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  • 251.
    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.

  • 252.
    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.

  • 253.
    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.

  • 254.
    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.

  • 255.
    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.

  • 256.
    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)

  • 257.
    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.

  • 258.
    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)

  • 259.
    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.

  • 260.
    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)

  • 261.
    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.

  • 262.
    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.

  • 263.
    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.

  • 264.
    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.

  • 265.
    Edin, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikberg, Maria L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlin, Anna M.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The Distribution of Macrophages with a M1 or M2 Phenotype in Relation to Prognosis and the Molecular Characteristics of Colorectal Cancer2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, p. e47045-Article in journal (Refereed)
    Abstract [en]

    High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC). Tumor associated macrophages (TAMs) play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI) screening status and the CpG island methylator phenotype (CIMP). A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2) (also denoted iNOS) as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+)) or M2 (CD163(+)) phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+) and CD163(+) cells (P<0.0001). A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001) and CD163 (P<0.0001) infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2+ cells had a significantly better prognosis than those infiltrated by few NOS2+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.

  • 266.
    Edin, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikberg, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Macrophages: Good guys in colorectal cancer2013In: Oncoimmunology, ISSN 2162-4011, Vol. 2, no 2, p. e23038-Article in journal (Refereed)
    Abstract [en]

    Macrophages play a complex role in tumor progression since they can exert both tumor-preventing (M1 macrophages) and tumor-promoting (M2 macrophages) activities. In colorectal carcinoma (CRC), at odds to many other cancers, macrophage infiltration has been correlated with an improved patient survival. In a recent study, we have evaluated the distribution of M1 and M2 macrophage subtypes in CRC and their impact on patient prognosis.

  • 267.
    Edin, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikberg, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Phenotypic skewing of macrophages in vitro by secreted factors from colorectal cancer cells2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e74982-Article in journal (Refereed)
    Abstract [en]

    Macrophages are cells with many important functions in both innate and adaptive immune responses and have been shown to play a complex role in tumor progression since they harbour both tumor preventing (M1 macrophages) and tumor promoting (M2 macrophages) activities. In many human cancers, infiltrating macrophages have been associated with a poor patient prognosis, and therefore suggested to be mainly of an M2 phenotype. However, we and others have previously shown that increased macrophage density in colorectal cancer (CRC) instead is correlated with an improved prognosis. It is an intriguing question if the different roles played by macrophages in various cancers could be explained by variations in the balance between M1 and M2 macrophage attributes, driven by tumor- or organ-specific factors in the tumor microenvironment of individual cancers. Here, we utilized an in vitro cell culture system of macrophage differentiation to compare differences and similarities in the phenotype (morphology, antigen-presentation, migration, endocytosis, and expression of cytokine and chemokine genes) between M1/M2 and tumor activated macrophages (TAMs), that could explain the positive role of macrophages in CRC. We found that secreted factors from CRC cells induced TAMs of a "mixed" M1/M2 phenotype, which in turn could contribute to a "good inflammatory response". This suggests that re-education of macrophages might allow for important therapeutic advances in the treatment of human cancer.

  • 268.
    Edman, Anne-Christine
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Myofibrillens finstruktur i tvärstrimmig skelettmuskulatur1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The detailed structure of the myofibrillar material in fibres from different muscles has been studied. Specimens have been obtained from human muscles and from different muscles frequently examined in experimental studies. Both light- and electron microscopical techniques have been used. Of central importance has been the method, which makes it possible to prepare ultrathin sections of frozen tissue, i.e. cryo-ult- ramicrotomy. A number of techniques for image analysis have been applied in order to obtain objektive data from the micrographs.

    In Paper I the present knowledge about muscle fibre structure, cryo-- sectioning and image analysis is summarized and relevant methodological problems are discussed. Paper II describes the detailed structure of the C-zone of the A-band and shows, above all, that structures occur with different repeats along the long axis of the myofibril. Paper III describes the subcellular organization of different fibres in a homogeneous (based on enzyme histochemical mATPase) population, and shows that different structural characteristies can vary independently of each other. Paper IV describes the structural diversity of the myofibrillar M-band, and paper V the diversity of the myofilament fine structure in different fibres. The results show that there is a most sophisticated, and previosly unrealized, structural specialization both within the myofibrils and between myofibrils from different fibres and muscles, even if the fibres are of the same fibre type. The findings suggest that generally used models, showing the structural organization within myofibrils and myofilaments, are oversimplifications. The fibre population is more heterogeneously built up than the common systems for fibre type classification makes one to belive.

