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  • 51.
    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, 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.

  • 52. 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.

  • 53. Clemente, Francesco
    et al.
    D'Alonzo, Marco
    Controzzi, Marco
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Cipriani, Christian
    Non-Invasive, Temporally Discrete Feedback of Object Contact and Release Improves Grasp Control of Closed-Loop Myoelectric Transradial Prostheses2016In: IEEE transactions on neural systems and rehabilitation engineering, ISSN 1534-4320, E-ISSN 1558-0210, Vol. 24, no 12, p. 1314-1322Article in journal (Refereed)
    Abstract [en]

    Human grasping and manipulation control critically depends on tactile feedback. Without this feedback, the ability for fine control of a prosthesis is limited in upper limb amputees. Although various approaches have been investigated in the past, at present there is no commercially available device able to restore tactile feedback in upper limb amputees. Based on the Discrete Event-driven Sensory feedback Control (DESC) policy we present a device able to deliver short-lasting vibrotactile feedback to transradial amputees using commercially available myoelectric hands. The device (DESC-glove) comprises sensorized thimbles to be placed on the prosthesis digits, a battery-powered electronic board, and vibrating units embedded in an arm-cuff being transiently activated when the prosthesis makes and breaks contact with objects. The consequences of using the DESC-glove were evaluated in a longitudinal study. Five transradial amputees were equipped with the device for onemonth at home. Through a simple test proposed here for the first time-the virtual eggs test-we demonstrate the effectiveness of the device for prosthetic control in daily life conditions. In the future the device could be easily exploited as an add-on to complement myoelectric prostheses or even embedded in prosthetic sockets to enhance their control by upper limb amputees.

  • 54.
    Dagberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Improved organotypic cell culture model for analysis of the neuronal circuit involved in the monosynaptic stretch reflex.2006In: Journal of Neuroscience Research, ISSN 0360-4012, Vol. 84, no 2, p. 460-9Article in journal (Refereed)
    Abstract [en]

    Knowledge regarding neuronal circuit formation is central for the understanding of the vast network making up the brain. It is therefore necessary to find novel ways to analyze the mechanisms involved in well-defined neural circuits. We present an improved in vitro model of the monosynaptic stretch reflex circuit, based on primary organotypic cell cultures. By using limb tissue as a source of muscle fibers instead of circumspinal tissue we could make the in vitro system more in vivo like in the sense that it focuses on the stretch reflex involving limb muscles. Furthermore, our analyses showed that this procedure allows muscle fibers to follow the normal developmental pattern. Particularly interesting was the finding of slow tonic myosin heavy chain expressing muscle fibers, a developmental marker for muscle spindles, in the cultures showing that this system has the potential to contain the complete reflex circuits.

  • 55.
    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.

  • 56.
    Damber, Jan-Erik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Testicular blood flow: methodological and functional studies in the rat1978Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Different methods of measuring testicular blood flow in the rat were compared in an attempt to find an accurate method for measuring physiological testicular blood flow. It was found that both the Xenon- 133 clearance technique and the radioactive microsphere technique probably reflect true physiological blood flow in the testis.

    The microsphere method was used to study some functional aspects of testicular blood flow. There was a significant positive correla­tion between the testicular blood flow and the outflow of testosterone in the spermatic vein, indicating that testicular hormone secretion may be affected indirectly via a primary effect on testicular blood flow. Intra-arterial infusion of LH caused a significant decrease in the vascular resistance of the testis. However, the effect was small in comparison with the simultaneous effect of LH on plasma testosterone concentration, indicating that blood flow changes are not critically involved in the acute effect of LH on testicular endocrine function. Infusion of epinephrine or norepinephrine did not induce any absolute changes in testicular blood flow, but norepinephrine caused an in­crease in testicular vascular resistance. Both catecholamines caused significant depressions in plasma testosterone concentration. It was concluded that the catecholamine induced reductions in testosterone concentration were not due to a vascular effect on the testis.

    Testicular blood flow and Leydig cell function in the cryptorchid and heated testis were also studied. There was a significant increase in relative blood flow in the cryptorchid testis, probably due to an highly altered morphology consisting of a relative increase in inter­stitial tissue containing blood vessels. Furthermore, it was found that the testosterone levels, in spermatic vein blood from the cryptor­chid testis, were highly reduced in comparison to the corresponding values for the scrotal testis and the outflow of testosterone from the cryptorchid testis was estimated to be only 13% of that from the scrotal one. This result suggested that the Leydig cell function was greatly impaired in the cryptorchid testis. The vasculature of the testis is relatively insensitive to local heating since no effects on vascular resistance were observed when warming the testis to ab­dominal temperature. On the other hand, there was a significant in­crease in blood flow in the testis at 41 and 43° C, which are tempera­tures known to induce cessation of spermatogenesis in the rat. The acute response of the testis to LH stimulation was reduced when warm­ing the scrotum to 41 and 43° C. This strongly indicates an impaired Leydig cell function at these temperatures. Since blood flow was in­creased at these temperatures it was concluded that the reduced Leydig cell responsiveness to LH was unrelated to testicular perfusion.

  • 57. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Chowdhury, Rumana
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dolan, Raymond J.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Backman, Lars
    Guitart-Masip, Marc
    Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 1, p. 261-270Article in journal (Refereed)
    Abstract [en]

    Learning to act to obtain reward and inhibit to avoid punishment is easier compared with learning the opposite contingencies. This coupling of action and valence is often thought of as a Pavlovian bias, although recent research has shown it may also emerge through instrumental mechanisms. We measured this learning bias with a rewarded go/no-go task in 60 adults of different ages. Using computational modeling, we characterized the bias as being instrumental. To assess the role of endogenous dopamine (DA) in the expression of this bias, we quantified DA D1 receptor availability using positron emission tomography (PET) with the radioligand [11C]SCH23390. Using principal-component analysis on the binding potentials in a number of cortical and striatal regions of interest, we demonstrated that cortical, dorsal striatal, and ventral striatal areas provide independent sources of variance in DA D1 receptor availability. Interindividual variation in the dorsal striatal component was related to the strength of the instrumental bias during learning. These data suggest at least three anatomical sources of variance in DA D1 receptor availability separable using PET in humans, and we provide evidence that human dorsal striatal DA D1 receptors are involved in the modulation of instrumental learning biases.

  • 58.
    de Frias, Cindy M
    et al.
    Stockholm University.
    Marklund, Petter
    Stockholm University, Stockholm Brain Institute.
    Eriksson, Elias
    Göteborg University.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Öman, Lena
    Umeå University.
    Annerbrink, Kristina
    Göteborg University.
    Bäckman, Lars
    Karolinska Institute.
    Nilsson, Lars-Göran
    Stockholm University.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Influence of COMT gene polymorphism on fMRI-assessed sustained and transient activity during a working memory task.2010In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 22, no 7, p. 1614-1622Article in journal (Refereed)
    Abstract [en]

    The catechol O-methyltransferase (COMT) gene--encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)--contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.

