 10, article id 1496Article in journal (Refereed)
    Abstract [en]

    Objectives In Vitro: To study the effects of GR3027 (golexanolone) on neurosteroid-induced GABA-mediated current responses under physiological GABAergic conditions with recombinant human α5β3γ2L and α1β2γ2L GABAA receptors expressed in human embryonic kidney cells, using the response patch clamp technique combined with the Dynaflow™ application system. With α5β3γ2L receptors, 0.01–3 μM GR3027, in a concentration-dependent manner, reduced the current response induced by 200 nM THDOC + 0.3 µM GABA, as well as the THDOC-induced direct gated effect. GR3027 (1 μM) alone had no effect on the GABA-mediated current response or current in the absence of GABA. With α1β2γ2L receptors, GR3027 alone had no effect on the GABA-mediated current response or did not affect the receptor by itself. Meanwhile, 1–3 µM GR3027 reduced the current response induced by 200 nM THDOC + 30 µM GABA and 3 µM GR3027 that induced by 200 nM THDOC when GABA was not present. Objectives In Vivo: GR3027 reduces allopregnanolone (AP)-induced decreased learning and anesthesia in male Wistar rats. Rats treated i.v. with AP (2.2 mg/kg) or vehicle were given GR3027 in ratios of 1:0.5 to 1:5 dissolved in 10% 2-hydroxypropyl-beta-cyclodextrin. A dose ratio of AP:GR3027 of at least 1:2.5 antagonized the AP-induced decreased learning in the Morris Water Mase (MWM) and 1:7.5 antagonized the loss of righting reflex (LoR). GR3027 treatment did not change other functions in the rat compared to the vehicle group. Conclusions: GR3027 functions in vitro as an inhibitor of GABAA receptors holding α5β3γ2L and α1β2γ2L, in vivo, in the rat, as a dose-dependent inhibitor toward AP’s negative effects on LoR and learning in the MWM.

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  • 22.
    Bengtsson, Victor
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fysiologiska krav för fotbollsspelare på elitnivå och implementering av träning2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Soccer is one of the most popular sports in the world and is played all over the world. Soccer is dependent upon many different skills such as player intelligens, technique, psychological factors and physique. During the last decades the physiological demands of elite soccer players has increased. Thus an appropriate endurance and strength training is of importance to optimise the performance. Therefore the purpose of this review is to analyze the physiological demands of soccer players and to provide science-based recommendations on how to improve these with physical training. During a soccer game the players run about 10-12 km in an intermittent movement pattern. The avarage intensity corresponds to 70-90% of VO2-max and 90% of the energy production is of aerobic character. Furthermore soccer players perform about 1200 activity changes during a soccer game by which 150-250 is intensive actions relying on anaerobic energy production. The VO2-max and repeated sprint ability has been shown to be important factors that correlates to the players activity profiles during a soccer game. High-intensity intervall training has been proved to be succesful to ameliorate the endurance and soccer performance. Recent studies has also shown small sided games and soccer specific exercise drills to be effective in improving VO2-max and the repeated sprint ability. In addition to the endurance training, the physical training should also consist of strength training to improve the sprint performance

  • 23.
    Bergström, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    The conjunction of non-consciously perceived object identity and spatial position can be retained during a visual short-term memory task2015In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 6, article id 1470Article in journal (Refereed)
    Abstract [en]

    Although non-consciously perceived information has previously been assumed to be short-lived (<500 ms), recent findings show that non-consciously perceived information can be maintained for at least 15s Such findings can be explained as working memory without a conscious experience of the information to be retained. However, whether or not working memory can operate on non-consciously perceived information remains controversial, and little is known about the nature of such non-conscious visual short-term memory (VSTM). Here we used continuous flash suppression to render stimuli non-conscious, to investigate the properties of non-consciously perceived representations in delayed match-to-sample (DMS) tasks. In Experiment I we used variable delays (5 or 15s) and found that performance was significantly better than chance and was unaffected by delay duration, thereby replicating previous findings. In Experiment II the DMS task required participants to combine information of spatial position and object identity on a trial-by-trial basis to successfully solve the task. We found that the conjunction of spatial position and object identity was retained, thereby verifying that non-conscious, trial-specific information can be maintained for prospective use. We conclude that our results are consistent with a working memory interpretation, but that more research is needed to verify this interpretation.

  • 24.
    Birznieks, Ingvars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Tactile Sensory Control of Dexterous Manipulation in Humans2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    During dexterous manipulation with the fingertips, forces are applied to objects' surfaces. To achieve grasp stability, these forces must be appropriate given the properties of the objects and the skin of the fingertips, and the nature of the task. It

    has been demonstrated that tactile sensors in the fingertips provide crucial information about both object properties and mechanical events critical for the control of fingertip forces, while in certain tasks vision may also contribute to predictions of required fingertip actions. This thesis focuses on two specific aspects of the sensory control of manipulation: (i) how individual fingers are controlled for grasp stability when people restrain objects subjected to unpredictable forces tangential to the grasped surfaces, and (ii) how tactile sensors in the fingertips encode direction of fingertip forces and shape of surfaces contacted by the fingertips.