  • 269.
    Edmundsson, David S.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Toolanen, Goran L.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Muscle changes in patients with diabetes and chronic exertional compartment syndrome before and after treatment with fasciotomy2018In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 57, no 2, p. 229-239Article in journal (Refereed)
    Abstract [en]

    Introduction: Muscle changes in patients with diabetes and lower leg pain due to chronic exertional compartment syndrome (CECS) were investigated before and after fasciotomy. Methods: The tibialis anterior muscle was analyzed with histochemical and morphological techniques in 7 patients with diabetes and CECS before fasciotomy and in 5 of them 1 year after fasciotomy. Nondiabetic patients with CECS and healthy participants served as references. Results: Before treatment, walking distance until occurrence of pain was limited (<0.2 km). Intramuscular pressure was significantly higher than in reference participants. Muscle analysis showed changes pathognomonic for neuropathy and myopathy and a restricted capillary network, with significantly more severe changes in the muscles of patients with diabetes than in the muscles of nondiabetic patients. Treatment with fasciotomy improved clinical signs, increased walking ability, and reduced muscle abnormalities, but muscle capillarization remained low. Discussion: Patients with diabetes and CECS have distinct pathological changes in affected muscles. Pressure-relieving fasciotomy triggers a regenerative response in the muscle tissue but not in the capillary bed.

  • 270.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Muscle changes in diabetics with chronic compartment syndromeManuscript (preprint) (Other academic)
  • 271.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Evidence for low muscle capillary supply as a pathogenic factor in chronic compartment syndrome2010In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 20, no 6, p. 805-813Article in journal (Refereed)
    Abstract [en]

    There is a paucity of data regarding the pathogenesis of chronic exertional compartment syndrome (CECS), its consequences for the muscles and the effects of treatment with fasciotomy. We analyzed biopsies from the tibialis anterior muscle, from nine patients, obtained during a decompressing fasciotomy and during follow-up 1 year later. Control biopsies were obtained from nine normal subjects. Muscle capillarity, fiber-type composition and fiber area were analyzed with enzyme- and immunohistochemistry and morphometry. At baseline, CECS patients had lower capillary density (273 vs 378 capillaries/mm(2), P=0.008), lower number of capillaries around muscle fibers (4.5 vs 5.7, P=0.004) and lower number of capillaries in relation to the muscle fiber area (1.1 vs 1.5, P=0.01) compared with normal controls. The fiber-type composition and fiber area did not differ, but focal signs of neuromuscular damage were observed in the CECS samples. At 1-year follow-up after fasciotomy, the fiber area and the number of fibers containing developmental myosin heavy chains were increased, but no enhancement of the capillary network was detected. Thus, morphologically, patients with CECS seemed to have reduced microcirculation capacity. Fasciotomy appeared to trigger a regenerative response in the muscle, however, without any increase in the capillary bed.

  • 272. 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.

  • 273.
    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.

  • 274. Ekblom, B
    et al.
    Ekblom, O
    Malm, Christer
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Infectious episodes before and after a marathon race.2006In: Scandinavian Journal of Medicine & Science in Sports, ISSN 0905-7188, Vol. 16, no 4, p. 287-93Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the incidence of self-reported infectious episodes (IE) during 3 weeks before (pre-IE) and 3 weeks after (post-IE) a marathon race and relate these figures to training status, running time, socioeconomic and demographic factors. Two questionnaires, including questions about important factors for IE incidence, were given to a representative cohort of 1694 runners (17% of all finishers) in the Stockholm Marathon 2000. Pre-IE incidence in the cohort was 17% with no difference between women and men. Post-IE incidence in the whole cohort was 19% with no significant (P>0.05) difference between women and men. The post-IE incidence in runners without a pre-IE was 16% (P>0.05 to pre-IE incidence). In the group of runners with pre-IE, 33% experienced an IE after the race also (P<0.05 to Pre-IE incidence). A logistic regression analysis showed that younger age and pre race health status and, for men only, experienced nausea during and after the race were depended factors explaining post-IE incidence. Younger runners were more prone to experience IE both before and after the race. There was no relation between training volume 6 months before the race, finishing time and socioeconomic and demographic factors and pre-IE or post-IE. This study does not support the theory of increased infection rate after exhaustive long-distance running ("The Open Window Theory") in recreational runners, but suggests that the sometimes experienced increased rate of infections among athletes can be caused by strenuous exercise too soon after an infection.

