Experimental neurology
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Experimental neurology · Sep 2013
Anatomical correlates of recovery in single pellet reaching in spinal cord injured rats.
Modeling spinal cord injury (SCI) in animals is challenging because an appropriate combination of lesion location, lesion severity and behavioral testing is essential to analyze recovery of motor function. For particular tests such as single pellet reaching, the contribution of individual descending tracts to recovery has been investigated using specific tract ablation or graded lesions. However, it has not been established whether single pellet reaching is sufficiently sensitive for assessing the efficacy of treatments for cervical SCI (e.g., one of the currently most successful treatment approaches: rehabilitative training). ⋯ The DLQ lesion likely strikes a balance between tissue sparing and functional impairment and is, therefore, best suited to maximize the potential to observe treatment effects of plasticity-promoting treatments using single pellet reaching. Because of the specific lesion size that is necessary to observe treatment effects, the single pellet skilled reaching task can be considered a stringent behavioral test and therefore may be useful for predicting translational success of potential treatments. However, due to the variability in the success rate, the labor-intensive nature, and the limited usefulness to test functional outcome of a wide range of lesion severities, we are hesitant to continue to use single pellet reaching to assess the effectiveness of currently available treatments for cervical SCI.
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Over the past 70years, diffuse axonal injury (DAI) has emerged as one of the most common and important pathological features of traumatic brain injury (TBI). Axons in the white matter appear to be especially vulnerable to injury due to the mechanical loading of the brain during TBI. As such, DAI has been found in all severities of TBI and may represent a key pathologic substrate of mild TBI (concussion). ⋯ In addition, recent evidence suggests that TBI may induce long-term neurodegenerative processes, such as insidiously progressive axonal pathology. Indeed, axonal degeneration has been found to continue even years after injury in humans, and appears to play a role in the development of Alzheimer's disease-like pathological changes. Here we review the current understanding of DAI as a uniquely mechanical injury, its histopathological identification, and its acute and chronic pathogenesis following TBI.
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Experimental neurology · Jul 2013
ReviewAdaptive deep brain stimulation (aDBS) controlled by local field potential oscillations.
Despite their proven efficacy in treating neurological disorders, especially Parkinson's disease, deep brain stimulation (DBS) systems could be further optimized to maximize treatment benefits. In particular, because current open-loop DBS strategies based on fixed stimulation settings leave the typical parkinsonian motor fluctuations and rapid symptom variations partly uncontrolled, research has for several years focused on developing novel "closed-loop" or "adaptive" DBS (aDBS) systems. aDBS consists of a simple closed-loop model designed to measure and analyze a control variable reflecting the patient's clinical condition to elaborate new stimulation settings and send them to an "intelligent" implanted stimulator. The major problem in developing an aDBS system is choosing the ideal control variable for feedback. Here we review current evidence on the advantages of neurosignal-controlled aDBS that uses local field potentials (LFPs) as a control variable, and describe the technology already available to create new aDBS systems, and the potential benefits of aDBS for patients with Parkinson's disease.
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Experimental neurology · Jul 2013
Spatial extent of β oscillatory activity in and between the subthalamic nucleus and substantia nigra pars reticulata of Parkinson's disease patients.
Parkinson's disease (PD) is accompanied by a significant amount of β-band (11 Hz-30 Hz) neuronal and local field potential (LFP) oscillatory activity in the subthalamic nucleus (STN). Previous studies have shown significant coherence between neuronal firing and LFPs at β frequencies at sites separated by ~1 mm and that the magnitude of β oscillatory LFP activity and coherence are greatly reduced following levodopa administration. However, these data have been collected from large DBS contact electrodes or pairs of microelectrodes in proximity to each other and so it is not clear whether all regions of STN are synchronized. ⋯ We confirmed previous reports of a progressive attenuation in β power as electrodes were driven from dorsal to ventral STN and into SNr. Furthermore, we found significant β-LFP coherence across the dorsoventral extent of STN. Detailed analysis suggested that at least some of the ventral STN and SNr beta activity was locally generated rather than arising from volume conduction from dorsal STN and thus suggests that β oscillations synchronize both the input and output nuclei of the basal ganglia.
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There is increased interest in neurostimulation as a treatment for drug-resistant epilepsy. Two large pivotal trials have recently been completed, one using bilateral anterior thalamic stimulation and another employing closed loop responsive therapy of the brain. These are potential additions to the therapeutic options for neurostimulation in addition to already approved vagus nerve stimulation. This review will address the principles of the various types of neurostimulation, the results of the pivotal trials and the important considerations for interpreting the results of these trials which differ from trials of antiepileptic drugs.