Frontiers in neuroscience
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Frontiers in neuroscience · Jan 2019
ReviewMechanisms of Immune Activation by c9orf72-Expansions in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with overlapping pathomechanisms, neurobehavioral features, and genetic etiologies. Individuals diagnosed with either disorder exhibit symptoms within a clinical spectrum. Symptoms of ALS involve neuromusculature deficits, reflecting upper and lower motor neurodegeneration, while the primary clinical features of FTD are behavioral and cognitive impairments, reflecting frontotemporal lobar degeneration. ⋯ This review highlights the current understanding of the cellular, proteomic and genetic substrates through which G4C2 HREs may elicit detrimental immune activity, facilitating region-specific neurodegeneration in C9orf72 mediated ALS/FTD. We in particular emphasize interactions between intracellular pathways induced by C9orf72 expansions and innate immune inflammasome complexes, intracellular receptors responsible for eliciting inflammation in response to cellular stress. A further understanding of the intricate, reciprocal relationship between the cellular and molecular pathologies resulting from C9orf72 HREs and immune activation may yield novel therapeutics for ALS/FTD, which currently have limited treatment strategies.
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Frontiers in neuroscience · Jan 2019
ReviewVagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations.
Over the last several decades, vagus nerve stimulation (VNS) has evolved from a treatment for select neuropsychiatric disorders to one that holds promise in treating numerous inflammatory conditions. Growing interest has focused on the use of VNS for other indications, such as heart failure, rheumatoid arthritis, inflammatory bowel disease, ischemic stroke, and traumatic brain injury. ⋯ In this review, we discuss these important considerations and how a combination of clinically relevant stimulation parameters can be used to achieve beneficial therapeutic results in pre-clinical studies of sub-acute to chronic VNS, and provide a practical guide for performing this work in rodent models. Finally, by integrating clinical and pre-clinical research, we present indeterminate issues as opportunities for future research.
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Frontiers in neuroscience · Jan 2019
ReviewTargeted Vagus Nerve Stimulation for Rehabilitation After Stroke.
Stroke is a leading cause of disability worldwide, and in approximately 60% of individuals, upper limb deficits persist 6 months after stroke. These deficits adversely affect the functional use of the upper limb and restrict participation in day to day activities. An important goal of stroke rehabilitation is to improve the quality of life by enhancing functional independence and participation in activities. ⋯ In both studies, VNS paired with rehabilitation improved motor deficits compared to rehabilitation alone. The trials provided support for a 120-patient pivotal study designed to evaluate the efficacy of paired VNS therapy in individuals with chronic ischemic stroke. This manuscript will discuss the neurobiological rationale for VNS therapy, provide an in-depth discussion of both animal and human studies of VNS therapy for stroke, and outline the challenges and opportunities for the future use of VNS therapy.
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Frontiers in neuroscience · Jan 2019
Single Sessions of High-Definition Transcranial Direct Current Stimulation Do Not Alter Lower Extremity Biomechanical or Corticomotor Response Variables Post-stroke.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate cortical activity. However, measured effects on clinically relevant assessments have been inconsistent, possibly due to the non-focal dispersion of current from traditional two electrode configurations. High-definition (HD)-tDCS uses a small array of electrodes (N = 5) to improve targeted current delivery. ⋯ A single session of anodal or cathodal HD-tDCS delivered to a standardized ipsilesional area of the motor cortex does not appear to alter gait kinematics or corticomotor response post-stroke. Repeated sessions and individualized delivery of HD-tDCS may be required to induce beneficial plastic effects. Contralesional stimulation should also be investigated due to the altered interactions between the cerebral hemispheres post-stroke.
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Frontiers in neuroscience · Jan 2019
Differential tDCS and tACS Effects on Working Memory-Related Neural Activity and Resting-State Connectivity.
Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) entail capability to modulate human brain dynamics and cognition. However, the comparability of these approaches at the level of large-scale functional networks has not been thoroughly investigated. In this study, 44 subjects were randomly assigned to receive sham (N = 15), tDCS (N = 15), or tACS (N = 14). ⋯ In sum, tDCS and tACS modulate fMRI-derived network dynamics differently. However, both effects seem to focus on DMN regions and the WM network-DMN shift, which are highly affected in aging and disease. Thus, albeit exploratory and needing further replication with larger samples, our results might provide a refined understanding of how the DMN functioning can be externally modulated through commonly used non-invasive brain stimulation techniques, which may be of eventual clinical relevance.