  • 275.
    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.

  • 276.
    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.

  • 277.
    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.

  • 278.
    Ekman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Fordell, Helena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Increase of frontal neuronal activity in chronic neglect after training in virtual reality2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 284-292Article in journal (Refereed)
    Abstract [en]

    Objectives: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt((R)). Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posners Cuing Task (attention task) after RehAtt((R)) intervention, in patients with chronic neglect.

    Methods: Twelve patients (mean age=72.7years, SD=6.1) with chronic neglect (persistent symptoms >6months) performed the interventions 3 times/wk during 5weeks, in total 15hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posners cuing task before and after the intervention.

    Results: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations.

    Conclusions: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt((R)) in chronic neglect.

  • 279.
    El-Habta, Roine
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Chen, Jialin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pingel, Jessica
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Tendinosis-like changes in denervated rat Achilles tendon2018In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 19, article id 426Article in journal (Refereed)
    Abstract [en]

    Background: Tendon disorders are common and lead to significant disability and pain. Our knowledge of the ‘tennis elbow’, the ‘jumpers knee’, and Achilles tendinosis has increased over the years, but changes in denervated tendons is yet to be described in detail. The aim of the present study was to investigate the morphological and biochemical changes in tendon tissue following two weeks of denervation using a unilateral sciatic nerve transection model in rat Achilles tendons.

    Methods: Tendons were compared with respect to cell number, nuclear roundness, and fiber structure. The non-denervated contralateral tendon served as a control. Also, the expression of neuromodulators such as substance P and its preferred receptor neurokinin-1 receptor, NK-1R, was evaluated using real-time qRT-PCR.

    Results: Our results showed that denervated tendons expressed morphological changes such as hypercellularity; disfigured cells; disorganization of the collagen network; increased production of type III collagen; and increased expression of NK-1R.

    Conclusion: Taken together these data provide new insights into the histopathology of denervated tendons showing that denervation causes somewhat similar changes in the Achilles tendon as does tendinosis in rats.

  • 280.
    El-Habta, Roine
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Adipose stem cells enhance myoblast proliferation via acetylcholine and extracellular signal-regulated kinase 1/2 signaling2018In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 57, no 2, p. 305-311Article in journal (Refereed)
    Abstract [en]

    Introduction: In this study we investigated the interaction between adipose tissue-derived stem cells (ASCs) and myoblasts in co-culture experiments. Methods: Specific inductive media were used to differentiate ASCs in vitro into a Schwann cell-like phenotype (differentiated adipose tissuederived stem cells, or dASCs) and, subsequently, the expression of acetylcholine (ACh)-related machinery was determined. In addition, the expression of muscarinic ACh receptors was examined in denervated rat gastrocnemius muscles. Results: In contrast to undifferentiated ASCs, dASCs expressed more choline acetyltransferase and vesicular acetylcholine transporter. When co-cultured with myoblasts, dASCs enhanced the proliferation rate, as did ACh administration alone. Western blotting and pharmacological inhibitor studies showed that phosphorylated extracellular signal-regulated kinase 1/2 signaling mediated these effects. In addition, denervated muscle showed higher expression of muscarinic ACh receptors than control muscle. Discussion: Our findings suggest that dASCs promote proliferation of myoblasts through paracrine secretion of ACh, which could explain some of their regenerative capacity in vivo.