    When restraining objects with two fingers, subjects adjust the fingertip forces to the local friction at each digit-object interface for grasp stability. This is accomplished primarily by partitioning the tangential force between the digits in a way that reflects the local friction whereas the normal forces at the involved digits are scaled by the average friction and the total load. The neural control mechanisms in this task rely on tactile information pertaining to both the friction at each digit-object interface and the development of tangential load. Moreover, these mechanisms controlled the force application at individual digits while at the same time integrating sensory inputs from all digits involved in the task.

    Microneurographical recordings in awake humans shows that most SA-I, SA-II and FA-I sensors in the distal phalanx are excited when forces similar to those observed during actual manipulation are applied to the fingertip. Moreover, the direction of the fingertip force influences the impulse rates in most afferents and their responses are broadly tuned to a preferred direction. The preferred direction varies among the afferents and, accordingly, ensembles of afferents can encode the direction of fingertip forces. The local curvature of the object in contact with the fingertip also influenced the impulse rates in most afferents, providing a curvature contrast signals within the afferent populations. Marked interactions were observed in the afferents' responses to object curvature and force direction. Similar findings were obtained for the onset latency in individual afferents. Accordingly, for ensembles of afferents, the order by which individual afferents initially discharge to fingertip events effectively represents parameters of fingertip stimulation. This neural code probably represents the fastest possible code for transmission of parameters of fingertip stimuli to the CNS.

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  • 25.
    Birznieks, Ingvars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Jenmalm, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Goodwin, Antony W
    University of Melbourne, Victoria.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Encoding of direction of fingertip forces by human tactile afferents2001In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 21, no 20, p. 8222-8237Article in journal (Refereed)
    Abstract [en]

    In most manipulations, we use our fingertips to apply time-varying forces to the target object in controlled directions. Here we used microneurography to assess how single tactile afferents encode the direction of fingertip forces at magnitudes, rates, and directions comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to a standard site on the fingertip while recording impulse activity in 196 tactile afferents with receptive fields distributed over the entire terminal phalanx. Forces were applied in one of five directions: normal force and forces at a 20 degrees angle from the normal in the radial, distal, ulnar, or proximal directions. Nearly all afferents responded, and the responses in most slowly adapting (SA)-I, SA-II, and fast adapting (FA)-I afferents were broadly tuned to a preferred direction of force. Among afferents of each type, the preferred directions were distributed in all angular directions with reference to the stimulation site, but not uniformly. The SA-I population was biased for tangential force components in the distal direction, the SA-II population was biased in the proximal direction, and the FA-I population was biased in the proximal and radial directions. Anisotropic mechanical properties of the fingertip and the spatial relationship between the receptive field center of the afferent and the stimulus site appeared to influence the preferred direction in a manner dependent on afferent type. We conclude that tactile afferents from the whole terminal phalanx potentially contribute to the encoding of direction of fingertip forces similar to those that occur when subjects manipulate objects under natural conditions.

  • 26.
    Birznieks, Ingvars
    et al.
    Prince of Wales Medical Research Institute, Sydney, New South Wales 2031, Australia.
    Macefield, Vaughan G
    Prince of Wales Medical Research Institute, Sydney, New South Wales 2031, Australia.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces2009In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 29, no 29, p. 9370-9379Article in journal (Refereed)
    Abstract [en]

    There are clusters of slowly adapting (SA) mechanoreceptors in the skin folds bordering the nail. These "SA-IInail" afferents, which constitute nearly one fifth of the tactile afferents innervating the fingertip, possess the general discharge characteristics of slowly adapting type II (SA-II) tactile afferents located elsewhere in the glabrous skin of the human hand. Little is known about the signals in the SA-IInail afferents when the fingertips interact with objects. Here we show that SA-IInail afferents reliably respond to fingertip forces comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to the finger pad while recording impulse activity in 17 SA-IInail afferents. Ramp-and-hold forces (amplitude 4 N, rate 10 N/s) were applied normal to the skin, and at 10, 20, or 30 degrees from the normal in eight radial directions with reference to the primary site of contact (25 force directions in total). All afferents responded to the force stimuli, and the responsiveness of all but one afferents was broadly tuned to a preferred direction of force. The preferred directions among afferents were distributed all around the angular space, suggesting that the population of SA-IInail afferents could encode force direction. We conclude that signals in the population of SA-IInail afferents terminating in the nail walls contain vectorial information about fingertip forces. The particular tactile features of contacted surfaces would less influence force-related signals in SA-IInail afferents than force-related signals present in afferents terminating in the volar skin areas that directly contact objects.

  • 27. Bitaraf, Nazanin
    et al.
    Ahmed, Ahmed
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ramser, Kerstin
    Development of a multifunctional microfluidic system for studies of nerve cell activity during hypoxic and anoxic conditions2009In: International Federation for Medical and Biological Engineering Proceedings; 25, 2009, p. 176-179Conference paper (Refereed)
    Abstract [en]

     

    Abstract

    —Hemoproteins usually supply cells and tissue

     with oxygen. A new hemoprotein mainly present in nerve cells called Neuroglobin was recently discovered. Enhanced expression of the protein has been shown to reduce hypoxic neural injury but the mechanism behind this function remains unknown. Methods enabling investigation of the protein in single functional neurons need to be developed. Here, we have studied how the electrical signaling capacity of a neuron was affected by hypoxic environments. Preliminary results show a trend of higher noise-level when a neuron is exposed to hypoxic compared to normoxic surroundings, which implies increased ion-channel activity. The setup used today shows shortages such as reduced control over the oxygen content due to leakage. Therefore, a gas-tight, multifunctional microfluidic system is under development which enables us to study influences of Neuroglobin concentrations on neuronal activity during hypoxia and anoxia. For electrophysiological recordings a patch-clamp micro pipette will be molded into the walls of the microfluidic system. A single biological cell is steered towards the pipette and attached there by means of optical tweezers. The Neuroglobin oxygen binding state will be studied using optical spectroscopy and the neuron environment will be manipulated by applying flows of varying oxygen content through the microfluidic system. This system will constitute a powerful tool in the investigation of the Neuroglobin mechanism of action. 