  • 59. 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.

  • 60. 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.

  • 61.
    Dimitriou, M
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Discharges in Human Muscle Receptor Afferents during Block Grasping2008In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 28, no 48, p. 12632-12642Article in journal (Refereed)
  • 62.
    Dimitriou, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Enhanced Muscle Afferent Signals during Motor Learning in Humans2016In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 26, no 8, p. 1062-1068Article in journal (Refereed)
    Abstract [en]

    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "gamma" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning.

  • 63.
    Dimitriou, Michael
    et al.
    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.
    Human muscle spindles act as forward sensory models2010In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 20, no 19, p. 1763-1767Article in journal (Refereed)
    Abstract [en]

    Modern theories of motor control incorporate forward models that combine sensory information and motor commands to predict future sensory states. Such models circumvent unavoidable neural delays associated with on-line feedback control. Here we show that signals in human muscle spindle afferents during unconstrained wrist and finger movements predict future kinematic states of their parent muscle. Specifically, we show that the discharges of type Ia afferents are best correlated with the velocity of length changes in their parent muscles approximately 100-160 ms in the future and that their discharges vary depending on motor sequences in a way that cannot be explained by the state of their parent muscle alone. We therefore conclude that muscle spindles can act as "forward sensory models": they are affected both by the current state of their parent muscle and by efferent (fusimotor) control, and their discharges represent future kinematic states. If this conjecture is correct, then sensorimotor learning implies learning how to control not only the skeletal muscles but also the fusimotor system.

  • 64.
    Domellöf, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ekman, Urban
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Elgh, Eva
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Cognitive function in the early phase of Parkinson's disease, a longitudinal follow-upManuscript (preprint) (Other academic)
  • 65.
    Druzin, Michael
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Haage, David
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Bicuculline free base blocks voltage-activated K+ currents in rat medial preoptic neurons.2004In: Neuropharmacology, ISSN 0028-3908, Vol. 46, no 2, p. 285-95Article in journal (Refereed)
    Abstract [en]

    The effects of the well-known GABA(A)-receptor blocker bicuculline on voltage-gated K(+) currents were studied in neurons from the medial preoptic nucleus (MPN) of rat. Whole-cell currents were recorded using the perforated-patch technique. Voltage steps from -54 to +6 mV resulted in tetraethylammonium-sensitive K(+) currents of delayed rectifier type. The total K(+) current (at 300 ms), including Ca(2+)-dependent and Ca(2+)-independent components, was reversibly reduced (17 +/- 4%) by 100 microM bicuculline methiodide and (37 +/- 5%) by 100 microM bicuculline as free base. The Ca(2+)-independent fraction (77 +/- 2%) of K(+) current evoked by a voltage step was, however, reduced (54 +/- 6%) only by bicuculline free base, but was not affected by bicuculline methiodide. The half-saturating concentration of bicuculline free base for blocking this purely voltage-gated K(+) current was 113 microM, whereas for blocking a steady Ca(2+)-dependent K(+) current it was 36 microM. The bicuculline-sensitive voltage-gated K(+) current was composed of 4-AP-sensitive and 4-AP-resistant components with different kinetic properties. No component of the purely voltage-gated K(+) current was affected neither by 100 nM alpha-dendrotoxin nor by 100 nM I-dendrotoxin. The possible K(+)-channel subtypes mediating the bicuculline-sensitive current in MPN neurons are discussed.

  • 66.
    Druzin, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals.2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no Pt 1, p. 131-46Article in journal (Refereed)
    Abstract [en]

    Calcium influx into the presynaptic nerve terminal is well established as a trigger signal for transmitter release by exocytosis. By studying dissociated preoptic neurons with functional adhering nerve terminals, we here show that presynaptic Ca2+ influx plays dual and opposing roles in the control of spontaneous transmitter release. Thus, application of various Ca2+ channel blockers paradoxically increased the frequency of spontaneous (miniature) inhibitory GABA-mediated postsynaptic currents (mIPSCs). Similar effects on mIPSC frequency were recorded upon washout of Cd2+ or EGTA from the external solution. The results are explained by a model with parallel Ca2+ influx through channels coupled to the exocytotic machinery and through channels coupled to Ca2+-activated K+ channels at a distance from the release site.

  • 67.
    Druzin, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Grimsholm, Ola
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons.2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, p. e20213-Article in journal (Refereed)
    Abstract [en]

    The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K(+) channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K(+) channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-Estradiol rapidly (within seconds) and reversibly reduced the K(+) currents, showing an EC(50) value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca(2+), and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K(+) currents, membrane-impermeant forms of estradiol did not reduce the K(+) currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the K(V)-2-channel blocker r-stromatoxin-1. The time course of K(+) current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K(+), suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K(+) channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K(+) currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels.

  • 68.
    Edin, Benoni
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Assigning biological functions: Making sense of causal chains2008In: Synthese, ISSN 0039-7857, E-ISSN 1573-0964, Vol. 161, no 2, p. 203-218Article in journal (Refereed)
  • 69.
    Edin, Benoni
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Quantitative analyses of dynamic strain sensitivity in human skin mechanoreceptors.2004In: Journal of Neurophysiology, ISSN 0022-3077, Vol. 92, no 6, p. 3233-43Article in journal (Refereed)
    Abstract [en]

    Microneurographical recordings from 24 slowly adapting (SA) and 16 fast adapting (FA) cutaneous mechanoreceptor afferents were obtained in the human radial nerve. Most of the afferents innervated the hairy skin on the back of the hand. The afferents' receptive fields were subjected to controlled strains in a ramp-and-hold fashion with strain velocities from 1 to 64%.s(-1), i.e., strain velocities within most of the physiological range. For all unit types, the mean variation in response onset approached 1 ms for strain velocities >8%.s(-1). Except at the highest strain velocities, the first spike in a typical SAIII unit was evoked at strains <0.5% and a typical SAII unit began to discharge at <1% skin strain. Skin strain velocity had a profound effect on the discharge rates of all classes of afferents. The "typical" peak discharge rate at the highest strain velocity studied was 50-95 imp/s(-1) depending on unit type. Excellent fits were obtained for both SA and FA units when their responses to ramp stretches were modeled by simple power functions (r2 > 0.9 for 95% of the units). SAIII units grouped with SAII with respect to onset latency and onset variation but with SAI units with respect to dynamic strain sensitivity. Because both SA and FA skin afferents respond strongly, quickly, and accurately to skin strain changes, they all seem to be able to provide useful information about movement-related skin strain changes and therefore contribute to proprioception and kinesthesia.

  • 70.
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Classification of muscle stretch receptor afferents in humans1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The response patterns of human stretch receptors in the finger extensor muscles of the forearm were studied using the microneurography technique. Single-unit recordings were obtained from one-hundred and twenty-four afferents. A procedure was developed to classify the units in muscle spindle primary afferents, secondary afferents, and Golgi tendong organ afferents. The procedure allows an objective and reproducible classification on the basis of the afferents’ responses to a series of tests which individually are non-conclusive.