  • 281.
    El-Habta, Roine
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Sloniecka, Marta
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, L. J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    The adipose tissue stromal vascular fraction secretome enhances the proliferation but inhibits the differentiation of myoblasts2018In: Stem Cell Research & Therapy, E-ISSN 1757-6512, Vol. 9, article id 352Article in journal (Refereed)
    Abstract [en]

    Background: Adipose tissue is an excellent source for isolation of stem cells for treating various clinical conditions including injuries to the neuromuscular system. Many previous studies have focused on differentiating these adipose stem cells (ASCs) towards a Schwann cell-like phenotype (dASCs), which can enhance axon regeneration and reduce muscle atrophy. However, the stromal vascular fraction (SVF), from which the ASCs are derived, also exerts broad regenerative potential and might provide a faster route to clinical translation of the cell therapies for treatment of neuromuscular disorders.

    Methods: The aim of this study was to establish the effects of SVF cells on the proliferation and differentiation of myoblasts using indirect co-culture experiments. A Growth Factor PCR Array was used to compare the secretomes of SVF and dASCs, and the downstream signaling pathways were investigated.

    Results: SVF cells, unlike culture-expanded dASCs, expressed and secreted hepatocyte growth factor (HGF) at concentrations sufficient to enhance the proliferation of myoblasts. Pharmacological inhibitor studies revealed that the signal is mediated via ERK1/2 phosphorylation and that the effect is significantly reduced by the addition of 100 pM Norleual, a specific HGF inhibitor. When myoblasts were differentiated into multinucleated myotubes, the SVF cells reduced the expression levels of fast-type myosin heavy chain (MyHC2) suggesting an inhibition of the differentiation process.

    Conclusions: In summary, this study shows the importance of HGF as a mediator of the SVF effects on myoblasts and provides further evidence for the importance of the secretome in cell therapy and regenerative medicine applications.

  • 282.
    Elmi, Adrian
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Idahl, Lars-Åke
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Sehlin, Janove
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Modulation of islet ATP content by inhibition or stimulation of the Na(+)/K(+) pump2001In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 426, no 1-2, p. 139-143Article in journal (Refereed)
    Abstract [en]

    High (30 mM) K(+), known to cause beta-cell membrane depolarisation, significantly decreased the islet total ATP content, supporting the view that beta-cell membrane depolarisation can activate the ATP-consuming Na(+)/K(+) pump. Ouabain (1 mM) did not change the islet ATP content after 5-15 min of incubation in the absence or presence of 3 mM glucose but reduced it after 30 min, and in the presence of 20 mM glucose, the reduction by ouabain occurred already after 15 min. Incubation of islets with ouabain for 60 min decreased the islet ATP content in the presence of 3, 10 or 20 mM glucose or 30 mM K(+). Also, the islet glucose oxidation rate was decreased by ouabain. When K(+) deficiency was used to inhibit the Na(+)/K(+) pump, no change in ATP content was observed irrespective of glucose concentration, although K(+) deficiency caused a slight inhibition of the glucose oxidation rate. Diazoxide reduced the islet glucose oxidation rate and increased the islet ATP content in the presence of 20 mM glucose. There may exist a feedback mechanism decreasing the flow of glucose metabolism in response to reduced ATP consumption by the Na(+)/K(+) pump.

  • 283.
    Engels, Patricia E.
    et al.
    University Hospital Basel.
    Tremp, Mathias
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    di Summa, Pietro G.
    Largo, Rene D.
    Schaefer, Dirk J.
    Kalbermatten, Daniel F
    Harvest site influences the growth properties of adipose derived stem cells2013In: Cytotechnology (Dordrecht), ISSN 0920-9069, E-ISSN 1573-0778, Vol. 65, no 3, p. 437-445Article in journal (Refereed)
    Abstract [en]

    The therapeutic potential of adult stem cells may become a relevant option in clinical care in the future. In hand and plastic surgery, cell therapy might be used to enhance nerve regeneration and help surgeons and clinicians to repair debilitating nerve injuries. Adipose-derived stem cells (ASCs) are found in abundant quantities and can be harvested with a low morbidity. In order to define the optimal fat harvest location and detect any potential differences in ASC proliferation properties, we compared biopsies from different anatomical sites (inguinal, flank, pericardiac, omentum, neck) in Sprague-Dawley rats. ASCs were expanded from each biopsy and a proliferation assay using different mitogenic factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) was performed. Our results show that when compared with the pericardiac region, cells isolated from the inguinal, flank, omental and neck regions grow significantly better in growth medium alone. bFGF significantly enhanced the growth rate of ASCs isolated from all regions except the omentum. PDGF had minimal effect on ASC proliferation rate but increases the growth of ASCs from the neck region. Analysis of all the data suggests that ASCs from the neck region may be the ideal stem cell sources for tissue engineering approaches for the regeneration of nervous tissue.

