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| 2. |
- Johansson, Veronica, et al.
(författare)
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Beyond Blind Optimism and Unfounded Fears : Deep Brain Stimulation for Treatment Resistant Depression
- 2013
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Ingår i: Neuroethics. - : Springer Science and Business Media LLC. - 1874-5504 .- 1874-5490. ; 6:3, s. 457-471
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of new medical treatments based on invasive technologies has often been surrounded by both hopes and fears. Hope, since a new intervention can create new opportunities either in terms of providing a cure for the disease or impairment at hand; or as alleviation of symptoms. Fear, since an invasive treatment involving implanting a medical device can result in unknown complications such as hardware failure and undesirable medical consequences. However, hopes and fears may also arise due to the cultural embeddedness of technology, where a therapy due to ethical, social, political and religious concerns could be perceived as either a blessing or a threat. While Deep Brain Stimulation (DBS) for treatment resistant depression (TRD) is still in its cradle, it is important to be proactive and try to scrutinize both surfacing hopes and fears. Patients will not benefit if a promising treatment is banned or avoided due to unfounded fears, nor will they benefit if DBS is used without scrutinizing the arguments which call for caution. Hence blind optimism is equally troublesome. We suggest that specificity, both in terms of a detailed account of relevant scientific concerns as well as ethical considerations, could be a way to analyse expressed concerns regarding DBS for TRD. This approach is particularly fruitful when applied to hopes and fears evoked by DBS for TRD, since it can reveal if our comprehension of DBS for TRD suffer from various biases which may remain unnoticed at first glance. We suggest that such biases exist, albeit a further analysis is needed to explore this issue in full.
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| 3. |
- Levinsson, Anders, et al.
(författare)
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Spinal sensorimotor transformation: Relation between cutaneous somatotopy and a reflex network
- 2002
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 22:18, s. 8170-8182
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Tidskriftsartikel (refereegranskat)abstract
- The projection of primary afferents onto spinal interneurons constitutes the first step in sensorimotor transformations performed by spinal reflex systems. Despite extensive studies on spinal somatotopy, uncertainties remain concerning the extent and significance of representational overlap and relation to spinal reflex circuits. To address these issues, the cutaneous projection from the hindpaw and its relation to the topography of lamina V neurons encoding withdrawal reflex strength ("reflex encoders") was studied in rats. Thin and coarse primary afferent terminations in laminas II and III-IV, respectively, were mapped by wheat germ agglutinin-horseradish peroxidase and choleragenoid tracing. The functional weights of these projections were characterized by mapping nociceptive and tactile field potentials and compared with the topography of reflex encoders. Both anatomical and physiological data indicate that thin and coarse skin afferent input is spatially congruent in the horizontal plane. The representation of the hindpaw in the spinal cord was found to be intricate, with a high degree of convergence between the projections from different skin sites. "Somatotopic disruptions" such as the representation of central pads medial to that of the digits were common. The weight distribution of the cutaneous convergence patterns in laminas III-IV was similar to that of lamina V reflex encoders. This suggests that the cutaneous convergence and features such as somatotopic disruptions have specific relations to the sensorimotor transformations performed by reflex interneurons in the deep dorsal horn. Hence, the spinal somatotopic map may be better understood in light of the topography of such reflex systems.
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| 4. |
- Thelin, Jonas, et al.