    It was demonstrated that maximal twitch contractions can be elicited in the finger extensor muscles of the forearm, without causing undue discomfort to the subjects, or hazarding the single-unit recording. The response of the units to this test allowed, in most cases but not always, a separation in muscle spindle and tendon organ afferents. Thus the test was not adequate for an unequivocal classification.

    Three discrete response parameters were extracted from ramp-and-hold stretches, viz. the presence or absence of an initial burst and a deceleration response, and prompt silencing at slow muscle shortening. The distributions of the parameters were significantly different among the three unit types. These parameters which were pair-wise independent constituted a set of considerable discriminative power. It was shown that human muscle spindles have about the same static position sensitivity to fractional muscle stretch as previously found in animals.

    Stretch sensitization was demonstrated by rapid, repeated stretches of the muscle which enhanced the réponse to subsequent slow stretches of muscle spindles. Sensitization was different with primary and secondary muscle spindle afferents whereas Golgi tendon organ afferents never displayed stretch sensitization.

    One-to-one driving with small-amplitude sinusoidal stretches superimposed on ramp-and- hold stretches was almost exclusively seen with primary muscle spindle afferents, whereas secondaries seldom and tendon organ afferents never displayed driving.

    The afferent responses during slowly increasing isometric contractions and rapid relaxations were analysed. An increased discharge rate on relaxation was common among spindle afferents whereas it was never seen in tendon organs afferents. Two separate groups of spindles afferents were found with regard to fusimotor recruitment. The largest group was recruited at rather low and variable contractile forces whereas the smaller group was not recruited at all.

    The proportions of the three unit types, spindle primary, spindle secondary, and Golgi tendon organ afferents were estimated from a preliminary classification and the distribution of the eight response features were analyzed for each class of afferents. On the basis of these estimates and the response pattern of the individual unit Bayes’ theorem was used to calculate the probabilities that the unit was a spindle primary, a spindle secondary, or a tendon organ afferent. Estimates indicate that about 19 out of 20 muscle afferents are correctly classified when all eight features are analyzed.

  • 71.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Cutaneous afferents provide information about knee joint movements in humans.2001In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 531, no Pt 1, p. 289-297Article in journal (Refereed)
    Abstract [en]

    1. Neurophysiological evidence that afferent information from skin receptors is important for proprioception has been gathered mainly in experiments relating to the human hand and finger joints. To investigate if proprioceptive information is also provided by skin mechanoreceptor afferents from skin areas related to large joints of postural importance, microneurography recordings were obtained in humans from skin afferents in the lateral cutaneous femoral nerve to study their responses to knee joint movements. 2. Data were collected from 60 sequentially recorded afferents from slowly (n = 23) and fast (n = 6) adapting low-threshold mechanoreceptors, hair follicle receptors (n = 24), field receptors (n = 1) and C mechanoreceptors (n = 6). Fascicular recordings showed that the lateral cutaneous femoral nerve supplies extensive areas of the thigh: from 5-10 cm below the inguinal ligament down to below and lateral to the knee joint; accordingly, the afferents originated in receptors located in wide areas of the human thigh. 3. All afferents from fast and slowly adapting low-threshold mechanoreceptors, as well as C mechanoreceptors, responded to manually applied skin stretch. In contrast, the same stimulus elicited, at most, feeble responses in hair follicle receptors. 4. Qualitative and quantitative analyses of the responses of a subset of afferents revealed that in particular slowly adapting afferents effectively encode both static and dynamic aspects of passively imposed knee joint movements. 5. It was concluded that receptors in the hairy skin of humans can provide high-fidelity information about knee joint movements. A previously undefined type of slowly adapting receptor (SA III) seemed particularly suited for this task whereas this does not seem to be the case for either hair follicle receptors or C mechanoreceptors.

  • 72.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Finger joint movement sensitivity of non-cutaneous mechanoreceptor afferents in the human radial nerve.1990In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 82, no 2, p. 417-422Article in journal (Refereed)
    Abstract [en]

    The responses of non-cutaneous receptors in the human hand to normal digit movements were studied using single afferent recordings from the radial nerve. Eight joint-related afferents had thresholds of 50 mN or less. All responded to passive flexion movements within the physiological range of joint rotation and showed predominantly static response sensitivity; none increased its discharge during passive extension. However, only two of these eight afferents showed the same response pattern during active movements; three discharged only during the extension phase whereas the other three discharged both during extension and flexion. No high-threshold, joint-related mechanoreceptive afferents were encountered in a population of 148 afferents recorded from the cutaneous portion of the radial nerve indicating a scarcity of such afferents on the dorsal aspect of finger joints. Seven high-threshold, subcutaneous mechanoreceptive units not related to joints had thresholds for indentations of 50 mN or more and lacked responses to finger movements. Low-threshold mechanoreceptive afferents related to joints in the human hand may thus provide kinematic information in the physiological mid-range of both passive and active movements. Joint position cannot, however, be derived unambiguously from their discharge since the receptor responses may be dramatically altered by muscle activity.

  • 73.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Quantitative analysis of static strain sensitivity in human mechanoreceptors from hairy skin.1992In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 67, no 5, p. 1105-1113Article in journal (Refereed)
    Abstract [en]

    1. Microelectrode recordings from 15 slowly adapting (SA) cutaneous mechanoreceptor afferents originating in hairy skin were obtained from the radial nerve in humans. 2. Controlled skin stretch was applied to the back of the hand that encompassed the physiological range of skin stretch during movements at the metacarpophalangeal (MCP) joints. 3. Both SA Group I and II afferents showed exquisite dynamic and static sensitivity to skin stretch. The median static strain sensitivity was 1.0 imp.s-1 per percent skin stretch for SAI units and 1.8 for SAII units. 4. Translated into sensitivity to movements at the MCP joint, both SAI and SAII afferents in the skin of the back of the hand displayed a positional sensitivity that was comparable with that reported for muscle spindle afferents. 5. These data give quantitative support to suggestions that skin receptors in the human hairy skin provide information on nearby joint configurations and therefore may play a specific role in proprioception, kinesthesia, and motor control.

  • 74.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    The 'initial burst' of human primary muscle spindle afferents has at least two components.1991In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 143, no 2, p. 169-175Article in journal (Refereed)
    Abstract [en]

    Ten muscle spindle primary afferents from the extensor digitorum communis muscle of man were studied with single unit afferent recordings. Responses to slow test stretches with three different pre-history conditions were assessed to investigate the contribution of rapid stretches to the stretch sensitization phenomenon. In two of the conditions, the slow test ramps were preceded by rapid stretch after which the parent muscle of the receptor was either (a) kept short for 5 seconds or (b) kept long for 3.2 seconds and then returned to the short muscle length for 5 seconds. The third condition (c) consisted of a slow stretch from short to long muscle length followed by a rapid return to the short muscle length, in turn followed by 5 seconds at the short muscle length. Afferent responses were depressed when the muscle had been kept at the long length after the rapid stretches (condition b) and enhanced when the muscle had been kept at the short length (conditions a & c). A prominent 'initial burst' was only present in the afferent discharge when the parent muscles of the primary endings had been kept short (condition a). A second, more prolonged burst was present for conditions (a) and (c) but was lacking or inconspicuous when the muscle had been kept long after rapid stretches (condition b). The rapid stretches in the stretch sensitization paradigm appear to be a primary factor not only for the enhanced responses of sensitized primary afferents but also for the depressed responses of desensitized primary afferents.