  • 28.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ovarian steroids in rat and human brain: effects of different endocrine states1987Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain.

    In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated.

    In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex.

    In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5<*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata.

    Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women.

    In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution.

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  • 29.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Hamberg, Jern
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Crenshaw, Albert G
    Sensory adaptation after a 2-week stretching regimen of the rectus femoris muscle2001In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 82, no 9, p. 1245-1250Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the effects of a muscle stretching regimen for the rectus femoris muscle on subjective stretch sensation and range of motion (ROM). DESIGN: A 2 x 2 crossover design comprising 2 treatments and 2 intervention periods. SETTING: A military base in Sweden. PARTICIPANTS: A volunteer sample of 29 male military conscripts divided into 2 groups, with each group subjected to both experimental and control treatments at different time periods. INTERVENTION: Two weeks of supervised stretching (4 times/wk) of the rectus femoris muscle (experimental treatment) and the calf muscles (control treatment). MAIN OUTCOME MEASURES: Subjective rating of the stretch sensation for the anterior aspect of the thigh determined on a category ratio scale. Passive knee flexion ROM determined on each test with the same applied torque, specific for each subject. RESULTS: An additive analysis of variance revealed that the stretch sensation after the experimental treatment was decreased, compared with the control treatment (p <.01). The knee flexion, however, remained the same regardless of the treatment. CONCLUSION: Sensory adaptation seems to be an important mechanistic factor in the effect stretching has on ROM changes. The lack of change in knee flexion suggests that the stretching, as performed in this study, did not influence stiffness of the rectus femoris muscle. Sensory adaptation may also be an underlying mechanism in the alleviating effect of stretching when applied to tired, tender, and painful muscles.

  • 30. Björkman, Sven
    et al.
    Lewander, Tommy
    Karlsson, Jan-Anders
    Koskinen, Lars-Owe D.
    Psychiatric Research Center, Ulleråker Hospital, University of Uppsala, S‐750 17 Uppsala, Sweden.
    Zetterström, Tyra
    Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms.1981In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 33, no 9, p. 580-585Article in journal (Refereed)
    Abstract [en]

    Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.

  • 31.
    Boman, Niklas
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Building muscle: a translation of training adaptation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Training is preparation for what is expected to come through utilization of the plastic and resistive features of nature, known as adaptation. As such, training in humans may have a number of desired goals. These are typically related to sports performance or education. Whatever the goal, a plan needs to be made for reaching it. One needs to identify or select which activities and environments constitute the event or events to which adaptation is sought. Adaptations occurs by imposing something similar to said environment and practicing the selected activities in preparation for the events that can ultimately lead to goal fulfillment.

    One quite common goal of physical training is to achieve a more lean and muscular physique, be it for reasons of performance or esthetics. A leaner and more muscular physique can have many advantages for health and quality of life. If we are to prepare the body’s physical capabilities and properties, they should be utilized in the preparation. By proper design and execution of a program for physical preparation, we set out on the path to achieve the goal.

    A factor that is often highlighted as an important key to building muscle in the human body is the steroid hormone testosterone. According to the hormone hypothesis, increases in muscle mass are achieved through transient elevations in anabolic hormones, such as testosterone and IGF1, induced by physical training. To achieve hypertrophy of the muscles through physical training, one must ensure sure that the muscles get the correct signal, the growth signal, as a result of the training.

    The work presented in this thesis is, in part, an examination of the hormone hypothesis, with both empirical and theoretical elements. The empirical foundations are results of an experiment in which a group of young men were subjected to a program of physical training, designed for all intents and purposes in accordance with contemporary knowledge, to result in muscular hypertrophy in the subjects. The goal was achieved, with an average 4.6% increase in lean body mass in the subjects after the training program. However, there was no evidence that anabolic hormones were elevated at any time during the measurement period.

    The major part of this thesis details a model for explaining the collected observations. It is not intended to merely provide a guide for achieving a leaner more muscular physique but rather is aimed at formulating the problem of inducing the desired adaptations and difficulties involved in approaching the problem. For reasons discussed in this thesis, I do not claim that this is the full and final word on the matter. However, it goes some way toward explaining why, and perhaps how, desired goals should be formulated so that the muscles may understand them.

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  • 32.
    Boman, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Gene expression and fiber type variations in repeated vastus lateralis biopsies2015In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 52, no 2, p. 812-817Article in journal (Refereed)
    Abstract [en]

    Introduction: Muscle sample collection can introduce variation in any measured variable due to inter- and intramuscle variation. We investigated the variation in gene expression and fiber type composition after repeated biopsy sampling from the vastus lateralis muscle. Methods: Six subjects donated 3 tissue samples each. One hour after baseline sampling from 1 vastus lateralis muscle, samples from both vastus lateralis muscles were obtained. Results: The fiber type composition differed between biopsies taken from the same leg. There were no within-subject differences in gene expression between the 3 biopsies. Multivariate analysis supports a model in which gene expression differs significantly between individuals but is not affected by repeated muscle biopsy sampling from the same subject. Conclusion: One vastus lateralis muscle sample per subject is sufficient to establish a reliable baseline for comparing gene expression representing selected pathways over time within the same individual.

