Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
| Autor: | Brian R. Noga, Francisco J. Sanchez, James D. Guest, Yohjans Nunez-Gomez, Juan P. Solano, Pedro Pinheiro Saraiva, Andrea J. Santamaria, Ioan Opris, Francisco D. Benavides, Luz M. Villamil, Stephano J. Chang |
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| Rok vydání: | 2020 |
| Předmět: |
Deep brain stimulation
Swine medicine.medical_treatment Deep Brain Stimulation Biophysics Stimulation Neurosciences. Biological psychiatry. Neuropsychiatry 050105 experimental psychology Midbrain 03 medical and health sciences 0302 clinical medicine Gait (human) Mesencephalon Medicine Animals Humans 0501 psychology and cognitive sciences Spinal cord injury Gait Pedunculopontine nucleus Pig business.industry General Neuroscience Parkinsonism 05 social sciences Parkinson Disease medicine.disease Neuromodulation (medicine) Cuneiform nucleus Neurology (clinical) business Mesencephalic locomotor region Defensive behavior Neuroscience 030217 neurology & neurosurgery Locomotion RC321-571 |
| Zdroj: | Brain Stimulation, Vol 14, Iss 3, Pp 467-476 (2021) |
| ISSN: | 1876-4754 |
| Popis: | Background Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson’s disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness. Objective We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait. Methods We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill. Results MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals. Conclusion Pigs appear to have an MLR and can be used to model neuromodulation of this gait-promoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson’s disease, spinal cord injury, or stroke. |
| Databáze: | OpenAIRE |
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