  • 75.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Abbs, J H
    Finger movement responses of cutaneous mechanoreceptors in the dorsal skin of the human hand.1991In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 65, no 3, p. 657-670Article in journal (Refereed)
    Abstract [en]

    1. The movement sensitivity of dorsal skin mechanoreceptors in the human hand was studied by the use of single afferent recording techniques. 2. Units were classified as slowly (SA) and fast adapting (FA) and further characterized by thresholds to vertical indentation and by receptive-field sizes. Whereas SA units were evenly distributed within the supply area of the superficial branch of the radial nerve. FA units were usually situated near joints. 3. The proportion of different receptor types (32% SAI, 32% SAII, 28% FAI, 8% FAII; n = 107) compared favorably with previous electrophysiological and anatomic data, arguing for minimal sampling bias. The majority of the skin mechanoreceptive units were SA, largely due to a relative scarcity of FAII [Pacinian corpuscles (PC)] units. 4. A large majority (92%) of the afferents responded to active hand or finger movements. Responses in all unit types were consistent with observed movement-induced deformations of their receptive fields. 5. FAI units responded bidirectionally, albeit usually with somewhat higher discharge frequencies for finger flexion, which in most cases were associated with skin stretch. FAI units showed meager responses to remote stimuli, typically responding to one or, at the most, two adjacent joints. 6. SA units typically showed simple directional responses to joint movements with an increased discharge during flexion and a reduced discharge during extension. Joint movement that influenced the skin within the receptive field of SA units elicited graded responses even if the field, as assessed by perpendicular indentations, was minute. This finding suggests that definition of cutaneous receptive fields by classical perpendicular indentations may be inappropriate for the receptors in the hairy, nonglabrous skin. 7. The interpretation of the data from these recordings suggests that cutaneous mechanoreceptors in the dorsal skin can provide the CNS with detailed kinematic information, at least for movements of the hand.

  • 76.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ascari, L
    Beccai, L
    Roccella, S
    Cabibihan, J-J
    Carrozza, M C
    Bio-inspired sensorization of a biomechatronic robot hand for the grasp-and-lift task.2008In: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 75, no 6, p. 785-95Article in journal (Refereed)
    Abstract [en]

    It has been concluded from numerous neurophysiological studies that humans rely on detecting discrete mechanical events that occur when grasping, lifting and replacing an object, i.e., during a prototypical manipulation task. Such events represent transitions between phases of the evolving manipulation task such as object contact, lift-off, etc., and appear to provide critical information required for the sequential control of the task as well as for corrections and parameterization of the task. We have sensorized a biomechatronic anthropomorphic hand with the goal to detect such mechanical transients. The developed sensors were designed to specifically provide the information about task-relevant discrete events rather than to mimic their biological counterparts. To accomplish this we have developed (1) a contact sensor that can be applied to the surface of the robotic fingers and that show a sensitivity to indentation and a spatial resolution comparable to that of the human glabrous skin, and (2) a sensitive low-noise three-axial force sensor that was embedded in the robotic fingertips and showed a frequency response covering the range observed in biological tactile sensors. We describe the design and fabrication of these sensors, their sensory properties and show representative recordings from the sensors during grasp-and-lift tasks. We show how the combined use of the two sensors is able to provide information about crucial mechanical events during such tasks. We discuss the importance of the sensorized hand as a test bed for low-level grasp controllers and for the development of functional sensory feedback from prosthetic devices.

  • 77.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Bäckström, P A
    Bäckström, L O
    Single unit retrieval in microneurography: a microprocessor-based device controlled by an operator.1988In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 24, no 2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    A microprocessor-based device was constructed to retrieve single unit activity from nerve recordings contaminated by other units and EMG activity. The microneurographic signal is sampled at 10 kHz and an algorithm applied to identify impulses from a single nerve fibre. On line, a TTL pulse is delivered when an event, i.e. a provisional nerve impulse, is selected. The wave form and clock time of events are stored. Moreover, the latest selected event and the actual selection criteria are continuously displayed on a standard oscilloscope. Off line, the wave form and clock time of events as well as an instantaneous frequency plot can be displayed on the oscilloscope. The final selection of events is done with a combination of a second algorithm, which essentially is a wave form comparator, and a manual check. The device is controlled either by hardware, with knobs on the front panel, or by software through a data bus connected to a microcomputer. Clock times and wave forms of the events, which are stored in the microprocessor memory, may also be presented on the data bus for later off-line analysis and coordination with other related signals collected during the experiment, e.g. transducer and electromyography records, whether these were stored on analog or digital tape or computer disc. Compared to other available techniques, the device has a superior discriminative power when electromyographic artefacts are present.

  • 78.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Essick, G K
    Trulsson, Mats
    Olsson, Kurt Å
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Receptor encoding of moving tactile stimuli in humans. I. Temporal pattern of discharge of individual low-threshold mechanoreceptors.1995In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 15, no 1 Pt 2, p. 830-847Article in journal (Refereed)
    Abstract [en]

    The response of 70 cutaneous, low-threshold mechanoreceptors in the human median, radial and inferior alveolar nerves to well controlled brush stimuli moving across the receptive field was quantitatively studied. Microneurography was used to obtain the response of each to multiple velocities from 0.5 to 32 cm/sec in at least two opposing directions. A high degree of response consistency was observed from the slowly adapting receptors to replication of the same stimulus and to a lesser, but significant degree from the fast adapting receptors. The evoked discharge reflected up to three partially overlapping phases of the moving stimulus: skin compression, indentation, and stretch. Although the overall discharge rate increased with both stimulus velocity and force, the spatial discharge pattern was preserved to a high degrees. In contrast, the discharge patterns differed for opposing and orthogonal directions. Reducing the area of skin surrounding the receptive field that was contacted by the moving stimuli had little effect on the evoked response. Individual mechanoreceptors display highly reliable differences to brush stimuli moving at different velocities. to brush stimuli moving at different velocities. Moreover, different directions of movement evoke differences in the discharge that are consistently observed upon replication of the same stimuli. Despite the richness and consistency in the spatial discharge pattern displayed by individual receptors, it is argued that the details of the patterns are not likely used by the CNS to infer information about direction and velocity of movement across the skin. Rather, the intensity of discharge is proposed as a plausible information-bearing attribute of the stimulus-evoked response.