  • 33.
    Boman, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åkerfeldt, T
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Effects of protein ingestion on the hormonal response to resistance exercise and increases in lean body mass after eight weeks of trainingManuscript (preprint) (Other academic)
  • 34.
    Brito, Ema C
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Commentary on viewpoint: perspective on the future use of genomics in exercise prescription2008In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 104, no 4, p. 1248-1248Article in journal (Other academic)
  • 35.
    Bytyçi, Ibadete
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Universi College, Pristina, Kosovo, Albania; Clinic of Cardiology, University Clinical Centre of Kosovo, Pristina, Kosovo, Albania.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Universi College, Pristina, Kosovo, Albania.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Molecular and Clinic Research Institute, St George University, and7Brunel University, London, UK.
    Compromised left atrial function and increased size predict raised cavity pressure: a systematic review and meta-analysis2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 5, p. 297-307Article, review/survey (Refereed)
    Abstract [en]

    Aim: This meta-analysis assesses left atrial (LA) cavity and myocardial function measurements that predict pulmonary capillary wedge pressure (PCWP).

    Methods: PubMed-MEDLINE, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry were searched up to December 2018 for studies on the relationship of LA diameter, LA indexed volume (LAVI max, LAVI min), peak atrial longitudinal (PALS), peak atrial contraction (PACS) strain and total emptying fraction (LAEF) with PCWP. Eighteen studies with 1343 patients were included. sensitivity and specificity (with 95% CI) for evaluation of diagnostic accuracy and the best cut-off values for different LA indices in predicting raised PCWP were estimated using summary receiver operating characteristic analysis.

    Results: The pooled analysis showed association between PCWP and LA diameter: Cohen's d = 0 center dot 87, LAVI max: d = 0 center dot 92 and LAVI min: d = 1 center dot 0 (P<0 center dot 001 for all). A stronger correlation was found between PCWP and PALS: d = 1 center dot 26, and PACS: d = 1 center dot 62, total EF d = 1 center dot 22 (P<0 center dot 0001 for all). PALS <= 19% had a summary sensitivity of 80% (65-90) and summary specificity of 77% (52-92), positive likelihood ratio (LR+) 3 center dot 74, negative likelihood ratio (LR-) DOR > 15 center dot 1 whereas LAVI >= 34 ml m(-2) had summary sensitivity of 75% (55-89) and summary specificity 77% (57-90), with LR+ >3, LR- 0 center dot 32 and DOR >10 center dot 1.

    Conclusions: Compromised LA myocardial function and increased size predict raised cavity pressure. These results should assist in optimum follow-up of patients with fluctuating LA pressure.

  • 36.
    Bäckström, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Das, Roshni
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Positive GABAA receptor modulating steroids and their antagonists: Implications for clinical treatments2022In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 34, no 2, article id e13013Article, review/survey (Refereed)
    Abstract [en]

    GABA is the main inhibitory neurotransmitter in the brain and GABAergic transmission has been shown to be of importance for regulation of mood, memory and food intake. The progesterone metabolite allopregnanolone (Allo) is a positive GABAA receptor modulating steroid with potent effects. In humans, disorders such as premenstrual dysphoric disorder (PMDD), hepatic encephalopathy and polycystic ovarian syndrome are associated with elevated Allo levels and increased negative mood, disturbed memory and increased food intake in some individuals. This is surprising because Allo shares many properties with benzodiazepines and is mainly considered to be anxiolytic and anti-depressant. However, it is well established that, in certain individuals, GABAA receptor activating compounds could have paradoxical effects and thus be anxiogenic in low physiological plasma concentrations but anxiolytic at high levels. We have demonstrated that isoallopregnanolone (Isoallo), the 3β-OH sibling of Allo, functions as a GABAA receptor modulating steroid antagonist (GAMSA) but without any effects of its own on GABAA receptors. The antagonistic effect is noted in most GABAA subtypes investigated in vitro to date. In vivo, Isoallo can inhibit Allo-induced anaesthesia in rats, as well as sedation or saccadic eye velocity in humans. Isoallo treatment has been studied in women with PMDD. In a first phase II study, Isoallo (Sepranolone; Asarina Pharma) injections significantly ameliorated negative mood in women with PMDD compared with placebo. Several GAMSAs for oral administration have also been developed. The GAMSA, UC1011, can inhibit Allo induced memory disturbances in rats and an oral GAMSA, GR3027, has been shown to restore learning and motor coordination in rats with hepatic encephalopathy. In humans, vigilance, cognition and pathological electroencephalogram were improved in patients with hepatic encephalopathy on treatment with GR3027. In conclusion GAMSAs are a new possible treatment for disorders and symptoms caused by hyperactivity in the GABAA system.