  • 284.
    Englezou, Pavlos C.
    et al.
    University of Manchester.
    Degli Esposti, Mauro
    University of Manchester.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Reid, Adam J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. University of Manchester.
    Terenghi, Giorgio
    University of Manchester.
    Mitochondrial involvement in sensory neuronal cell death and survival2012In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 221, no 4, p. 357-367Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries (PNI) are continuing to be an ever-growing socio-economic burden affecting mainly the young working population and the current clinical treatments to PNI provide a poor clinical outcome involving significant loss of sensation. Thus, our understanding of the underlying factors responsible for the extensive loss of the sensory cutaneous subpopulation in the dorsal root ganglia (DRG) that occurs following injury needs to be improved. The current investigations focus in identifying visual cues of mitochondria-related apoptotic events in the various subpopulations of sensory cutaneous neurons. Sensory neuronal subpopulations were identified using FastBlue retrograde labelling following axotomy. Specialised fluorogenic probes, MitoTracker Red and MitoTracker Orange, were employed to visualise the dynamic changes of the mitochondrial population of neurons. The results reveal a fragmented mitochondrial network in sural neurons following apoptosis, whereas a fused elongated mitochondrial population is present in sensory proprioceptive muscle neurons following tibial axotomy. We also demonstrate the neuroprotective properties of NAC and ALCAR therapy in vitro. The dynamic mitochondrial network breaks down following oxidative exposure to hydrogen peroxide (H2O2), but reinitiates fusion after NAC and ALCAR therapy. In conclusion, this study provides both qualitative and quantitative evidence of the susceptibility of sensory cutaneous sub-population in apoptosis and of the neuroprotective effects of NAC and ALCAR treatment on H2O2-challenged neurons.

  • 285.
    Erba, P
    et al.
    University of Manchester, University Hospital of Basel.
    Mantovani, Cristina
    University of Manchester.
    Kalbermatten, Daniel F
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pierer, G
    University Hospital of Basel.
    Terenghi, Giorgio
    University of Manchester.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Regeneration potential and survival of transplanted undifferentiated adipose tissue-derived stem cells in peripheral nerve conduits2010In: Journal of plastic, reconstructive & aesthetic surgery : JPRAS, ISSN 1878-0539, Vol. 63, no 12, p. e811-e817Article in journal (Refereed)
    Abstract [en]

    Adipose tissue-derived stem cells (ADSCs) have shown potential for the treatment of nerve injuries. Most previous efforts have aimed at stimulating regeneration by using neural-differentiation protocols, but the potential of undifferentiated ADSCs to enhance axonal growth as well as their ability to transdifferentiate in situ have been poorly investigated. In this study, using a rat sciatic nerve model we show that ADSCs, transplanted in an artificial nerve conduit, stimulate axonal outgrowth from the proximal nerve stump and evoke greater Schwann cell (SC) proliferation/intrusion in the distal stump. To track the fate of the transplanted cells, we used green fluorescent protein (GFP)-labelling and polymerase chain reaction (PCR) for the detection of the sex determining region Y (SRY) gene in the donor male cells. Both methods indicated a lack of significant quantities of viable cells 14 days after transplantation. These results suggest that any regenerative effect of transplanted ADSCs is more likely to be mediated by an initial boost of released growth factors and/or by an indirect effect on endogenous SCs activity. Future studies need to address long-term cell survival in tissue-engineered nerve conduits to improve the neuroregenerative potential of ADSCs.