  • 79.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Howe, Robert
    Westling, Göran
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Cutkosky, Mark
    A Physiological Method for Relaying Frictional Information to a Human Teleoperator1993In: IEEE Transactions on Systems, Man and Cybernetics, ISSN 0018-9472, E-ISSN 2168-2909, Vol. 23, no 2, p. 427-432Article in journal (Refereed)
    Abstract [en]

    The ability to sense and respond to frictional variations is important for dexterous manipulation. It has been demonstrated that humans apply forces to an object on the basis of its anticipated frictional properties. After contact , tactile receptors provide information on the actual frictional properties and ensure that the applied finger tip allow for a safety margin against slips during the ensuing manipulation. With inappropriate forces, incipient and overt slips occur which produce receptor discharges and elicit automatic adjustments of the finger tip forces to increase the safety margins against future slips. It is demonstrated that it is possible to elicit rapid, nonhabituating and sustained grasp responses by means of a tactile display. Subjects grasped and lifted an instrumented test object using the thumb and index finger. While the object was held in air, rapid but small sliding movements were invoked between the object and either contact plate and caused a load force redistribution. This reliably triggered a grasp force increase similar to the ones elicited by natural slips occuring during normal manipulation. An important application of this finding is in relaying frictional information from a slave hand to a human operator. Furthermore, it may make it possible to reduce disparity between master and slave hands in force reflective telemanipulation systems.

  • 80.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Niclas
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Skin strain patterns provide kinaesthetic information to the human central nervous system.1995In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 487, no 1, p. 243-251Article in journal (Refereed)
    Abstract [en]

    1. We investigated the contribution of skin strain-related sensory inputs to movement perception and execution in five normal volunteers. The dorsal and palmar skin of the middle phalanx and the proximal interphalangeal (PIP) joint were manipulated to generate specific strain patterns in the proximal part of the index finger. To mask sensations directly related to this manipulation, skin and deeper tissues were blocked distal to the mid-portion of the proximal phalanx of the index finger by local anaesthesia. 2. Subjects were asked to move their normal right index finger either to mimic any perceived movements of the anaesthetized finger or to touch the tip of the insentient finger. 3. All subjects readily reproduced actual movements induced by the experimenter at the anaesthetized PIP joint. However, all subjects also generated flexion movements when the experimenter did not induce actual movement but produced deformations in the sentient proximal skin that were similar to those observed during actual PIP joint flexion. Likewise, the subjects indicated extension movement at the PIP joint when strain patterns corresponding to extension movements were induced. 4. In contrast, when the skin strain in the proximal part of the index finger was damped by a ring applied just proximal to the PIP joint within the anaesthetized skin area, both tested subjects failed to perceive PIP movements that actually took place.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 81.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Trulsson, Mats
    Neural network analysis of the information content in population responses from human periodontal receptors1992In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 1710, p. 257-266Article in journal (Refereed)
    Abstract [en]

    Understanding of the information processing in some sensory systems is hampered for several reasons. First, some of these systems may depend on several receptor types with different characteristics, and the crucial features of natural stimuli encoded by the receptors are rarely known with certainty. Second, the functional output of sensory processing is often not well defined. The human tooth is endowed with several types of sensory receptors. Among these, the mechanoreceptors located in the periodontal ligaments have been implicated in force encoding during chewing and biting. Individual receptors cannot, however, code unambiguously either the direction or the magnitude of the applied forces. Neuronal responses recorded in single human nerve fibers from periodontal receptors were fed to multi-layered feed-forward networks. The networks were trained with error back-propagation to identify specific features of the force stimuli that evoked the receptor responses. It was demonstrated that population responses in periodontal receptors contain information about both the point of attack and the direction of applied forces. It is concluded that networks may provide a powerful tool to investigate the information content in responses from biological receptor populations. As such, specific hypotheses with respect to information processing may be tested using neural networks also in sensory systems less well understood than, for instance, the visual system.

  • 82.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Vallbo, A B
    Classification of human muscle stretch receptor afferents: a Bayesian approach.1990In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 63, no 6, p. 1314-1322Article in journal (Refereed)
    Abstract [en]

    1. A sample of 124 human muscle afferents originating from the finger extensor muscles were recorded from the radial nerve in the upper arm. A method is described to formalize the classification of units in muscle spindle primary and secondary afferents and Golgi tendon organ afferents on the basis of a few, nonrigorous assumptions. The classification was based on experimental data that largely have been described in a series of previous papers, although some additional data were collected in the present study. 2. The units were subjected to five tests providing identification data: twitch contraction test, ramp-and-hold stretch, small-amplitude sinusoidal stretches superimposed on ramp stretch, stretch sensitization, and isometric contraction/relaxation. From these five tests the following eight response features were extracted: response to maximal isometric twitch contractions, type of stretch sensitization, correlation between discharge rate and contractile force, response to sudden isometric relaxation, presence or absence of an initial burst, deceleration response, prompt silencing at slow muscle shortening, and driving by small-amplitude sinusoidal stretches. 3. A Bayesian decision procedure was adopted to classify the units on the basis of the eight discriminators. As a first step, units were provisionally classified into muscle spindle primary and secondary afferents, and Golgi tendon organ afferents, by intuitively weighting their responses to the identification tests. Prior probabilities were estimated on the basis of the provisional classification. The eight response features were analyzed and tabulated for all afferents, and the likelihood functions of the tests were directly calculated on the basis of these data.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 83.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Vallbo, A B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Dynamic response of human muscle spindle afferents to stretch.1990In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 63, no 6, p. 1297-1306Article in journal (Refereed)
    Abstract [en]

    1. One hundred and twenty-four muscle afferents from the finger extensor muscles were recorded from the radial nerve in human subjects. 2. The afferents were provisionally classified as muscle spindle primary (78/124) and secondary afferents (25/124), and Golgi tendon organ afferents (21/124), on the basis of their response to 1) maximal twitch contractions, 2) 20- and 50-Hz sinusoids superimposed on ramp-and-hold stretches, 3) stretch sensitization, and 4) isometric contractions and sudden relaxations. 3. Ramp-and-hold stretches at two velocities, 10 and 50 degrees/s, were applied to the appropriate metacarpophalangeal (MCP) joint while the parent muscle remained relaxed. For each unit three discrete parameters were assessed: the presence or absence of 1) an initial burst at the commencement of the ramp stretch, 2) a deceleration response at the beginning of the hold phase, and 3) a prompt silencing at muscle shortening. In addition, two kinds of dynamic indexes were calculated for 79 of the muscle spindle afferents. 4. Most spindle afferents responded readily to stretch, whereas the Golgi tendon organ afferents produced very poor stretch responses. All of them lacked a static response, whereas the dynamic response, when present at all, consisted of only a few impulses. 5. The dynamic index was higher for spindle primaries than for secondaries, and this difference was statistically significant although the distribution was unimodal for spindle afferents as a group. Hence, this parameter was a poor discriminator. 6. Initial bursts, deceleration responses, and silences during imposed shortening were more common in spindle primaries than in secondaries. The differences were significant in all these respects. 7. The three discrete parameters were statistically pairwise independent for the spindle afferents, justifying the combination of the three into a useful battery for discrimination between primary and secondary spindle afferents and the use of this battery as a partial data base for a probability approach towards a solid classification of human muscle afferents.