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  • 37.
    Carlsson, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Desmin-related myopathies in mice and man2001In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, no 3, p. 341-8Article in journal (Refereed)
    Abstract [en]

    Desmin, the main intermediate filament (IF) protein in skeletal and heart muscle cells, is of great importance as a part of the cytoskeleton. The IFs surround and interlink myofibrils, and connect the peripheral myofibrils with the sarcolemma. In myotendinous junctions and neuromuscular junctions of skeletal muscle fibres, desmin is enriched. In the heart, desmin is increased at intercalated discs, the attachment between cardiomyocytes, and it is the main component in Purkinje fibres of the conduction system. Desmin is the first muscle-specific protein to appear during myogenesis. Nevertheless, lack of desmin, as shown from experiments with desmin knockout (K/O) mice, does not influence myogenesis or myofibrillogenesis. However, the desmin knock-out mice postnatally develop a cardiomyopathy and a muscle dystrophy in highly used skeletal muscles. In other skeletal muscles the organization of myofibrils is remarkably unaffected. Thus, the main consequence of the lack of desmin is that the muscle fibres become more susceptible to damage. The loss of membrane integrity leads to a dystrophic process, with degeneration and fibrosis. In the heart cardiac failure develops, whereas in affected skeletal muscles regenerative attempts are seen. In humans, accumulations of desmin have been a hallmark for presumptive desmin myopathies. Recent investigations have shown that some families with such a myopathy have a defect in the gene coding for alphaB-crystallin, whereas others have mutations in the desmin gene. Typical features of these patients are cardiac affections and muscle weakness. Thus, mutations in the desmin gene is pathogenic for a distinct type of muscle disorder.

  • 38. Catoire, MilSNe
    et al.
    Alex, Sheril
    Paraskevopulos, Nicolas
    Mattijssen, Frits
    Evers-van Gogh, Inkie
    Schaart, Gert
    Jeppesen, Jacob
    Kneppers, Anita
    Mensink, Marco
    Voshol, Peter J.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Tan, Nguan Soon
    Hesselink, Matthijs K. C.
    Berbee, Jimmy F.
    Rensen, Patrick C. N.
    Kalkhoven, Eric
    Schrauwen, Patrick
    Kersten, Sander
    Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 11, p. E1043-E1052Article in journal (Refereed)
    Abstract [en]

    Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise encodes angiopoietin-like 4 (ANGPTL4), an inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance. Using a combination of human, animal, and in vitro data, we show that induction of ANGPTL4 in nonexercising muscle is mediated by elevated plasma free fatty acids via peroxisome proliferator-activated receptor-delta, presumably leading to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. In contrast, the induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles. Our data suggest that nonexercising muscle and the local regulation of ANGPTL4 via AMPK and free fatty acids have key roles in governing lipid homeostasis during exercise.

  • 39. Chen, Mengying
    et al.
    Xia, Dongqing
    Min, Cuiting
    Zhao, Xiaoke
    Chen, Yinhua
    Liu, Li
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Li, Xiaonan
    Neonatal repetitive pain in rats leads to impaired spatial learning and dysregulated hypothalamic-pituitary-adrenal axis function in later life2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 39159Article in journal (Refereed)
    Abstract [en]

    Preterm birth is a major health issue. As part of their life-saving care, most preterm infants require hospitalization and are inevitably exposed to repetitive skin-breaking procedures. The long-term effects of neonatal repetitive pain on cognitive and emotional behaviors involving hypothalamic-pituitary-adrenal (HPA) axis function in young and adult rats are unknown. From P8 to P85, mechanical hypersensitivity of the bilateral hindpaws was observed in the Needle group (P < 0.001). Compared with the Tactile group, the Needle group took longer to find the platform on P30 than on P29 (P = 0.03), with a decreased number of original platform site crossings during the probe trial of the Morris water maze test (P = 0.026). Moreover, the Needle group spent more time and took longer distances in the central area than the Tactile group in the Open-field test, both in prepubertal and adult rats (P < 0.05). The HPA axis function in the Needle group differed from the Tactile group (P < 0.05), with decreased stress responsiveness in prepuberty and puberty (P < 0.05) and increased stress responsiveness in adulthood (P < 0.05). This study indicates that repetitive pain that occurs during a critical period may cause severe consequences, with behavioral and neuroendocrine disturbances developing through prepuberty to adult life.

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  • 40. Chen, Nutan
    et al.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    van der Smagt, Patrick
    Estimating Fingertip Forces, Torques, and Local Curvatures from Fingernail Images2020In: Robotica (Cambridge. Print), ISSN 0263-5747, E-ISSN 1469-8668, Vol. 38, no 7, p. 1242-1262Article in journal (Refereed)
    Abstract [en]

    The study of dexterous manipulation has provided important insights into human sensorimotor control as well as inspiration for manipulation strategies in robotic hands. Previous work focused on experimental environment with restrictions. Here, we describe a method using the deformation and color distribution of the fingernail and its surrounding skin to estimate the fingertip forces, torques, and contact surface curvatures for various objects, including the shape and material of the contact surfaces and the weight of the objects. The proposed method circumvents limitations associated with sensorized objects, gloves, or fixed contact surface type. In addition, compared with previous single finger estimation in an experimental environment, we extend the approach to multiple finger force estimation, which can be used for applications such as human grasping analysis. Four algorithms are used, c.q., Gaussian process, convolutional neural networks, neural networks with fast dropout, and recurrent neural networks with fast dropout, to model a mapping from images to the corresponding labels. The results further show that the proposed method has high accuracy to predict force, torque, and contact surface.