(författare)
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Implant size and fixation mode strongly influence tissue reactions in the CNS
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. e16267-
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Tidskriftsartikel (refereegranskat)abstract
- The function of chronic brain machine interfaces depends on stable electrical contact between neurons and electrodes. A key step in the development of interfaces is therefore to identify implant configurations that minimize adverse long-term tissue reactions. To this end, we here characterized the separate and combined effects of implant size and fixation mode at 6 and 12 weeks post implantation in rat (n = 24) cerebral cortex. Neurons and activated microglia and astrocytes were visualized using NeuN, ED1 and GFAP immunofluorescence microscopy, respectively. The contributions of individual experimental variables to the tissue response were quantified. Implants tethered to the skull caused larger tissue reactions than un-tethered implants. Small diameter (50 mu m) implants elicited smaller tissue reactions and resulted in the survival of larger numbers of neurons than did large diameter (200 mu m) implants. In addition, tethering resulted in an oval-shaped cavity, with a cross-section area larger than that of the implant itself, and in marked changes in morphology and organization of neurons in the region closest to the tissue interface. Most importantly, for implants that were both large diameter and tethered, glia activation was still ongoing 12 weeks after implantation, as indicated by an increase in GFAP staining between week 6 and 12, while this pattern was not observed for un-tethered, small diameter implants. Our findings therefore clearly indicate that the combined small diameter, un-tethered implants cause the smallest tissue reactions.
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| 5. |
- Zhang, Mengliang, et al.
(författare)
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Hindlimb motor responses to unilateral brain injury : spinal cord encoding and left-right asymmetry
- 2020
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a unilateral lesion to the cerebellum produced postural asymmetry with ipsilateral hindlimb flexion that was retained after complete spinal cord transection. Here we demonstrate that hindlimb postural asymmetry in rats is induced by a unilateral injury of the hindlimb sensorimotor cortex, and characterize this phenomenon as a model of spinal neuroplasticity underlying asymmetric motor deficits. After cortical lesion, the asymmetry was developed due to the contralesional hindlimb flexion and persisted after decerebration and complete spinal cord transection. The asymmetry induced by the left-side brain injury was eliminated by bilateral lumbar dorsal rhizotomy, but surprisingly, the asymmetry after the right-side brain lesion was resistant to deafferentation. Pancuronium, a curare-mimetic muscle relaxant, abolished the asymmetry after the right-side lesion suggesting its dependence on the efferent drive. The contra- and ipsilesional hindlimbs displayed different musculo-articular resistance to stretch after the left but not right-side injury. The nociceptive withdrawal reflexes evoked by electrical stimulation and recorded with EMG technique were different between the left and right hindlimbs in the spinalized decerebrate rats. On this asymmetric background, a brain injury resulted in greater reflex activation on the contra- versus ipsilesional side; the difference between the limbs was higher after the right-side brain lesion. The unilateral brain injury modified expression of neuroplasticity genes analysed as readout of plastic changes, as well as robustly impaired coordination of their expression within and between the ipsi- and contralesional halves of lumbar spinal cord; the effects were more pronounced after the left side compared to the right-side injury. Our data suggest that changes in the hindlimb posture, resistance to stretch and nociceptive withdrawal reflexes are encoded by neuroplastic processes in lumbar spinal circuits induced by a unilateral brain injury. Two mechanisms, one dependent on and one independent of afferent input may mediate asymmetric hindlimb motor responses. The latter, deafferentation resistant mechanism may be based on sustained muscle contractions which often occur in patients with central lesions and which are not evoked by afferent stimulation. The unusual feature of these mechanisms is their lateralization in the spinal cord.
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| 6. |
- Ejserholm, Fredrik, et al.
(författare)
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A polymer neural probe with tunable flexibility
- 2013
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Ingår i: 2013 6th International IEEE/EMBS Conference on Neural Engineering (NER). - 1948-3546. - 9781467319690 ; , s. 691-694
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Konferensbidrag (refereegranskat)abstract
- A novel polymeric material, off stoichiometry thiol-ene-epoxy (OSTE+), has been evaluated for the fabrication of neural implants. OSTE+ is easily photo-structurable and exhibits mechanical properties suitable for stable implantation of the probe into brain tissue, while being sufficiently soft at physiological temperatures to reduce living tissue damage. The facile processing of OSTE+ allows use in applications where SU-8 or polyimide currently are the materials of choice. Uniquely, OSTE+ has a Young’s modulus of 1.9 GPa at 10 °C decreasing almost two orders of magnitude to 30 MPa at 40 °C, which can be compared to the Young’s modulus of 2.1 GPa for SU-8. We show a probe, with nine gold electrode sites, implanted into 0.5% agar at 40 °C using active cooling during the implantation.