  • 84.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Vallbo, A B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Muscle afferent responses to isometric contractions and relaxations in humans.1990In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 63, no 6, p. 1307-1313Article in journal (Refereed)
    Abstract [en]

    1. One hundred and two single afferents from the finger extensor muscles of humans were studied with the microneurography technique. 2. The afferents were provisionally classified as primary muscle spindle afferents (62/102), secondary spindle afferents (22), and Golgi tendon organ afferents (18) on the basis of their responses to four tests: 1) ramp-and-hold stretch, 2) 20- and 50-Hz small-amplitude sinusoidal stretch superimposed on ramp-and-hold stretch, 3) maximal isometric twitch contraction, and 4) stretch sensitization. 3. The response profiles of the three unit types were analyzed during slowly rising isometric contraction terminating with an abrupt relaxation. About 75% (61/84) of all muscle spindle afferents increased their discharge during isometric contraction, whereas the discharge was reduced for the remaining afferents. All Golgi tendon organs increased their discharge during the contraction. 4. The level of extrafusal contraction at which a spindle afferent increased its discharge rate often varied from trial to trial, speaking against a fixed fusimotor recruitment level of the individual spindle ending. 5. In 70% of the spindle afferents, a distinct burst of impulses appeared when the subject rapidly relaxed after the isometric contraction. The burst was more common and usually much more prominent with primary than secondary afferents, often reaching instantaneous discharge rates well above 100 Hz. 6. Whereas all Golgi tendon organ afferents displayed an increased discharge during the contraction phase, only one of them exhibited a rate acceleration close to the relaxation phase. However, this response could clearly be identified as being of different nature than the spindle bursts.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 85.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Vallbo, A B
    Stretch sensitization of human muscle spindles.1988In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 400, p. 101-11Article in journal (Refereed)
    Abstract [en]

    1. Sixty-seven afferents from the finger extensor muscles were consecutively recorded by microneurography. 2. The units were classified as primary or secondary muscle spindle afferents or Golgi tendon organ afferents on the basis of their responses to ramp-and-hold stretches, sinusoidals superimposed on ramp-and-hold stretches, maximal twitch contractions and isometric contractions and relaxations. 3. The muscle was repeatedly stretched and then either kept short or long for a few seconds followed by a slow ramp stretch. The responses of the muscle afferents to the slow stretch were compared under the two conditions. 4. Thirty out of thirty-eight units classified as primary spindle afferents and four out of eleven units classified as secondary afferents showed an enhanced response to the slow ramp when the muscle had been kept short compared to the response when the muscle had been kept long. 5. None of the eighteen Golgi tendon organ afferents showed any difference in this respect. 6. It is concluded that stretch sensitization does occur in human muscle spindles and, when present, constitutes firm evidence of the afferent originating from a muscle spindle rather than a Golgi tendon organ. In addition, due to differences in the response characteristics of primaries and secondaries, the test may aid in separating muscle spindle primary afferents from secondary afferents.

  • 86.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Vallbo, A B
    Twitch contraction for identification of human muscle afferents.1987In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 131, no 1, p. 129-138Article in journal (Refereed)
    Abstract [en]

    A classical test to differentiate between Golgi tendon organs and muscle spindles is the twitch contraction elicited by electrical stimulation. The possibility of producing maximal twitches in the finger extensor muscles using surface stimulation over the muscle belly was investigated as well as the feasibility of the test in microneurography experiments. Electrical stimuli were applied either over the muscle in the forearm or the radial nerve in the upper arm, while the resulting torque output at single metacarpophalangeal joints was measured. The relationship between current intensity and maximal contraction force was determined and stimulus response plots were constructed over a large range of current intensities. Stimulation of the radial nerve always yielded plots with a steep and monotonous rising limb up to a plateau. It was concluded that the plateau represented maximal twitch contractions. With transcutaneous stimulation over the muscle belly, the stimulus response plots were usually more complex. However, this could be explained by force transmission through the intertendinous connections on the dorsum of the hand and by antagonist activation. It was concluded that maximal twitch contractions can readily be elicited in the human extensor digitorum muscle with nonpainful transcutaneous electrical stimulations. Moreover, maximal twitches are compatible with single unit recording from muscle afferents in microneurography experiments.

  • 87.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Independent control of human finger-tip forces at individual digits during precision lifting.1992In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 450, p. 547-64Article in journal (Refereed)
    Abstract [en]

    1. Subjects lifted an object with two parallel vertical grip surfaces and a low centre of gravity using the precision grip between the tips of the thumb and index finger. The friction between the object and the digits was varied independently at each digit by changing the contact surfaces between lifts. 2. With equal frictional conditions at the two grip surfaces, the finger-tip forces were about equal at the two digits, i.e. similar vertical lifting forces and grip forces were used. With different frictions, the digit touching the most slippery surface exerted less vertical lifting force than the digit in contact with the rougher surface. Thus, the safety margins against slips were similar at the two digits whether they made contact with surfaces of similar or different friction. 3. During digital nerve block, large and variable safety margins were employed, i.e. the finger-tip forces did not reflect the surface conditions. Slips occurred more frequently than under normal conditions (14% of all trials with nerve block, <5% during normal conditions), and they only occasionally elicited compensatory adjustments of the finger-tip forces and then at prolonged latencies. 4. The partitioning of the vertical lifting force between the digits was thus dependent on digital afferent inputs and resulted from active automatic regulation and not just from the mechanics of the task. 5. The safety margin employed at a particular digit was mainly determined by the frictional conditions encountered by the digit, and to a lesser degree by the surface condition at the same digit in the previous lift (anticipatory control), but was barely influenced by the surface condition at the other digit. 6. It was concluded that the finger-tip forces were independently controlled for each digit according to a 'non-slip strategy'. The findings suggest that the force distribution among the digits represents a digit-specific lower-level neural control establishing a stable grasp. This control relies on digit-specific afferent inputs and somatosensory memory information. It is apparently subordinated to a higher-level control that is related to the total vertical lifting and normal forces required by the lifting task and the relevant physical properties of the manipulated object.