  • 41.
    Chizhov, Anton V
    et al.
    Computational Physics Laboratory, Division of Plasma Physics, Atomic Physics and Astrophysics, A.F. Ioffe Physical-Technical Institute of the Russian Academy of Sciences, St. Petersburg, Russia.
    Malinina, Evgenia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Department of Neurodynamics and Neurobiology, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
    Graham, Lyle J
    Neurophysiology and New Microscopies Laboratory, INSERM U603 - CNRS UMR 8154, Université Paris Descartes, Paris, France.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Firing clamp: a novel method for single-trial estimation of excitatory and inhibitory synaptic neuronal conductances.2014In: Frontiers in Cellular Neuroscience, E-ISSN 1662-5102, Vol. 8, no 86, p. 86-Article in journal (Refereed)
    Abstract [en]

    Understanding non-stationary neuronal activity as seen in vivo requires estimation of both excitatory and inhibitory synaptic conductances from a single trial of recording. For this purpose, we propose a new intracellular recording method, called "firing clamp." Synaptic conductances are estimated from the characteristics of artificially evoked probe spikes, namely the spike amplitude and the mean subthreshold potential, which are sensitive to both excitatory and inhibitory synaptic input signals. The probe spikes, timed at a fixed rate, are evoked in the dynamic-clamp mode by injected meander-like current steps, with the step duration depending on neuronal membrane voltage. We test the method with perforated-patch recordings from isolated cells stimulated by external application or synaptic release of transmitter, and validate the method with simulations of a biophysically-detailed neuron model. The results are compared with the conductance estimates based on conventional current-clamp recordings.

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  • 42.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Otten, Julia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Waling, Maria
    Umeå University, Faculty of Social Sciences, Department of Food, Nutrition and Culinary Science.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Improved peripheral and hepatic insulin sensitivity after lifestyle interventions in type 2 diabetes is associated with specific metabolomic and lipidomic signatures in skeletal muscle and plasma2021In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 11, no 12, article id 834Article in journal (Refereed)
    Abstract [en]

    Lifestyle interventions with weight loss can improve insulin sensitivity in type 2 diabetes (T2D), but mechanisms are unclear. We explored circulating and skeletal muscle metabolite signatures of altered peripheral (pIS) and hepatic insulin sensitivity (hIS) in overweight and obese T2D individuals that were randomly assigned a 12-week Paleolithic-type diet with (diet-ex, n = 13) or without (diet, n = 13) supervised exercise. Baseline and post-intervention measures included: mass spectrometry-based metabolomics and lipidomics of skeletal muscle and plasma; pIS and hIS; ectopic lipid deposits in the liver and skeletal muscle; and skeletal muscle fat oxidation rate. Both groups lowered BMI and total % fat mass and increased their pIS. Only the diet-group improved hIS and reduced ectopic lipids in the liver and muscle. The combined improvement in pIS and hIS in the diet-group were associated with decreases in muscle and circulating branched-chain amino acid (BCAA) metabolites, specifically valine. Improved pIS with diet-ex was instead linked to increased diacylglycerol (34:2) and triacylglycerol (56:0) and decreased phosphatidylcholine (34:3) in muscle coupled with improved muscle fat oxidation rate. This suggests a tissue crosstalk involving BCAA-metabolites after diet intervention with improved pIS and hIS, reflecting reduced lipid influx. Increased skeletal muscle lipid utilization with exercise may prevent specific lipid accumulation at sites that perturb insulin signaling.

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  • 43. Cipriani, Christian
    et al.
    Segil, Jacob L.
    Clemente, Francesco
    Weir, Richard F. Ff.
    Edin, Benoni
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Humans can integrate feedback of discrete events in their sensorimotor control of a robotic hand2014In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 232, no 11, p. 3421-3429Article in journal (Refereed)
    Abstract [en]

    Providing functionally effective sensory feedback to users of prosthetics is a largely unsolved challenge. Traditional solutions require high band-widths for providing feedback for the control of manipulation and yet have been largely unsuccessful. In this study, we have explored a strategy that relies on temporally discrete sensory feedback that is technically simple to provide. According to the Discrete Event-driven Sensory feedback Control (DESC) policy, motor tasks in humans are organized in phases delimited by means of sensory encoded discrete mechanical events. To explore the applicability of DESC for control, we designed a paradigm in which healthy humans operated an artificial robot hand to lift and replace an instrumented object, a task that can readily be learned and mastered under visual control. Assuming that the central nervous system of humans naturally organizes motor tasks based on a strategy akin to DESC, we delivered short-lasting vibrotactile feedback related to events that are known to forcefully affect progression of the grasp-lift-and-hold task. After training, we determined whether the artificial feedback had been integrated with the sensorimotor control by introducing short delays and we indeed observed that the participants significantly delayed subsequent phases of the task. This study thus gives support to the DESC policy hypothesis. Moreover, it demonstrates that humans can integrate temporally discrete sensory feedback while controlling an artificial hand and invites further studies in which inexpensive, noninvasive technology could be used in clever ways to provide physiologically appropriate sensory feedback in upper limb prosthetics with much lower band-width requirements than with traditional solutions.