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| 7. |
- Forni, Matilde, et al.
(författare)
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3D microelectrode cluster and stimulation paradigm yield powerful analgesia without noticeable adverse effects
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:41
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Tidskriftsartikel (refereegranskat)abstract
- The lack of satisfactory treatment for persistent pain profoundly impairs the quality of life for many patients. Stimulation of brainstem pain control systems can trigger powerful analgesia, but their complex network organization frequently prevents separation of analgesia from side effects. To overcome this long-standing challenge, we developed a biocompatible gelatin-embedded cluster of ultrathin microelectrodes that enables fine-tuned, high-definition three-dimensional stimulation in periaqueductal gray/dorsal raphe nucleus in awake rats. Analgesia was assessed from both motor reactions and intracortical signals, corresponding to pain-related signals in humans. We could select an individual-specific subset of microelectrodes in each animal that reliably provided strong pain inhibition during normal and hyperalgesia conditions, without noticeable behavioral side effects. Gait, spontaneous cortical activity at rest, and cortical tactile responses were minimally affected, indicating a highly selective action. In conclusion, our developed biocompatible microelectrode cluster and stimulation paradigm reliably enabled powerful, fine-tuned, and selective analgesia without noticeable side effects.
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| 8. |
- Bakalkin, Georgy, et al.
(författare)
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Unilateral traumatic brain injury of the left and right hemisphere produces the left hindlimb response in rats
- 2021
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 239:7, s. 2221-2232
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury and stroke result in hemiplegia, hemiparesis, and asymmetry in posture. The effects are mostly contralateral; however, ipsilesional deficits may also develop. We here examined whether ablation brain injury and controlled cortical impact (CCI), a rat model of clinical focal traumatic brain injury, both centered over the left or right sensorimotor cortex, induced hindlimb postural asymmetry (HL-PA) with contralesional or ipsilesional limb flexion. The contralesional hindlimb was flexed after left or right side ablation injury. In contrast, both the left and right CCI unexpectedly produced HL-PA with flexion on left side. The flexion persisted after complete spinal cord transection suggesting that CCI triggered neuroplastic processes in lumbar neural circuits enabling asymmetric muscle contraction. Left limb flexion was exhibited under pentobarbital anesthesia. However, under ketamine anesthesia, the body of the left and right CCI rats bent laterally in the coronal plane to the ipsilesional side suggesting that the left and right injury engaged mirror-symmetrical motor pathways. Thus, the effects of the left and right CCI on HL-PA were not mirror-symmetrical in contrast to those of the ablation brain injury, and to the left and right CCI produced body bending. Ipsilateral effects of the left CCI on HL-PA may be mediated by a lateralized motor pathway that is not affected by the left ablation injury. Alternatively, the left-side-specific neurohormonal mechanism that signals from injured brain to spinal cord may be activated by both the left and right CCI but not by ablation injury.
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| 9. |
- Tornero, Daniel, et al.
(författare)
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Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli
- 2017
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 140:3, s. 692-706
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channel-rhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex.
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| 10. |
- Ljungquist, Bengt, et al.
(författare)
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A Novel Framework for Storage, Analysis and Integration through Mediation of Large-scale Electrophysiological Data
- 2011
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Ingår i: 2011 5TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER). - 1948-3546. ; , s. 203-207
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Konferensbidrag (refereegranskat)abstract
- We present a framework based on object orientation with novel principles for how to store, analyze and integrate electrophysiological data. These principles are: (I) Using a Decorator pattern for storing analysis data in an object model, (II) using a Core Classes data structure for integration through mediation in a service bus architecture, and (III) choosing the single unit as the finest structure of the object model. With these principles, we address the problems of (1) how to relate the analysis data to the original electrophysiological data by utilizing design patterns, (2) how to integrate data from different data sources, both at application and organization levels and (3) avoiding performance problems by choosing the correct level of object granularity for the data.
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