  • 88.
    Edin, Benoni
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Beccai, L
    Ascari, L
    Roccella, S
    Cabibihan, J J
    Carrozza, M C
    A Bio-inspired approach for the design and characterization of a tactile sensory system for a cybernetic prosthetic hand2006In: Robotics and Automation: Proceedings of the 2006 IEEE International Conference on Robotics and Automation, ISSN 1050-4729, p. 1354-1358Article in journal (Refereed)
    Abstract [en]

    REcent research in prosthetic hands aims at developing innovative cybernetic systems able to allow users to feel an artificial hand as part of their bodies by providing the tactile sensation of a natural hand. Such prostheses must be endowed with artificial proprioceptive and exteroceptive sensory systems as well as appropriate neural interfaces able to exchange sensorymotor signals between the body and the nervous system of an amputee. Based on consideration of available neurophysiological and behavioral data in humans and on the specific sensory needs to control a prototypical grasp-and-lift task, two kinds of sensors were developed: on-off contact sensor arrays and triaxial force sensors. Both sensor types were characterized and compared with their biological counterparts. Their ability to convey critical information durin a lift task was evaluated with the sensors integrated in a biomechatronic cybernetic hand.

  • 89. Egecioglu, Emil
    et al.
    Jerlhag, Elisabet
    Salome, Nicolas
    Skibicka, Karolina P.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bohlooly-Y, Mohammad
    Andersson, Daniel
    Bjursell, Mikael
    Perrissoud, Daniel
    Engel, Jorgen A.
    Dickson, Suzanne L.
    Ghrelin increases intake of rewarding food in rodents2010In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 15, no 3, p. 304-311Article in journal (Refereed)
    Abstract [en]

    We investigated whether ghrelin action at the level of the ventral tegmental area (VTA), a key node in the mesolimbic reward system, is important for the rewarding and motivational aspects of the consumption of rewarding/palatable food. Mice with a disrupted gene encoding the ghrelin receptor (GHS-R1A) and rats treated peripherally with a GHS-R1A antagonist both show suppressed intake of rewarding food in a free choice (chow/rewarding food) paradigm. Moreover, accumbal dopamine release induced by rewarding food was absent in GHS-R1A knockout mice. Acute bilateral intra-VTA administration of ghrelin increased 1-hour consumption of rewarding food but not standard chow. In comparison with sham rats, VTA-lesioned rats had normal intracerebroventricular ghrelin-induced chow intake, although both intake of and time spent exploring rewarding food was decreased. Finally, the ability of rewarding food to condition a place preference was suppressed by the GHS-R1A antagonist in rats. Our data support the hypothesis that central ghrelin signaling at the level of the VTA is important for the incentive value of rewarding food.

  • 90.
    Ehrsson, H Henrik
    et al.
    Karolinska Institutet.
    Fagergren, Anders
    Karolinska Institutet.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Forssberg, Hans
    Karolinska Institutet.
    Evidence for the involvement of the posterior parietal cortex in coordination of fingertip forces for grasp stability in manipulation2003In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 90, no 5, p. 2978-2986Article in journal (Refereed)
    Abstract [en]

    Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.

  • 91.
    Ekman, Urban
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Functional brain imaging of cognitive status in Parkinson's disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease (PD) is next to Alzheimer’s disease (AD) the second most common neurodegenerative disease. PD has traditionally been characterised as a motor disorder, but more recent research has revealed that cognitive impairments are frequent. Cognitive impairments in executive functions, attention, and working memory with reliance on dopaminergic transmission, are often described as dominating the cognitive profile in early-phase PD. However, although knowledge about the neuropathology that underlies the cognitive impairments in PD has increased, its features are complex and knowledge remains insufficient. Therefore, the aim of the current thesis was to improve the understanding of how task-evoked brain responses relate to cognitive status in patients with PD, with and without mild cognitive impairment (MCI), and to evaluate the predictive value of PD-MCI in respect of prodromal Parkinson’s disease dementia (PDD). This was conducted within the “new Parkinsonism in Umeå” (NYPUM) project, which is a prospective cohort study. Patients with idiopathic PD were included in this thesis, and the patients were examined with a comprehensive neuropsychological battery and with a functional MRI (fMRI) working memory protocol. During scanning, patients conducted a verbal two-back task in which they needed to maintain and actively update relevant information, and the primary outcome measure was blood-oxygen-level-dependent (BOLD) signal. This thesis shows that patients with PD-MCI had significantly lower BOLD signal responses than patients without MCI in frontal (anterior cingulate cortex) and striatal (right caudate) regions (Study I). The altered BOLD response in the right caudate was associated with altered presynaptic dopamine binding. The fronto-striatal alterations persisted across time but without any additional change. However, decreased posterior cortical (right fusiform gyrus) BOLD signal responses were observed in patients with PD-MCI relative to patients without MCI across time (Study II). Finally, PD-MCI at baseline examination is highly predictive for prodromal PDD with a six-fold increased risk. Cognitive tests with a posterior cortical basis, to a greater extent, are predictive for prodromal PDD than tests with a fronto-striatal basis. The observed working memory related alterations in patients with PD-MCI suggest that early cognitive impairments in PD are linked to fronto-striatal dopaminergic dysfunction. The longitudinal development of cognitive impairment in PD reflects additional posterior cortical dysfunction. This might reflect a dual syndrome, with dopamine-depleted fronto-striatal alterations that characterise PD-MCI in general, whereas additional posterior cortical cognitive alterations with a non-dopaminergic basis to a greater extent characterise prodromal PDD. If, and how, the two potential syndromes interact, is still unclear. Thus, this thesis provides information on cognitive neuropathological changes in PD that might contribute to more relevant choices of pharmacotherapy and diagnostic accuracy in respect of PDD. However, additional large-scale longitudinal imaging studies are needed to further clarify the neuropatholgogical features of PD-MCI in respect of prodromal PDD.

  • 92.
    Ekman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Domellöf, Magdalena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Elgh, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lundquist, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment2014In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, article id 207Article in journal (Refereed)
    Abstract [en]

    Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p < 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p < 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes.

  • 93.
    Ekman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. 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. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study2012In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 11, no 8, p. 679-687Article in journal (Refereed)
    Abstract [en]

    Background: Many patients with Parkinson's disease have mild cognitive impairment (MCI). Deficits in executive functions and working memory suggest dysfunctional frontostriatal brain circuitry. We aimed to assess brain responses during a working memory task in a cohort of newly diagnosed drug-naive patients with Parkinson's disease with and without MCI.

    Methods: Participants were recruited within a prospective cohort study of incident patients with idiopathic parkinsonism, including Parkinson's disease. Between Jan 1, 2004, and April 30, 2009, all physicians in the Umea catchment area were requested to refer all individuals with suspected parkinsonism to the Department of Neurology at lima University. Included patients fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease. Control individuals were matched on the basis of age and sex with the first 50 patients included in the study. Participants who scored 1.5 SDs or more below the population mean on at least two cognitive measures were diagnosed with MCI. The primary outcome measures were functional MRI blood-oxygen-level-dependent signal and SPECT presynaptic uptake. Functional MRI was done during a verbal two-back working memory task. Presynaptic dopamine SPECT was done to assess presynaptic striatal dopaminergic system integrity. Event-related transient analyses of functional MRI data were done for the whole brain and for frontostriatal regions of interest, and semi-quantitative SPECT analyses were done for striatal regions of interest.