  • 44. Crenshaw, Albert G
    et al.
    Elcadi, Guilherme H
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Hellström, Fredrik
    Mathiassen, Svend Erik
    Reliability of near-infrared spectroscopy for measuring forearm and shoulder oxygenation in healthy males and females2012In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 112, no 7, p. 2703-2715Article in journal (Refereed)
    Abstract [en]

    This study determined the day-to-day reliability of NIRS-derived oxygenation responses (a dagger StO(2)%) for isometric contractions and for cuff occlusion. Twenty-four subjects (12 males and 12 females) were tested for 2 days (4-6 days interval). Variables generated were: (1) a dagger StO(2)% for isometric contractions (10, 30, 50 and 70% MVC) for descending trapezius (TD) and extensor carpi radialis (ECR) muscles; (2) slope changes in total haemoglobin (HbTslope) and deoxyhaemoglobin (HHbslope) for the ECR using upper arm venous (VO, 50 mmHg) and arterial occlusion (AO, 250 mmHg); (3) recovery slopes (Rslope) for oxygen saturation (StO(2)) following isometric contractions and AO. For each variable, an intraclass correlation (ICC) was calculated to assess the ability to differentiate between subjects, and limits of agreement (LOA) were computed to assess day-to-day consistency of the measurement. ICCs for Delta StO(2)% were lowest at 10% MVC for both ECR (0.58) and TD (0.55), and highest at 30% MVC for ECR (0.95) and at 70% MVC for TD (0.79). For both muscles, LOA for Delta StO(2)% was lowest at 10% and highest at 50 and 70% MVC. ICC for HbTslope was 0.17. For HHbslope ICC was higher for AO (0.83) than for VO (0.73), and LOA was lower for AO. For the ECR Rslope ICCs ranged from 0.88 to 0.90 for contraction, but was lower for AO (0.33); LOA was lowest at 70% MVC. For trapezius Rslope ICCs ranged from 0.63 to 0.73 and LOA was lowest at 30% MVC. For this study, establishing reliability data for the ECR and TD and including variables commonly reported are expected to have meaning for future NIRS studies of work-related upper-extremity pain as well as for other NIRS research and clinical applications.

  • 45.
    Dahlin, Erika
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Train your brain: updating, transfer, and neural changes2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An initial aim of this thesis was to determine whether training of a specific executive function (updating) produces improvements in performance on trained and transfer tasks, and whether the effects are maintained over time. Neural systems underlying training and transfer effects were also investigated and one question considered is whether transfer depends on general or specific neural overlap between training and transfer tasks. An additional aim was to identify how individual differences in executive functioning are mapped to functional brain changes. In Study I, significant training-related changes in performance on the letter memory criterion task were found in both young and older adults after 5 weeks of updating training. Transfer to a 3-back test of updating was also demonstrated in the young adults. Functional Magnetic Resonance Imaging (fMRI) revealed overlapping activity in letter memory and 3-back tasks in fronto-parietal areas and striatum pre-training, and a joint training-related activity increase for the tasks in a striatal region. No transfer was observed to a task (Stroop) that engaged fronto-parietal areas, but not the striatal region and updating per se. Moreover, age-related striatal changes imposed constraints on transfer. In Study II, additional transfer tasks and a test of long-term maintenance were included. Results revealed that training-related gains in performance were maintained 18 months post-training in both young and older adults, whereas transfer effects were limited to tasks requiring updating and restricted to young participants. In Study III, analyses of brain activity and performance during n-back (1/2/3-back) were executed. This task enables manipulation of executive demand, which permits examination of how individual differences in executive functioning can be mapped to functional brain changes. Relative to a young high-

    performing group, capacity constraints in executive functioning were apparent between 1–2-back for the elderly participants and between 2–3-back for a young low-performing group. Capacity constraints in neural activity followed this pattern by showing a monotonically increasing response in the parietal cortex and the thalamus for young high performers, whereas activity levelled off at 1-back for elderly performers and at 2-back for young low performers. The response in the dorsal frontal cortex followed a similar pattern. Together, these findings indicate that fronto-parietal as well as sub-cortical areas are important for individual differences in executive functioning, training of updating and transfer effects.

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  • 46. Dahlman, Anna Sjors
    et al.
    Jonsdottir, Ingibjorg H.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Burnout patients' metabolic responses to acute stress2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, p. 24-25Article in journal (Other academic)
  • 47.
    Das, Roshni
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umecrine AB, Norrlands University Hospital Umeå, Umeå, Sweden.
    Ragagnin, Gianna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Sjöstedt, Jessica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umecrine AB, Norrlands University Hospital Umeå, Umeå, Sweden.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Department of Nursing Sciences, Mid Sweden University, Sundsvall, Sweden; Umecrine AB, Norrlands University Hospital Umeå, Umeå, Sweden.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umecrine AB, Norrlands University Hospital Umeå, Umeå, Sweden.
    Medroxyprogesterone acetate positively modulates specific GABAA-receptor subtypes - affecting memory and cognition2022In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 141, article id 105754Article in journal (Refereed)
    Abstract [en]