  • 286.
    Erba, Paolo
    et al.
    University Hospitals of Basel and Lausanne.
    Terenghi, Giorgio
    University of Manchester.
    Kingham, Paul J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Neural differentiation and therapeutic potential of adipose tissue derived stem cells2010In: Current stem cell research & therapy, ISSN 1574-888X, Vol. 5, no 2, p. 153-160Article, review/survey (Refereed)
    Abstract [en]

    Neural tissue has historically been regarded as having poor regenerative capacity but recent advances in the growing fields of tissue engineering and regenerative medicine have opened new hopes for the treatment of nerve injuries and neurodegenerative disorders. Adipose tissue has been shown to contain a large quantity of adult stem cells (ASC). These cells can be easily harvested with low associated morbidity and because of their potential to differentiate into multiple cell types, their use has been suggested for a wide variety of therapeutic applications. In this review we examine the evidence indicating that ASC can stimulate nerve regeneration by both undergoing neural differentiation and through the release of a range of growth factors. We also discuss some of the issues that need to be addressed before ASC can be developed as an effective cellular therapy for the treatment of neural tissue disorders.

  • 287.
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Intermediate-sized (skeletin) filaments of heart Purkinje fibres: an investigation into their morphology, composition and function1979Doctoral thesis, comprehensive summary (Other academic)
  • 288.
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    Strenght training and anabolic steroids: a comparative study of the trapezius, a shoulder muscle and the vastus lateralis, a thigh muscle, of strength trained athletes2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Strength training is widely used to increase performance in sports with high physical demands. The use of drugs such as anabolic steroids among athletes is a wellknown phenomenon, and the effects of these drugs on physical performance documented.

    The studies presented in this thesis focused on the mechanisms of muscle fiber hypertrophy in the vastus lateralis and the trapezius muscles of strength trained elite athletes. The main hypothesis was that the muscle adaptations to strength training and anabolic steroids are muscle specific.

    Biopsies were obtained from the trapezius and the vastus lateralis from three groups of elite power lifters. Nine used drugs, ten did not and seven had previously used drugs. Six sedentary males served as controls. The biopsies were frozen and cut in serial cross sections. Histological and immunohistochemical staining techniques were used to analyze muscle fiber morphology and pathology. Fiber type distribution, fiber area, myonuclei number and distribution, satellite cell number and proportion of split fibers were counted and compared for the two muscles within and between the groups.

    The main findings were that: a) Muscle fiber hypertrophy by strength training is further increased by anabolic steroids. b) The number of nuclei per muscle fiber is higher in power lifters using anabolic steroids compared to non-steroids using lifters. c) Among power lifters who have withdrawn from anabolic steroid usage and training for several years, the number of myonuclei, both subsarcolemmal and internal, remains high. d) In active power lifters, anabolic steroids have no further effect on the number of satellite cells per fiber. e) Power lifters have a high proportion of split fibers.

    High intensity resistance training increases muscle strength and banned substances such as testosterone and anabolic steroids can enhance the training effects. The studies on muscle cell morphology presented in this thesis reveals that anabolic steroids and testosterone increases muscle fiber size and adds more nuclei to the muscle cell.

    Based on the morphological appearance of muscle sections from doped and nondoped power lifters, we conclude that testosterone and anabolic steroids enhances the hypertrophic effects of training without adding new features. The addition of myonuclei by training and doping appears to be longer lasting in some muscles than in others. The high proportion of split fibers in power lifter is probably due to high mechanical stress. The findings and conclusions in this thesis raise questions regarding relevant suspension times for athletes caught with banned substances in the body.

  • 289.
    Eriksson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kadi, F
    Tabatabai, P
    Bonnerud, P
    Thornell, L-E
    Anabolic steroids withdrawal in strength trained athletes: how does it affect skeletal musclesManuscript (Other academic)
  • 290.
    Eriksson, Anders
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Kadi, Fawzi
    Malm, Christer
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Skeletal muscle morphology in power-lifters with and without anabolic steroids.2005In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 124, no 2, p. 167-175Article in journal (Refereed)
    Abstract [en]