    Findings: Compared with controls (n=24), patients with Parkinson's disease (n=77) had under-recruitment in an extensive brain network including bilateral striatal and frontal regions (p<0.001). Within the Parkinson's disease group, patients with Parkinson's disease and MCI (n=30) had additional under-recruitment in the right dorsal caudate nucleus (p=0.005) and the bilateral anterior cingulate cortex (p<0.001) compared with patients with Parkinson's disease without MCI (n=26). In patients with Parkinson's disease and MCI, SPECT uptake in the right caudate was lower than in patients with Parkinson's disease without MCI (p=0.008) and correlated with striatal functional MRI blood-oxygen-level-dependent signal (r=0.32, p=0.031).

    Interpretation: These altered brain responses in patients with Parkinson's disease and MCI suggest that cognitive impairment is linked to frontostriatal dysfunction.

  • 94.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bergström, Fredrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Unconscious working memory engages the prefrontal cortex2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no Suppl., p. S74-S74Article in journal (Other academic)
  • 95.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kalpouzos, Grégoria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rewiring the brain with repeated retrieval: A parametric fMRI study of the testing effect2011In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 505, no 1, p. 36-40Article in journal (Refereed)
    Abstract [en]

    The "testing effect" refers to the beneficial effects on memory performance from being tested, a phenomenon of potentially substantial implications in educational settings. While the effect itself is firmly established in previous research, little is known of related brain changes. Here we used fMRI and a parametric design to show that repeated successful retrieval during a memory acquisition phase leads to higher brain activity in the anterior cingulate cortex (ACC) at a subsequent test phase. The extent of ACC activity increase correlated across individuals with memory performance 5 months later. In relation to recent research that associates the ACC with memory consolidation processes, the present results suggest that the testing effect may operate at the systems level by enhancing consolidation of memory representations.

  • 96.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Item-specific training reduces prefrontal cortical involvement in perceptual awareness2008In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 20, no 10, p. 1777-1787Article in journal (Refereed)
    Abstract [en]

    Previous studies on the neural correlates of perceptual awareness implicate sensory-specific regions and higher cortical regions such as the prefrontal cortex (PFC) in this process. The specific role of PFC regions is, however, unknown. PFC activity could be bottom-up driven, integrating signals from sensory regions. Alternatively, PFC regions could serve more active top-down processes that help to define the content of consciousness. To compare these alternative views of PFC function, we used functional magnetic resonance imaging and measured brain activity specifically related to conscious perception of items that varied in ease of identification (by being presented 0, 12, or 60 times previously). A bottom-up account predicts that PFC activity would be largely insensitive to stimulus difficulty, whereas a top-down account predicts reduced PFC activity as identification becomes easier. The results supported the latter prediction by showing reduced activity for previously presented compared to novel items in the PFC and several other regions. This was further confirmed by a functional connectivity analysis showing that the interaction between frontal and visual sensory regions declined as a function of ease of identification. Given the attribution of top-down processing to PFC regions in combination with the marked decline in PFC activity for easy items, these findings challenge the prevailing notion that the PFC is necessary for consciousness.

  • 97.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Details of the construction of perception: a closer look at illusory contours2009In: Frontiers in neuroscience, ISSN 1662-453X, Vol. 3, no 2, p. 159-160Article in journal (Refereed)
  • 98.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Stiernstedt, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Öhlund, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    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).
    Changing Zaire to Congo: The fate of no-longer relevant mnemonic information.2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 101, p. 1-7Article in journal (Refereed)
    Abstract [en]

    In an ever-changing world there is constant pressure on revising long-term memory, such when people or countries change name. What happens to the old, pre-existing information? One possibility is that old associations gradually are weakened and eventually lost. Alternatively, old and no longer relevant information may still be an integral part of memory traces. To test the hypothesis that old mnemonic information still becomes activated when people correctly retrieve new, currently relevant information, brain activity was measured with fMRI while participants performed a cued-retrieval task. Paired associates (symbol-sound and symbol-face pairs) were first learned during two days. Half of the associations were then updated during the next two days, followed by fMRI scanning on day 5 and also 18months later. As expected, retrieval reactivated sensory cortex related to the most recently learned association (visual cortex for symbol-face pairs, auditory cortex for symbol-sound pairs). Critically, retrieval also reactivated sensory cortex related to the no-longer relevant associate. Eighteen months later, only non-updated symbol-face associations were intact. Intriguingly, a subset of the updated associations was now treated as though the original association had taken over, in that memory performance was significantly worse than chance and that activity in sensory cortex for the original but not the updated associate correlated (negatively) with performance. Moreover, the degree of "residual" reactivation during day 5 inversely predicted memory performance 18months later. Thus, updating of long-term memory involves adding new information to already existing networks, in which old information can stay resilient for a long time.

  • 99. Essick, G K
    et al.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Receptor encoding of moving tactile stimuli in humans. II. The mean response of individual low-threshold mechanoreceptors to motion across the receptive field.1995In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 15, no 1, p. 848-864Article in journal (Refereed)
    Abstract [en]

    The mean firing rate evoked in 70 cutaneous, low-threshold mechanoreceptors in the human median, radial, and inferior alveolar nerves by stimulus motion across the skin was quantitatively studied. Moving stimuli, controlled for velocity, direction, and length of skin traversed, were provided by a servo-controlled motor that carried a brush across the receptive field. Each unit was studied with stimuli delivered at multiple velocities from 0.5 to 32 cm/sec in at least two opposing directions. A power function provided an excellent description of the MFR-versus-velocity relationship. The exponent n was interpreted to reflect the receptor's sensitivity to changes in stimulus velocity, and the multiplicative constant c, the predicted response to stimuli moving at 1.0 cm/sec. The fast adapting mechanoreceptors exhibited higher sensitivity to stimulus velocity than the slowly adapting mechanoreceptors. The mean velocity at which the fast adapting units were predicted to first respond to movement was also higher. Estimates of n, c, or both differed significantly for stimuli delivered in opposing directions for more than 70% of the mechanoreceptors. No direction of motion consistently led to power function parameters with higher values so as to suggest a "preferred" regional direction of motion for the entire population. Neither the directional difference in n nor c could be attributed to directional differences in the forces applied across the receptive fields. These findings suggest that information about velocity and direction is represented in the mean firing rate responses evoked in the population of mechanoreceptors activated by a moving tactile stimulus.

  • 100.
    Fernandes, Carla Patricia Duarte
    et al.
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Westlye, Lars Tjelta
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Giddaluru, Sudheer
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Christoforou, Andrea
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University and Stockholm Brain Institute, Uppsala, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Lundervold, Astri Johansen
    Department of Biological and Medical Psychology, K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital.
    Reinvang, Ivar
    Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Steen, Vidar Martin
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Le Hellard, Stéphanie
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Espeseth, Thomas
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations2014In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 222, no 1-2, p. 60-66Article in journal (Refereed)
    Abstract [en]

    The rs1344706 single nucleotide polymorphism within intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuroimaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomical atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.

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