    Medroxyprogesterone acetate (MPA) is a progestin widely used in humans as hormone replacement therapy and at other indications. Many progestin metabolites, as the progesterone metabolite allopregnanolone, have GABAA-receptor modulatory effects and are known to affect memory, learning, appetite, and mood. In women, 4 years chronic treatment with MPA doubles the frequency of dementia and in rats, MPA causes cognitive impairment related to the GABAergic system. Activation of the membrane bound GABAA receptor results in a chloride ion flux that can be studied by whole-cell patch-clamp electrophysiological recordings. The purpose of this study was to clarify the modulatory effects of MPA and specific MPA metabolites, with structures like known GABAA-receptor modulators, on different GABAA-receptor subtypes. An additional aim was to verify the results as steroid effects on GABA response in single cells taken from rat hypothalamus. HEK-293 cell-lines permanently expressing the recombinant human GABAA-receptor subtype α1β2γ2L or α5β3γ2L or α2β3γ2S were created. The MPA metabolites 3α5α-MPA,3β5α-MPA and 3β5β-MPA were synthesised and purified for electrophysiological patch-clamp measurements with a Dynaflow system. The effects of MPA and tetrahydrodeoxycorticosterone were also studied. None of the studied MPA metabolites affected the responses mediated by α1β2γ2L or α5β3γ2L GABAA receptors. Contrary, MPA clearly acted both as a positive modulator and as a direct activator of the α5β3γ2L and α2β3γ2S GABAA receptors. However, in concentrations up to 10 μM, MPA was inactive at the α1β2γ2L GABAA receptor. In the patch-clamp recordings from dissociated cells of the preoptic area in rats, MPA increased the amplitude of responses to GABA. In addition, MPA alone without added GABA, evoked a current response. In conclusion, MPA acts as a positive modulator of specific GABAA receptor subtypes expressed in HEK cells and at native GABA receptors in single cells from the hypothalamic preoptic area.

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  • 48. Delhaye, Benoit
    et al.
    Barrea, Allan
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Lefèvre, Philippe
    Thonnard, Jean-Louis
    Surface strain measurements of fingertip skin under shearing2016In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 13, no 115, article id 20150874Article in journal (Refereed)
    Abstract [en]

    The temporal evolution of surface strain, resulting from a combination of normal and tangential loading forces on the fingerpad, was calculated from high-resolution images. A customized robotic device loaded the fingertip with varying normal force, tangential direction and tangential speed. We observed strain waves that propagated from the periphery to the centre of the contact area. Consequently, different regions of the contact area were subject to varying degrees of compression, stretch and shear. The spatial distribution of both the strains and the strain energy densities depended on the stimulus direction. Additionally, the strains varied with the normal force level and were substantial, e.g. peak strains of 50% with a normal force of 5 N, i.e. at force levels well within the range of common dexterous manipulation tasks. While these observations were consistent with some theoretical predictions from contact mechanics, we also observed substantial deviations as expected given the complex geometry and mechanics of fingertips. Specifically, from in-depth analyses, we conclude that some of these deviations depend on local fingerprint patterns. Our data provide useful information for models of tactile afferent responses and background for the design of novel haptic interfaces.

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  • 49.
    Delhaye, Benoit P.
    et al.
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    Jarocka, Ewa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Barrea, Allan
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    Thonnard, Jean-Louis
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lefèvre, Philippe
    Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve, Belgium; Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
    High-resolution imaging of skin deformation shows that afferents from human fingertips signal slip onset2021In: eLIFE, E-ISSN 2050-084X, Vol. 10, article id e64679Article in journal (Refereed)
    Abstract [en]

    Human tactile afferents provide essential feedback for grasp stability during dexterous object manipulation. Interacting forces between an object and the fingers induce slip events that are thought to provide information about grasp stability. To gain insight into this phenomenon, we made a transparent surface slip against a fixed fingerpad while monitoring skin deformation at the contact. Using microneurography, we simultaneously recorded the activity of single tactile afferents innervating the fingertips. This unique combination allowed us to describe how afferents respond to slip events and to relate their responses to surface deformations taking place inside their receptive fields. We found that all afferents were sensitive to slip events, but FA-I afferents in particular faithfully encoded compressive strain rates resulting from those slips. Given the high density of FA-I afferents in fingerpads, they are well suited to detect incipient slips and to provide essential information for the control of grip force during manipulation.

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  • 50. Diamond, Jonathan S.
    et al.
    Nashed, Joseph Y.
    Johansson, Roland S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Wolpert, Daniel M.
    Flanagan, J. Randall
    Rapid Visuomotor Corrective Responses during Transport of Hand-Held Objects Incorporate Novel Object Dynamics2015In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 29, p. 10572-10580Article in journal (Refereed)
    Abstract [en]

    Numerous studies have shown that people are adept at learning novel object dynamics, linking applied force and motion, when performing reaching movements with hand-held objects. Here we investigated whether the control of rapid corrective arm responses, elicited in response to visual perturbations, has access to such newly acquired knowledge of object dynamics. Participants first learned to make reaching movements while grasping an object subjected to complex load forces that depended on the distance and angle of the hand from the start position. During a subsequent test phase, we examined grip and load force coordination during corrective arm movements elicited (within similar to 150 ms) in response to viewed sudden lateral shifts (1.5 cm) in target or object position. We hypothesized that, if knowledge of object dynamics is incorporated in the control of the corrective responses, grip force changes would anticipate the unusual load force changes associated with the corrective arm movements so as to support grasp stability. Indeed, we found that the participants generated grip force adjustments tightly coupled, both spatially and temporally, to the load force changes associated with the arm movement corrections. We submit that recently learned novel object dynamics are effectively integrated into sensorimotor control policies that support rapid visually driven arm corrective actions during transport of hand held objects.

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