    The morphological appearance of the vastus lateralis (VL) muscle from high-level power-lifters on long-term anabolic steroid supplementation (PAS) and power-lifters never taking anabolic steroids (P) was compared. The effects of long- and short-term supplementation were compared. Enzyme-immunohistochemical investigations were performed to assess muscle fiber type composition, fiber area, number of myonuclei per fiber, internal myonuclei, myonuclear domains and proportion of satellite cells. The PAS group had larger type I, IIA, IIAB and IIC fiber areas (p<0.05). The number of myonuclei/fiber and the proportion of central nuclei were significantly higher in the PAS group (p<0.05). Similar results were seen in the trapezius muscle (T) but additionally, in T the proportion of fibers expressing developmental myosin isoforms was higher in the PAS group compared to the P group. Further, in VL, the PAS group had significantly larger nuclear domains in fibers containing > or = 5 myonuclei. The results of AS on VL morphology in this study were similar to previously reported short-term effects of AS on VL. The initial effects from AS appear to be maintained for several years.

  • 291.
    Eriksson, Anders
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Hypertrophic muscle fibers with fissures in power-lifters; fiber splitting or defect regeneration?2006In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 126, no 4, p. 409-417Article in journal (Refereed)
    Abstract [en]

    Power-lifters have hypertrophic muscle fibers with fissures seen in cross-sections, called as fiber splitting.Whether this phenomenon is due to real splitting or defective regeneration has not been settled. To elucidate this matter,we have examined biopsies from the trapezius and vastus lateralis of power lifters (P group) and power lifters self-administrating anabolic steroids (PAS group). For this purpose, immunohistochemical staining of serial cross -sections was used. The PAS group had significantly more fibers with fissures than the P group in the vastus lateralis (1.2%+/-0.95% vs 0.35+/-0.34, P < 0.05) but not in the trapezius muscle (1.7% in both groups). Serial sections revealed that the fibers with fissures changed their profile profoundly over short distances. Some such fibers had a mature staining profile, whereas other fibers indicated recent degeneration and/or regeneration. Activation of satellite cells and formation of aberrant segments were also evident. We conclude that the so-called split fibers are due to defect regeneration. Some fibers with fissures are the results of old events of segmental muscle fiber damage, whereas the others reflect an ongoing process. The normal regenerative process is most likely disturbed in power-lifters by their continuous training with repeated high mechanical stress on the muscles.

  • 292.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Activity in part of the neural correlates of consciousness reflects integration2017In: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 55, p. 26-34Article in journal (Refereed)
    Abstract [en]

    Integration is commonly viewed as a key process for generating conscious experiences. Accordingly, there should be increased activity within the neural correlates of consciousness when demands on integration increase. We used fMRI and "informational masking" to isolate the neural correlates of consciousness and measured how the associated brain activity changed as a function of required integration. Integration was manipulated by comparing the experience of hearing simple reoccurring tones to hearing harmonic tone triplets. The neural correlates of auditory consciousness included superior temporal gyrus, lateral and medial frontal regions, cerebellum, and also parietal cortex. Critically, only activity in left parietal cortex increased significantly as a function of increasing demands on integration. We conclude that integration can explain part of the neural activity associated with the generation conscious experiences, but that much of associated brain activity apparently reflects other processes.

  • 293.
    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)
  • 294.
    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.

  • 295.
    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.

  • 296.
    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)
  • 297.
    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.

  • 298.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Vogel, Edward K.
    Lansner, Anders
    Bergström, Fredrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). 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). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Neurocognitive Architecture of Working Memory2015In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 88, no 1, p. 33-46Article, review/survey (Refereed)
    Abstract [en]

    A crucial role for working memory in temporary information processing and guidance of complex behavior has been recognized for many decades. There is emerging consensus that working-memory maintenance results from the interactions among long-term memory representations and basic processes, including attention, that are instantiated as reentrant loops between frontal and posterior cortical areas, as well as sub-cortical structures. The nature of such interactions can account for capacity limitations, lifespan changes, and restricted transfer after working-memory training. Recent data and models indicate that working memory may also be based on synaptic plasticity and that working memory can operate on non-consciously perceived information.

  • 299. 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.

  • 300.
    Faergemann, Erik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Magnetic Resonance Imaging (MRI) to Study Striatal IronAccumulation in a Rat Model of Parkinson’s Disease2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
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